Review ArticleGenus Tinospora EthnopharmacologyPhytochemistry and Pharmacology

Sensen Chi1 Gaimei She1 Dan Han1 Weihua Wang2 Zhao Liu2 and Bin Liu1

1School of Chinese Pharmacy Beijing University of Chinese Medicine Beijing 100102 China2National Institute of Metrology Beijing 100013 China

Correspondence should be addressed to Bin Liu liubinyn67163com

Received 3 May 2016 Revised 10 July 2016 Accepted 13 July 2016

Academic Editor Nunziatina De Tommasi

Copyright copy 2016 Sensen Chi et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The genusTinospora includes 34 species inwhich several herbswere used as traditionalmedicines by indigenous groups throughoutthe tropical and subtropical parts of Asia Africa and Australia The extensive literature survey revealed Tinospora species to be agroup of important medicinal plants used for the ethnomedical treatment of colds headaches pharyngitis fever diarrhea oralulcer diabetes digestive disorder and rheumatoid arthritis Indian ethnopharmacological data points to the therapeutic potentialof the T cordifolia for the treatment of diabetic conditions While Tinospora species are confusing in individual ingredients andtheirmechanisms of action the ethnopharmacological history of those plants indicated that they exhibit antidiabetic antioxidationantitumor anti-inflammation antimicrobial antiosteoporosis and immunostimulation activities While the clinical applicationsin modern medicine are lacking convincing evidence and support this review is aimed at summarizing the current knowledge ofthe traditional uses phytochemistry biological activities and toxicities of the genus Tinospora to reveal its therapeutic potentialsand gaps offering opportunities for future researches

1 Introduction

The genus Tinospora (Menispermaceae) 34 species includedis a large glabrous deciduous climbing shrub [1] The specieshave been widely distributed throughout the tropical andsubtropical parts of Asia Africa and Australia At present6 species and 2 varieties are found in China in which Thainanensis and T guangxiensis Lo as endemic species aremainly distributed in Guangxi and Hainan T sinensis andT capillipes are officially listed in the 2015 edition of theChinese Pharmacopoeia (中华人民共和国药典) with theChinese names ldquoKuan Jin Tengrdquo (宽筋藤) and ldquoJin Guo Lanrdquo(金果榄) respectively [2] Those herbs in genus Tinosporaare mostly heat-clearing and detoxifying (清热解毒) Andthey are commonly used as domestic folk medicine for thetreatment of colds headaches pharyngitis fever diarrheaoral ulcer digestive disorder and rheumatoid arthritis Forinstance Indian Ayurveda usually employs T cordifolia intreatment for diabetes Its obvious antidiabetic propertiesattract modern researchesrsquo attention [3] T sinensis is themajor composition in a famous traditional formula ldquoSi Wei

Zang Mu Xiangrdquo powder (四味藏木香) used for thetreatment of wind-heat disease (风热病) and deficiency-heat syndrome (虚热证) [3 4] This family is a richsource of terpenes and alkaloids the ongoing explorationfor bioactive constituents also revealed the presence of C

6-

C3derivatives polysaccharides and other components with

exact structures Modern pharmacological researches andclinical practices demonstrated thatTinospora species possessa wide spectrum of activities including antidiabetic [3]antioxidation [5 6] antitumor [7 8] anti-inflammation [910] antimicrobial [11] antiosteoporosis [12] and immunos-timulation effect [13] In clinic genus Tinospora is commonlyused to protect and support the immune system to preventupper respiratory infections to lower oral ulcer to treatdiabetes to be an adjunctive therapy in cancer and toprotect the liverHowever a systematic review of these studieshas not been performed to date This paper summarizedthe research achievements of the medicine plants in genusTinospora ranging from clinical studies to phytochemistryand pharmacology areas It is expected that such a paperwould on one hand serve as an available database for future

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2016 Article ID 9232593 32 pageshttpdxdoiorg10115520169232593

2 Evidence-Based Complementary and Alternative Medicine

researches and on the other hand enable experts in the fieldto determine if the research on genus Tinospora is on properpath

2 Traditional Uses and Ethnopharmacology

Those species in this genus have traditionally been usedas therapeutic remedies (Table 1) On the basis of ourinvestigations they are clinically applied for the treatmentof fever and parasitic diseases mouth skin respiratory andurinary tract infections oral ulcer and diabetes in additionto being an adjunctive therapy in cancer and to protectingthe liver [14ndash22]The official record about species in China ofgenus Tinospora appeared in ldquoBencao Gangmu Shiyirdquo [ZhaoXuemin Qing dynasty year 1765 Bencao Gangmu Shiyi (本草纲目拾遗)] It is recorded that T capillipes is primarilyused on the therapy of dysentery diarrhea and abdominalpain with heat toxic furuncle ulcer and sore throat It is alsothe traditional medicine of Mao Dong and Yao minorityof China being applied to the treatment of acute laryn-gopharyngitis tonsillitis gastroenteritis and bacillary dysen-tery [23 24] Earlier ldquoJingzhu Bencaordquo [DimaersdotDanzengPengCuo Qing dynasty year 1745 Jingzhu Bencao (晶珠本草)] which is an ancient Chinese Tibetan medicinalencyclopedia recorded that T sinensis has been used forrelieving rigidity of muscle and activating collaterals (舒筋活络) and alleviating pain (活血止痛) Its tropismof taste is Xinand Ku and in the liver channel (味辛苦主肝经) ChineseDai Medicine (傣医药学) claimed that T sinensis could alsoregulate and invigorate the blood (调补气血) and tranquilizethe mind (镇心安神) It is clinically used to treat palpitation(心悸) and improve the frail physique (体弱无力) ThailandLanna Medicine (泰国兰纳医药学) claimed that T sinensiswas more inclined to clear the heat and cool off the fire (清热降火) inside the body thus usually clinically applied torelieve high fever and ameliorate the symptoms of diabetes[15ndash26] In India T cordifolia referred to as Guduchi (plantwhich protects from diseases Sanskrit) has been describedin ancient text books of Ayurveda including Sushrut Samhitaand Charak Samhita [27] According to Ayurveda T cordi-folia itself possesses a bitter pungent and astringent tasteThe bitter taste is said to improve metabolic activity evenat a cellular level It is documented to treat gastrointestinaldiseases including dyspepsia flatulence gastritis jaundicediarrhea splenomegaly and hemorrhoids It has a role in thetreatment of metabolic disorders such as diabetes and kidneydisorders and it is currently more inclined to be a researchfocus It is prescribed for intermittent fevers infective condi-tions urinary disorders skin diseases and eye diseases Incombination with other herbs it is commonly used as aningredient to treat gout and rheumatoid arthritis And thewell-ground whole plant is applied to fractures Moreover Tcordifolia shows healthy effects due to its various nutritiouscompounds and is considered as a general tonic [27 28] Thediverse significant ethnomedicinal properties possessed bythis genus could be the basis for further researches to inves-tigate the phytochemical and pharmacological aspects of thisgenus

3 Pharmacological Activities

Scientific studies all over the world for over 50 years haverevealed much insight into the pharmacological functionsof Tinospora Crude extracts and pure compounds fromTinospora plants have shown significant antidiabetic antioxi-dant antitumor anti-inflammatory antimicrobial antiosteo-porosis and immunostimulation properties In this sectionbiological activities of the active compounds andmixtures onthe species are highlighted

31 Antioxidant Activity Natural plants used in traditionalChinese medicine have antioxidant effects through differ-ent mechanisms including DPPH radical scavenging assaysuperoxide anion scavenging assay hydroxyl radical scav-enging assay and ABTS radical scavenging method [35]On a comparative basis T sinensis and T cordifolia weretested to have equal antioxidant activities [36] Ilaiyarajaand Khanum evaluated the antioxidant potential of differentsolvent extracts of leaf and stem of T cordifolia Scavengingeffects on DPPH ABTS radical hydroxyl radical and ferricreducing antioxidant power (FRAP) were found to be highestin methanolic extract of leaf and ethyl acetate extract of stemIt is because the polarity of solvent showed a greater effecton the ordered structure of the active phenolic components[5] The study on leaf and stem powders of T cordifoliafollowed by DPPH method found that the leaf extractpowder has higher retention of antioxidant activity thanthe stemrsquos [37] As early as 1998 Cavin et al isolated andidentified three compoundsN-cis-feruloyltyramine N-trans-feruloyltyramine and secoisolariciresinol from T crispaThese ingredients proved to bemore active than the syntheticantioxidant butylhydroxytoluene (BHT) [38] Another inves-tigation showed that the essential oil obtained from leaves ofT cordifolia demonstrated strong DPPH radical scavengingactivity with IC

50values of 25 plusmn 03 120583gmL The components

identified in essential oil include alcohols (321) phe-nols (166) aldehydes (162) fatty acids (157) alkanes(83) esters (32) terpenes (12) and others (48)[39] The work carried on hitherto rarely studied fruit of Tcordifolia showed that it is also rich in antioxidant propertieswith the IC

50being 468 120583gg and EC

50being 1472 120583gg yet

the effect of the fruit is not comparable to the other parts[5 6] These active components and mixtures could serve asvaluable indications to develop them as possible antioxidantdrugs for the treatment and the prevention of diseases Moreimportantly oxidative stress is proved to be critical for thepathogenesis of diabetes mellitus Clarification of antioxidantissues could help to understand the treatment of diabetesmellitus and promote the development of antidiabetic naturalproducts [40]

32 Antidiabetic Activity Many pharmacologic studies haveclearly confirmed the antidiabetic effects of genus Tinosporain vivo Compared with other commonly seen antidiabeticdrugs T crispa and T cordifolia exhibit more powerfulantidiabetic activity and they have been widely used inAsia and Africa as a remedy mainly in regard to type 2diabetes mellitus [41] Ruan et al explored the hypoglycemic

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Classic prescriptions of genus Tinospora in traditional and clinical usages

Species Preparationnameformulation Main compositions Medicinal uses References

T sinensis Decoction

Liquidambar formosanaHanceSperanskia tuberculata (Bge) Baill

Angelica sinensis (Oliv) DielsClematis chinensis OsbeckBombyx mori Linnaeus

Cinnamomum cassia PreslAchyranthes bidentata Bl

Spatholobus suberectus DunnAconitum kusnezoffii ReichbAtractylodes lancea (Thunb)

Asarum heterotropoides Fr Schmidtvarmandshuricum (Maxim) Kitag

Knee joint osteoarthritis [14]

T sinensis Qutan Tongluo Tang (祛痰通络汤)

Arca subcrenata LischkeArisaema cum Bile

Drynaria fortune (Kunze) J SmDipsacus asper Wall ex HenryAngelica sinensis (Oliv) Diels

Chaenomeles speciosa (Sweet) NakaiEucommia ulmoides OlivPaeonia lactiflora Pall

Corydalis yanhusuoW T WangAngelica pubescensMaxim F biserrata

Shan et YuanAkebia quinata (Thunb) Decne

Lumbar disc herniation [15]

T sinensis Huoxue Shujin Xunxifang(活血舒筋熏洗方)

Clematis chinensis OsbeckSparganium stoloniferum Buch-Ham

Curcuma phaeocaulis ValUncaria rhynchophylla (Miq) Miq ex

HavilCarthamus tinctorius LSalvia miltiorrhiza Bge

Ligusticum chuanxiong HortAchyranthes bidentata Bl

Aconitum kusnezoffii ReichbAucklandia lappa Decne

Ankylosis [16]

T sinensis Sisheng Tang (四生汤)

Rheum palmatum LClematis chinensis Osbeck

Speranskia tuberculata (Bge) BaillChaenomeles speciosa (Sweet) NakaiArisaema erubescens (Wall) Schott

Aconitum kusnezoffii ReichbAconitum carmichaelii Debx

Fracture [17]

T sinensis Fumigation

Lycopodium japonicumThunbSperanskia tuberculata (Bge) Baill

Spatholobus suberectus DunnPrunus persica (L) BatschCarthamus tinctorius L

Angelica sinensis (Oliv) DielsLigusticum chuanxiong Hort

Ankle fracture [18]

T sinensis Decoction mdash Visceral leishmaniasis [19]

T capillipes Jinguo Heji (金果合剂)

Scrophularia ningpoensisHenslPlatycodon grandiflorum (Jacq) A DC

Glycyrrhiza uralensis FischOphiopogon japonicas (Lf) Ker Gawl

Apis cerana Fabricius

Pharyngitis [20]

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Continued

Species Preparationnameformulation Main compositions Medicinal uses References

T capillipes Soaking solution mdash Infusion phlebitis [21]

T capillipes Powder mdash

Upper respiratory tractinfection

Acute tonsillitisLaryngopharyngitisAcute gastroenteritis

PneumoniaTracheitis

[22]

T cordifolia DecoctionBerberis aristata

Terminalia chebulaZingiber officinale

Experimental amoebic liverabscess [29]

T cordifolia Decoction

Phyllanthus niruriTerminalia belericaTerminalia chebulaPhyllanthus emblica

Carbon tetrachloride inducedhepatotoxicity [30]

T cordifolia Decoction mdash Diabetic foot ulcers [31]T cordifolia Decoction mdash Allergic rhinitis [32]

T cordifolia Decoction mdashObstructive jaundice

tuberculosis sepsis breastcancer

[27]

T cordifolia Decoction

Boerhavia diffusaBerberis aristata

Terminalia chebulaZingiber officinale

Entamoeba histolytica [33]

T cordifolia DecoctionZingiber officinaleWithania somniferaTribulus terrestris

Rheumatoid arthritis [34]

effects of borapetoside A mediated through both the insulin-dependent and the insulin-independent pathways Theyfound that borapetoside A was able to increase the glucoseutilization in peripheral tissues to reduce the hepatic glu-coneogenesis and to activate the insulin signaling pathwayComparison of the structures of three borapetosides from Tcrispa clearly suggested that the C-8 stereochemistry plays akey role in hypoglycemic effect since the active borapetosidesA and C possess 8R-chirality while the inactive borapetosideB possesses 8S-chirality The location of glycoside at C-3 for borapetoside A (while it is C-6 for borapetoside C)and the formation of lactone between C-4 and C-6 forborapetoside A could account for the different potency inhypoglycemic action for these two compounds [42 43]Borapetol B is another antidiabetic active property from Tcrispa By evaluating the blood glucose levels and stimulationof insulin secretion in normoglycemic control Wistar anddiabetic Goto-Kakizaki rats Lokman et al provided evidencethat oral administration of borapetol B has antidiabeticproperties mainly due to its stimulation of insulin release[42 44] Antidiabetic potential of T cordifolia stem is alsowell proven [3 45 46] Patel and Mishra chose sucroseand maltose as substrates to study the enzyme kineticsand the respective Michaelis-Menten constant meanwhilemaximal velocity values were estimated Three isoquinolinealkaloids from T cordifolia namely jatrorrhizine palmatineand magnoflorine showed IC

50value as sucrase inhibitor to

be 3625 2346 and 98 120583gmL and maltase inhibitor to be2205 3842 and 760120583gmL Furthermore the increase inplasma glucose level in in vivo studies conducted on rats wassignificantly suppressed (119875 lt 001) by all the three alkaloidsat 20mgkg bwt [47] Kannadhasan and Venkataramanreported that the presence of antioxidant potentials in extractof T cordifolia was a potent healer in ameliorating diabeteslike tissue damage in vivo [48] It is perfectly consistentwith the report that T cordifolia has a significant (119875 lt005) effect in ameliorating the specific parameters towardnormal in diabetic animals and it has a level of efficacythat is considerably good compared to standard drug insulin[49] These experimental results further enrich previousunderstanding of the antidiabetic activity of genus Tinosporaand provide scientific data of therapeutic efficacy againstdiabetes mellitus

33 Immunostimulatory Activity Several Tinospora specieshave effects on humoral immunity cellular immunity andnonspecific immunity Polysaccharide a kind of naturalmacromolecule has widespread occurrence in biologicalbodies and has many kinds of biological activities whichplays an important role in regulating immune system [50]Polysaccharides in Tinospora represent a structurally diverseclass of macromolecules and this structural variability canprofoundly affect their cell-type specificity and their bio-logical activity in B cells Previous studies documented that

Evidence-Based Complementary and Alternative Medicine 5

phytogenic polysaccharides could regulate animalsrsquo immunesystem by combining tomembrane receptors of immune cellsand initiating the special signaling pathways This includesstimulating the secretion or proliferation of macrophagesTB lymphocytes and natural killer (NK) cells modulatingthe release of cytokines promoting the production of anti-bodies and activating the complement system [51] (14)-120572-D-Glucan (120572-DG) is a novel immune stimulatory drug fromT cordifolia It exhibited macrophages activating abilitiesthrough TLR6 signaling and NF-120581B activation mechanismfollowed by the production of cytokines and chemokinesIt can also differentially modulate cytokine production inthe spleen and lung on endotoxaemic juvenile rats In thelung 120572-DG treatment reduced anti-inflammatory cytokineconcentrations of IL-1120573 by 30 IL-6 by 43 IFN-120574 by46 and IL-10 by 31 compared to endotoxaemia Inthe spleen 120572-DG treatment decreased the ratio of IL-1120573to IL-10 by 55 [52ndash54] Further data showed that 120572-DG led to significant tachycardia without causing hypoten-sion Accompanied by significant reduction in the bloodhemoglobin and hematocrit concentrations the effect did notchange respiratory variable andor plasma concentration ofinflammatory cytokines in anaesthetized rats [55] G1-4A anarabinogalactan polysaccharide from T cordifolia is a well-characterized immunomodulatory in both in vitro and in vivosystems Administration (125mgkg body weight) of G1-4Ato mice led to splenomegaly and an increase in the numbersof T cells B cells and macrophages This increase in spleencellularity was due to in vivo proliferation of lymphocytesand upregulation of antiapoptotic genes G1-4A inducedproliferation of B cells was completely inhibited by PI3Kinhibitor Ly294002 mTOR inhibitor rapamycin and NF-120581Binhibitor plumbagin Meanwhile Akt ERK and JNK wereactivated by G1-4A which finally resulted in the activationof IKK degradation of I120581B-120572 and translocation of NF-120581Bto the nucleus [56ndash58] In the humoral and cell-mediatedimmune response T cordifolia preparation enhanced meanhemagglutination antibody titre and reactive oxygen levelagainst various pathogens [59ndash61] Polar fractions of Tcordifolia stem at a dose of 40mgkg body weight promotedthe nonspecific host and defence of the immune systemdirectly acted on peritonealmacrophages [13] T crispa crudeextract significantly stimulated RAW 2647 cell viability (119875 le005) and intracellular INF-120574 IL-6 and IL-8 expressionsStudy of LC-MS showed that the immunomodulatory activecompounds are cordioside quercetin eicosenoic acid andboldine [62] Other reports indicated that it is the syn-ergistic effect of immunomodulatory active compounds ingenus Tinospora that contributed to the immunomodulatoryactivity [61 63] As mentioned above polysaccharides ingenus Tinospora play a key role in the immunostimulatoryactivityThe characteristics of polysaccharides which includebackbone structure branching degree molecular weight andthree spiral structures affected the activity of immunityBy activating the inherent and acquired immune systemto produce antitumor immunity the immunomodulatoryactivity could also contribute to the tumor immunotherapy[64]

34 Antitumor Activity Feature chemical components ofTinospora clerodane diterpenes showed apparent cytotoxicactivity against tumor cells [65] Nowadays the antitumoreffect of the Tinospora species has been widely studied in vivoand in vitro The mechanisms of the antitumor activity ofTinospora species aremainly concentrated on the cytotoxicityand cell apoptosis induced Epoxy clerodane diterpenes wereevaluated for the activity against diethylnitrosamine-inducedhepatocyte carcinoma the results concluded that they kickin blocking carcinogen metabolic activation and enhancingcarcinogen detoxification [66 67] Aqueous ethanolic ingre-dients of T cordifolia reduced cell proliferation in dose-dependent manner and induced differentiation in C

6glioma

cells The cell proliferation inhibition was in part mediatedthrough accumulation in S phase and G2M arrest withconcomitant suppression of p21 expression and inhibition ofcyclin-dependent kinase activity [68] Treatment of hexaneextract fraction of T cordifolia on Ehrlich ascites tumorbearing animals resulted in growth inhibition and inductionof apoptosis in a dose-dependent manner in vivo The mech-anism of action was caspase-3 dependent which caused anuclear localization of apoptosis meanwhile the formation ofapoptotic bodies nuclear condensation typical DNA ladderand decreased cell number and ascites volume [7] More andPai observed that treatment with T cordifolia and LPS ofmacrophage cell line J774A1 followed the enhanced NADH-oxidase NADPH-oxidase and myeloperoxidase productionas compared to medium alone [69] According to recentstudies alkaloids chemical constituents from plants havethe characteristics of better antitumor activity high effectgood tolerance and slight side effect [70] Alkaloid especiallypalmatine from T cordifolia significantly decreased tumorsize number and the activity of serum enzyme in DMBAinduced skin cancer mice The alkaloid could also contributeto the reduction of glutathione (GSH) superoxide dismutase(SOD) and catalase however it increased DNA damage [71]The activation of macrophages is another pathway for antitu-mor activity (14)-120572-D-Glucan andG1-4A are immunologicalactive polysaccharides from T cordifolia Treatment withG1-4A on a murine lymphoma model increased T cellallostimulatory activity and secretion of IL-12 and TNF120572 bybone marrow derived dendritic cells leading to the lysis oftarget tumor cells in vitro Polysaccharides can also activatemacrophages NK cells APDs and T and B lymphocytesto enhance antitumor immunity concerned with secretionof cytokines activation of the complement system induc-tion of apoptosis of tumor cells and intracellular signaltransduction so as to achieve the tumor inhibitory effectby regulations of the immune system [56 72] Sonaimuthuet al identified taxol producing endophytic fungus F cul-morum SVJM072 from medicinal plant of T cordifoliaFurther research showed that the fungal taxol had strongactivity against human cancer cell lines by MTT assay andM tuberculosis H37Rv by Radiometric Bactec 460 assaywhich could serve as an excellent alternative source anda genetically engineered species for anticancer compounds[73]

6 Evidence-Based Complementary and Alternative Medicine

35 Anti-Inflammatory and Antimicrobial Activity Inflam-mation is a pathologic condition that includes a wide rangeof diseases such as rheumatic and immune-mediated con-ditions diabetes and cardiovascular accident If the processof inflammatory response cannot end normally when celldebris and pathogens were cleared the biological defenceresponse will become causative factor Medicinal plants andtheir secondary metabolites are progressively used in thetreatment of diseases as a complementary medicine [7475] Palmatine and jatrorrhizine mainly separated fromtubers of T capillipes and T cordifolia have widely beenapplied in clinic owing to their comparatively broad spectruminhibitory activity With the EC

50values ranged from 00348

to 08356 gL and 00240 to 08649 gL respectively palma-tine and jatrorrhizine exhibited inhibition against many plantpathogens The two alkaloids vary only in the substituents ofposition 3 of A ring in terms of the chemical structure Theeffectiveness of protoberberine was related to the ammoniumN linked at position 7 of aromatic ring in the chemicalstructure and the inhibitory activity of protoberberine alka-loids altered by the different substituents in A and D rings[76] The ethanol extract of T smilacina showed inhibitoryactivities on COX-1 COX-2 5-LO and PA

2with the IC

50

values of 635 812 921 and 305 120583gmL respectively [9]Considerable decrease in the levels of iNOS COX-2 andICAM-1 resulted in the reduced release of proinflammatorymediators like TNF-120572 IL-4 NO and IgE [10] An insightinto the antimicrobial activity of the ethanolic extracts of Tcordifolia indicated that the secondary metabolites exhibitedhigh inhibitory activity against clinically isolated S aureusand K pneumoniae [11] It is noteworthy that inductionof embryogenic callus of T cordifolia with the presence ofadditional compoundswas able to inhibit bothGram-positiveand Gram-negative organisms [77] All in all inflammationis a complex and multifaceted problem so the treatmentof inflammation is not a one-dimensional remedy Theanti-inflammation of herbal medicine belonging to genusTinospora has a favorable applied perspective with the helpof modification in structure it may assist in reaching amultidimensional therapeutic approach to inflammation inthe future [78]

36 Antiosteoporosis Activity During recent years researchesin traditional Chinese medicine for the treatment of osteo-porosis are increasing especially in the research and ther-apeutic application using compound medicine and exter-nal medicine and some progress has been made [79] Tcapillipes and T cordifolia were reported to induce alkalinephosphatase activity in mesenchymal stem cells based onecdysone compounds At the dosage of 25120583gmL ethanolicextracts of T cordifolia stimulated the growth of osteoblastsincreased the differentiation of cells into osteoblastic lineageand increased the mineralization of bone-like matrix onboth the osteoblast model systems Previously Gao et alnoted that the stem extracts of T cordifolia in ovariec-tomized rats significantly prevented the bone loss in ratsinduced by ovariectomy without causing proliferative effectsin uterus and mammary gland [80 81] In addition thepresence of high concentration of calcium in T cordifolia

made it a natural cure for osteoporosis [12] Moreover singleor synergistic formulations of T cordifolia with Zingiberofficinale have been used in ancient India medicinal systemto treat rheumatoid arthritis [34] However the morbidityof osteoporosis has been linked to several factors such asage gender and races In order to get a good outcomeof osteoporosis treatment both surgical management andpharmacological treatment are necessary

37 OtherTherapeutic Activities What ismoreTinospora hasbeen investigated to exert other pharmacological activitiesCordifolioside Amainly isolated in T cordifolia has a poten-tial in vivo radioprotective effect and in vitro cytoprotectiveactivity [82] The impressive radioprotective efficacy may berelated to the attenuation of radiation induced decrease ofadherence and spreading increase of IL-1120573 and GM-CSFlevels and reduction of apoptosis [83]The radiosensitizationby T cordifoliamay be also due to depletion of GSH andGSTaccompanied by elevated levels of LPx and DNA damage oftumor cells [84]

Ethanolic extract of T sinensis exhibited an appreciableactivity against promastigotes (IC

50376 plusmn 62 120583gmL) and

intracellular amastigotes (IC50298 plusmn 34 120583gmL) In ham-

sters it resulted in 762 plusmn 92 inhibition at 500mgkgday times5 oral dose levels [19ndash24] T cordifolia (100mgkg bwtfor 15 days daily) used in combination with cisplatin in Ldonovani infected BALBc mice selectively induced Th1 typeof immune response It was concluded by the enhanced levelsof IFN-c and IL-2 with moderate decline of Th2 specificcytokines IL-4 and IL-10 [85]

The least polar alkaloid from T crispa columbamineshowed strong acetyl-cholinesterase inhibitory activitywith IC

504810 120583molL The structure-activity relationships

derived from these results suggested that the quaternarynitrogen in the skeleton has some effect but that a high degreeof methoxylation is more important for acetylcholinesteraseinhibition [86]

T cordifolia ethanol extract exhibited significant neuro-protection by increasing the dopamine levels (196 plusmn 020and 245 plusmn 040 ngmg of protein) and complex I activity(7714plusmn 089 and 7850plusmn 096 nmolminmg of protein) at 200and 400mgkg respectively [87] Combination of ethanolicextracts of T cordifolia B monnieri and E alsinoides inequal proportion provided synergistic nootropic effect onscopolamine induced amnesia in rats [88]

4 Chemical Constituents

The chemical constituents of Tinospora have long been thepursued objectives of the researchers and multiple classesof chemical constituents have been isolated and reportedWithin these compounds diterpenoids are the most domi-nant constituent found in the currently studied species in thisgenus Up to now 223 compounds have been isolated fromgenus Tinospora including terpenoids alkaloids steroidsC6-C3derivatives and polysaccharides as well as other

components The compounds list and their structures areshown in Table 2 and Figure 1

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

2 Evidence-Based Complementary and Alternative Medicine

researches and on the other hand enable experts in the fieldto determine if the research on genus Tinospora is on properpath

2 Traditional Uses and Ethnopharmacology

Those species in this genus have traditionally been usedas therapeutic remedies (Table 1) On the basis of ourinvestigations they are clinically applied for the treatmentof fever and parasitic diseases mouth skin respiratory andurinary tract infections oral ulcer and diabetes in additionto being an adjunctive therapy in cancer and to protectingthe liver [14ndash22]The official record about species in China ofgenus Tinospora appeared in ldquoBencao Gangmu Shiyirdquo [ZhaoXuemin Qing dynasty year 1765 Bencao Gangmu Shiyi (本草纲目拾遗)] It is recorded that T capillipes is primarilyused on the therapy of dysentery diarrhea and abdominalpain with heat toxic furuncle ulcer and sore throat It is alsothe traditional medicine of Mao Dong and Yao minorityof China being applied to the treatment of acute laryn-gopharyngitis tonsillitis gastroenteritis and bacillary dysen-tery [23 24] Earlier ldquoJingzhu Bencaordquo [DimaersdotDanzengPengCuo Qing dynasty year 1745 Jingzhu Bencao (晶珠本草)] which is an ancient Chinese Tibetan medicinalencyclopedia recorded that T sinensis has been used forrelieving rigidity of muscle and activating collaterals (舒筋活络) and alleviating pain (活血止痛) Its tropismof taste is Xinand Ku and in the liver channel (味辛苦主肝经) ChineseDai Medicine (傣医药学) claimed that T sinensis could alsoregulate and invigorate the blood (调补气血) and tranquilizethe mind (镇心安神) It is clinically used to treat palpitation(心悸) and improve the frail physique (体弱无力) ThailandLanna Medicine (泰国兰纳医药学) claimed that T sinensiswas more inclined to clear the heat and cool off the fire (清热降火) inside the body thus usually clinically applied torelieve high fever and ameliorate the symptoms of diabetes[15ndash26] In India T cordifolia referred to as Guduchi (plantwhich protects from diseases Sanskrit) has been describedin ancient text books of Ayurveda including Sushrut Samhitaand Charak Samhita [27] According to Ayurveda T cordi-folia itself possesses a bitter pungent and astringent tasteThe bitter taste is said to improve metabolic activity evenat a cellular level It is documented to treat gastrointestinaldiseases including dyspepsia flatulence gastritis jaundicediarrhea splenomegaly and hemorrhoids It has a role in thetreatment of metabolic disorders such as diabetes and kidneydisorders and it is currently more inclined to be a researchfocus It is prescribed for intermittent fevers infective condi-tions urinary disorders skin diseases and eye diseases Incombination with other herbs it is commonly used as aningredient to treat gout and rheumatoid arthritis And thewell-ground whole plant is applied to fractures Moreover Tcordifolia shows healthy effects due to its various nutritiouscompounds and is considered as a general tonic [27 28] Thediverse significant ethnomedicinal properties possessed bythis genus could be the basis for further researches to inves-tigate the phytochemical and pharmacological aspects of thisgenus

3 Pharmacological Activities

Scientific studies all over the world for over 50 years haverevealed much insight into the pharmacological functionsof Tinospora Crude extracts and pure compounds fromTinospora plants have shown significant antidiabetic antioxi-dant antitumor anti-inflammatory antimicrobial antiosteo-porosis and immunostimulation properties In this sectionbiological activities of the active compounds andmixtures onthe species are highlighted

31 Antioxidant Activity Natural plants used in traditionalChinese medicine have antioxidant effects through differ-ent mechanisms including DPPH radical scavenging assaysuperoxide anion scavenging assay hydroxyl radical scav-enging assay and ABTS radical scavenging method [35]On a comparative basis T sinensis and T cordifolia weretested to have equal antioxidant activities [36] Ilaiyarajaand Khanum evaluated the antioxidant potential of differentsolvent extracts of leaf and stem of T cordifolia Scavengingeffects on DPPH ABTS radical hydroxyl radical and ferricreducing antioxidant power (FRAP) were found to be highestin methanolic extract of leaf and ethyl acetate extract of stemIt is because the polarity of solvent showed a greater effecton the ordered structure of the active phenolic components[5] The study on leaf and stem powders of T cordifoliafollowed by DPPH method found that the leaf extractpowder has higher retention of antioxidant activity thanthe stemrsquos [37] As early as 1998 Cavin et al isolated andidentified three compoundsN-cis-feruloyltyramine N-trans-feruloyltyramine and secoisolariciresinol from T crispaThese ingredients proved to bemore active than the syntheticantioxidant butylhydroxytoluene (BHT) [38] Another inves-tigation showed that the essential oil obtained from leaves ofT cordifolia demonstrated strong DPPH radical scavengingactivity with IC

50values of 25 plusmn 03 120583gmL The components

identified in essential oil include alcohols (321) phe-nols (166) aldehydes (162) fatty acids (157) alkanes(83) esters (32) terpenes (12) and others (48)[39] The work carried on hitherto rarely studied fruit of Tcordifolia showed that it is also rich in antioxidant propertieswith the IC

50being 468 120583gg and EC

50being 1472 120583gg yet

the effect of the fruit is not comparable to the other parts[5 6] These active components and mixtures could serve asvaluable indications to develop them as possible antioxidantdrugs for the treatment and the prevention of diseases Moreimportantly oxidative stress is proved to be critical for thepathogenesis of diabetes mellitus Clarification of antioxidantissues could help to understand the treatment of diabetesmellitus and promote the development of antidiabetic naturalproducts [40]

32 Antidiabetic Activity Many pharmacologic studies haveclearly confirmed the antidiabetic effects of genus Tinosporain vivo Compared with other commonly seen antidiabeticdrugs T crispa and T cordifolia exhibit more powerfulantidiabetic activity and they have been widely used inAsia and Africa as a remedy mainly in regard to type 2diabetes mellitus [41] Ruan et al explored the hypoglycemic

Evidence-Based Complementary and Alternative Medicine 3

Table 1 Classic prescriptions of genus Tinospora in traditional and clinical usages

Species Preparationnameformulation Main compositions Medicinal uses References

T sinensis Decoction

Liquidambar formosanaHanceSperanskia tuberculata (Bge) Baill

Angelica sinensis (Oliv) DielsClematis chinensis OsbeckBombyx mori Linnaeus

Cinnamomum cassia PreslAchyranthes bidentata Bl

Spatholobus suberectus DunnAconitum kusnezoffii ReichbAtractylodes lancea (Thunb)

Asarum heterotropoides Fr Schmidtvarmandshuricum (Maxim) Kitag

Knee joint osteoarthritis [14]

T sinensis Qutan Tongluo Tang (祛痰通络汤)

Arca subcrenata LischkeArisaema cum Bile

Drynaria fortune (Kunze) J SmDipsacus asper Wall ex HenryAngelica sinensis (Oliv) Diels

Chaenomeles speciosa (Sweet) NakaiEucommia ulmoides OlivPaeonia lactiflora Pall

Corydalis yanhusuoW T WangAngelica pubescensMaxim F biserrata

Shan et YuanAkebia quinata (Thunb) Decne

Lumbar disc herniation [15]

T sinensis Huoxue Shujin Xunxifang(活血舒筋熏洗方)

Clematis chinensis OsbeckSparganium stoloniferum Buch-Ham

Curcuma phaeocaulis ValUncaria rhynchophylla (Miq) Miq ex

HavilCarthamus tinctorius LSalvia miltiorrhiza Bge

Ligusticum chuanxiong HortAchyranthes bidentata Bl

Aconitum kusnezoffii ReichbAucklandia lappa Decne

Ankylosis [16]

T sinensis Sisheng Tang (四生汤)

Rheum palmatum LClematis chinensis Osbeck

Speranskia tuberculata (Bge) BaillChaenomeles speciosa (Sweet) NakaiArisaema erubescens (Wall) Schott

Aconitum kusnezoffii ReichbAconitum carmichaelii Debx

Fracture [17]

T sinensis Fumigation

Lycopodium japonicumThunbSperanskia tuberculata (Bge) Baill

Spatholobus suberectus DunnPrunus persica (L) BatschCarthamus tinctorius L

Angelica sinensis (Oliv) DielsLigusticum chuanxiong Hort

Ankle fracture [18]

T sinensis Decoction mdash Visceral leishmaniasis [19]

T capillipes Jinguo Heji (金果合剂)

Scrophularia ningpoensisHenslPlatycodon grandiflorum (Jacq) A DC

Glycyrrhiza uralensis FischOphiopogon japonicas (Lf) Ker Gawl

Apis cerana Fabricius

Pharyngitis [20]

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Continued

Species Preparationnameformulation Main compositions Medicinal uses References

T capillipes Soaking solution mdash Infusion phlebitis [21]

T capillipes Powder mdash

Upper respiratory tractinfection

Acute tonsillitisLaryngopharyngitisAcute gastroenteritis

PneumoniaTracheitis

[22]

T cordifolia DecoctionBerberis aristata

Terminalia chebulaZingiber officinale

Experimental amoebic liverabscess [29]

T cordifolia Decoction

Phyllanthus niruriTerminalia belericaTerminalia chebulaPhyllanthus emblica

Carbon tetrachloride inducedhepatotoxicity [30]

T cordifolia Decoction mdash Diabetic foot ulcers [31]T cordifolia Decoction mdash Allergic rhinitis [32]

T cordifolia Decoction mdashObstructive jaundice

tuberculosis sepsis breastcancer

[27]

T cordifolia Decoction

Boerhavia diffusaBerberis aristata

Terminalia chebulaZingiber officinale

Entamoeba histolytica [33]

T cordifolia DecoctionZingiber officinaleWithania somniferaTribulus terrestris

Rheumatoid arthritis [34]

effects of borapetoside A mediated through both the insulin-dependent and the insulin-independent pathways Theyfound that borapetoside A was able to increase the glucoseutilization in peripheral tissues to reduce the hepatic glu-coneogenesis and to activate the insulin signaling pathwayComparison of the structures of three borapetosides from Tcrispa clearly suggested that the C-8 stereochemistry plays akey role in hypoglycemic effect since the active borapetosidesA and C possess 8R-chirality while the inactive borapetosideB possesses 8S-chirality The location of glycoside at C-3 for borapetoside A (while it is C-6 for borapetoside C)and the formation of lactone between C-4 and C-6 forborapetoside A could account for the different potency inhypoglycemic action for these two compounds [42 43]Borapetol B is another antidiabetic active property from Tcrispa By evaluating the blood glucose levels and stimulationof insulin secretion in normoglycemic control Wistar anddiabetic Goto-Kakizaki rats Lokman et al provided evidencethat oral administration of borapetol B has antidiabeticproperties mainly due to its stimulation of insulin release[42 44] Antidiabetic potential of T cordifolia stem is alsowell proven [3 45 46] Patel and Mishra chose sucroseand maltose as substrates to study the enzyme kineticsand the respective Michaelis-Menten constant meanwhilemaximal velocity values were estimated Three isoquinolinealkaloids from T cordifolia namely jatrorrhizine palmatineand magnoflorine showed IC

50value as sucrase inhibitor to

be 3625 2346 and 98 120583gmL and maltase inhibitor to be2205 3842 and 760120583gmL Furthermore the increase inplasma glucose level in in vivo studies conducted on rats wassignificantly suppressed (119875 lt 001) by all the three alkaloidsat 20mgkg bwt [47] Kannadhasan and Venkataramanreported that the presence of antioxidant potentials in extractof T cordifolia was a potent healer in ameliorating diabeteslike tissue damage in vivo [48] It is perfectly consistentwith the report that T cordifolia has a significant (119875 lt005) effect in ameliorating the specific parameters towardnormal in diabetic animals and it has a level of efficacythat is considerably good compared to standard drug insulin[49] These experimental results further enrich previousunderstanding of the antidiabetic activity of genus Tinosporaand provide scientific data of therapeutic efficacy againstdiabetes mellitus

33 Immunostimulatory Activity Several Tinospora specieshave effects on humoral immunity cellular immunity andnonspecific immunity Polysaccharide a kind of naturalmacromolecule has widespread occurrence in biologicalbodies and has many kinds of biological activities whichplays an important role in regulating immune system [50]Polysaccharides in Tinospora represent a structurally diverseclass of macromolecules and this structural variability canprofoundly affect their cell-type specificity and their bio-logical activity in B cells Previous studies documented that

Evidence-Based Complementary and Alternative Medicine 5

phytogenic polysaccharides could regulate animalsrsquo immunesystem by combining tomembrane receptors of immune cellsand initiating the special signaling pathways This includesstimulating the secretion or proliferation of macrophagesTB lymphocytes and natural killer (NK) cells modulatingthe release of cytokines promoting the production of anti-bodies and activating the complement system [51] (14)-120572-D-Glucan (120572-DG) is a novel immune stimulatory drug fromT cordifolia It exhibited macrophages activating abilitiesthrough TLR6 signaling and NF-120581B activation mechanismfollowed by the production of cytokines and chemokinesIt can also differentially modulate cytokine production inthe spleen and lung on endotoxaemic juvenile rats In thelung 120572-DG treatment reduced anti-inflammatory cytokineconcentrations of IL-1120573 by 30 IL-6 by 43 IFN-120574 by46 and IL-10 by 31 compared to endotoxaemia Inthe spleen 120572-DG treatment decreased the ratio of IL-1120573to IL-10 by 55 [52ndash54] Further data showed that 120572-DG led to significant tachycardia without causing hypoten-sion Accompanied by significant reduction in the bloodhemoglobin and hematocrit concentrations the effect did notchange respiratory variable andor plasma concentration ofinflammatory cytokines in anaesthetized rats [55] G1-4A anarabinogalactan polysaccharide from T cordifolia is a well-characterized immunomodulatory in both in vitro and in vivosystems Administration (125mgkg body weight) of G1-4Ato mice led to splenomegaly and an increase in the numbersof T cells B cells and macrophages This increase in spleencellularity was due to in vivo proliferation of lymphocytesand upregulation of antiapoptotic genes G1-4A inducedproliferation of B cells was completely inhibited by PI3Kinhibitor Ly294002 mTOR inhibitor rapamycin and NF-120581Binhibitor plumbagin Meanwhile Akt ERK and JNK wereactivated by G1-4A which finally resulted in the activationof IKK degradation of I120581B-120572 and translocation of NF-120581Bto the nucleus [56ndash58] In the humoral and cell-mediatedimmune response T cordifolia preparation enhanced meanhemagglutination antibody titre and reactive oxygen levelagainst various pathogens [59ndash61] Polar fractions of Tcordifolia stem at a dose of 40mgkg body weight promotedthe nonspecific host and defence of the immune systemdirectly acted on peritonealmacrophages [13] T crispa crudeextract significantly stimulated RAW 2647 cell viability (119875 le005) and intracellular INF-120574 IL-6 and IL-8 expressionsStudy of LC-MS showed that the immunomodulatory activecompounds are cordioside quercetin eicosenoic acid andboldine [62] Other reports indicated that it is the syn-ergistic effect of immunomodulatory active compounds ingenus Tinospora that contributed to the immunomodulatoryactivity [61 63] As mentioned above polysaccharides ingenus Tinospora play a key role in the immunostimulatoryactivityThe characteristics of polysaccharides which includebackbone structure branching degree molecular weight andthree spiral structures affected the activity of immunityBy activating the inherent and acquired immune systemto produce antitumor immunity the immunomodulatoryactivity could also contribute to the tumor immunotherapy[64]

34 Antitumor Activity Feature chemical components ofTinospora clerodane diterpenes showed apparent cytotoxicactivity against tumor cells [65] Nowadays the antitumoreffect of the Tinospora species has been widely studied in vivoand in vitro The mechanisms of the antitumor activity ofTinospora species aremainly concentrated on the cytotoxicityand cell apoptosis induced Epoxy clerodane diterpenes wereevaluated for the activity against diethylnitrosamine-inducedhepatocyte carcinoma the results concluded that they kickin blocking carcinogen metabolic activation and enhancingcarcinogen detoxification [66 67] Aqueous ethanolic ingre-dients of T cordifolia reduced cell proliferation in dose-dependent manner and induced differentiation in C

6glioma

cells The cell proliferation inhibition was in part mediatedthrough accumulation in S phase and G2M arrest withconcomitant suppression of p21 expression and inhibition ofcyclin-dependent kinase activity [68] Treatment of hexaneextract fraction of T cordifolia on Ehrlich ascites tumorbearing animals resulted in growth inhibition and inductionof apoptosis in a dose-dependent manner in vivo The mech-anism of action was caspase-3 dependent which caused anuclear localization of apoptosis meanwhile the formation ofapoptotic bodies nuclear condensation typical DNA ladderand decreased cell number and ascites volume [7] More andPai observed that treatment with T cordifolia and LPS ofmacrophage cell line J774A1 followed the enhanced NADH-oxidase NADPH-oxidase and myeloperoxidase productionas compared to medium alone [69] According to recentstudies alkaloids chemical constituents from plants havethe characteristics of better antitumor activity high effectgood tolerance and slight side effect [70] Alkaloid especiallypalmatine from T cordifolia significantly decreased tumorsize number and the activity of serum enzyme in DMBAinduced skin cancer mice The alkaloid could also contributeto the reduction of glutathione (GSH) superoxide dismutase(SOD) and catalase however it increased DNA damage [71]The activation of macrophages is another pathway for antitu-mor activity (14)-120572-D-Glucan andG1-4A are immunologicalactive polysaccharides from T cordifolia Treatment withG1-4A on a murine lymphoma model increased T cellallostimulatory activity and secretion of IL-12 and TNF120572 bybone marrow derived dendritic cells leading to the lysis oftarget tumor cells in vitro Polysaccharides can also activatemacrophages NK cells APDs and T and B lymphocytesto enhance antitumor immunity concerned with secretionof cytokines activation of the complement system induc-tion of apoptosis of tumor cells and intracellular signaltransduction so as to achieve the tumor inhibitory effectby regulations of the immune system [56 72] Sonaimuthuet al identified taxol producing endophytic fungus F cul-morum SVJM072 from medicinal plant of T cordifoliaFurther research showed that the fungal taxol had strongactivity against human cancer cell lines by MTT assay andM tuberculosis H37Rv by Radiometric Bactec 460 assaywhich could serve as an excellent alternative source anda genetically engineered species for anticancer compounds[73]

6 Evidence-Based Complementary and Alternative Medicine

35 Anti-Inflammatory and Antimicrobial Activity Inflam-mation is a pathologic condition that includes a wide rangeof diseases such as rheumatic and immune-mediated con-ditions diabetes and cardiovascular accident If the processof inflammatory response cannot end normally when celldebris and pathogens were cleared the biological defenceresponse will become causative factor Medicinal plants andtheir secondary metabolites are progressively used in thetreatment of diseases as a complementary medicine [7475] Palmatine and jatrorrhizine mainly separated fromtubers of T capillipes and T cordifolia have widely beenapplied in clinic owing to their comparatively broad spectruminhibitory activity With the EC

50values ranged from 00348

to 08356 gL and 00240 to 08649 gL respectively palma-tine and jatrorrhizine exhibited inhibition against many plantpathogens The two alkaloids vary only in the substituents ofposition 3 of A ring in terms of the chemical structure Theeffectiveness of protoberberine was related to the ammoniumN linked at position 7 of aromatic ring in the chemicalstructure and the inhibitory activity of protoberberine alka-loids altered by the different substituents in A and D rings[76] The ethanol extract of T smilacina showed inhibitoryactivities on COX-1 COX-2 5-LO and PA

2with the IC

50

values of 635 812 921 and 305 120583gmL respectively [9]Considerable decrease in the levels of iNOS COX-2 andICAM-1 resulted in the reduced release of proinflammatorymediators like TNF-120572 IL-4 NO and IgE [10] An insightinto the antimicrobial activity of the ethanolic extracts of Tcordifolia indicated that the secondary metabolites exhibitedhigh inhibitory activity against clinically isolated S aureusand K pneumoniae [11] It is noteworthy that inductionof embryogenic callus of T cordifolia with the presence ofadditional compoundswas able to inhibit bothGram-positiveand Gram-negative organisms [77] All in all inflammationis a complex and multifaceted problem so the treatmentof inflammation is not a one-dimensional remedy Theanti-inflammation of herbal medicine belonging to genusTinospora has a favorable applied perspective with the helpof modification in structure it may assist in reaching amultidimensional therapeutic approach to inflammation inthe future [78]

36 Antiosteoporosis Activity During recent years researchesin traditional Chinese medicine for the treatment of osteo-porosis are increasing especially in the research and ther-apeutic application using compound medicine and exter-nal medicine and some progress has been made [79] Tcapillipes and T cordifolia were reported to induce alkalinephosphatase activity in mesenchymal stem cells based onecdysone compounds At the dosage of 25120583gmL ethanolicextracts of T cordifolia stimulated the growth of osteoblastsincreased the differentiation of cells into osteoblastic lineageand increased the mineralization of bone-like matrix onboth the osteoblast model systems Previously Gao et alnoted that the stem extracts of T cordifolia in ovariec-tomized rats significantly prevented the bone loss in ratsinduced by ovariectomy without causing proliferative effectsin uterus and mammary gland [80 81] In addition thepresence of high concentration of calcium in T cordifolia

made it a natural cure for osteoporosis [12] Moreover singleor synergistic formulations of T cordifolia with Zingiberofficinale have been used in ancient India medicinal systemto treat rheumatoid arthritis [34] However the morbidityof osteoporosis has been linked to several factors such asage gender and races In order to get a good outcomeof osteoporosis treatment both surgical management andpharmacological treatment are necessary

37 OtherTherapeutic Activities What ismoreTinospora hasbeen investigated to exert other pharmacological activitiesCordifolioside Amainly isolated in T cordifolia has a poten-tial in vivo radioprotective effect and in vitro cytoprotectiveactivity [82] The impressive radioprotective efficacy may berelated to the attenuation of radiation induced decrease ofadherence and spreading increase of IL-1120573 and GM-CSFlevels and reduction of apoptosis [83]The radiosensitizationby T cordifoliamay be also due to depletion of GSH andGSTaccompanied by elevated levels of LPx and DNA damage oftumor cells [84]

Ethanolic extract of T sinensis exhibited an appreciableactivity against promastigotes (IC

50376 plusmn 62 120583gmL) and

intracellular amastigotes (IC50298 plusmn 34 120583gmL) In ham-

sters it resulted in 762 plusmn 92 inhibition at 500mgkgday times5 oral dose levels [19ndash24] T cordifolia (100mgkg bwtfor 15 days daily) used in combination with cisplatin in Ldonovani infected BALBc mice selectively induced Th1 typeof immune response It was concluded by the enhanced levelsof IFN-c and IL-2 with moderate decline of Th2 specificcytokines IL-4 and IL-10 [85]

The least polar alkaloid from T crispa columbamineshowed strong acetyl-cholinesterase inhibitory activitywith IC

504810 120583molL The structure-activity relationships

derived from these results suggested that the quaternarynitrogen in the skeleton has some effect but that a high degreeof methoxylation is more important for acetylcholinesteraseinhibition [86]

T cordifolia ethanol extract exhibited significant neuro-protection by increasing the dopamine levels (196 plusmn 020and 245 plusmn 040 ngmg of protein) and complex I activity(7714plusmn 089 and 7850plusmn 096 nmolminmg of protein) at 200and 400mgkg respectively [87] Combination of ethanolicextracts of T cordifolia B monnieri and E alsinoides inequal proportion provided synergistic nootropic effect onscopolamine induced amnesia in rats [88]

4 Chemical Constituents

The chemical constituents of Tinospora have long been thepursued objectives of the researchers and multiple classesof chemical constituents have been isolated and reportedWithin these compounds diterpenoids are the most domi-nant constituent found in the currently studied species in thisgenus Up to now 223 compounds have been isolated fromgenus Tinospora including terpenoids alkaloids steroidsC6-C3derivatives and polysaccharides as well as other

components The compounds list and their structures areshown in Table 2 and Figure 1

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

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Evidence-Based Complementary and Alternative Medicine

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Evidence-Based Complementary and Alternative Medicine 3

Table 1 Classic prescriptions of genus Tinospora in traditional and clinical usages

Species Preparationnameformulation Main compositions Medicinal uses References

T sinensis Decoction

Liquidambar formosanaHanceSperanskia tuberculata (Bge) Baill

Angelica sinensis (Oliv) DielsClematis chinensis OsbeckBombyx mori Linnaeus

Cinnamomum cassia PreslAchyranthes bidentata Bl

Spatholobus suberectus DunnAconitum kusnezoffii ReichbAtractylodes lancea (Thunb)

Asarum heterotropoides Fr Schmidtvarmandshuricum (Maxim) Kitag

Knee joint osteoarthritis [14]

T sinensis Qutan Tongluo Tang (祛痰通络汤)

Arca subcrenata LischkeArisaema cum Bile

Drynaria fortune (Kunze) J SmDipsacus asper Wall ex HenryAngelica sinensis (Oliv) Diels

Chaenomeles speciosa (Sweet) NakaiEucommia ulmoides OlivPaeonia lactiflora Pall

Corydalis yanhusuoW T WangAngelica pubescensMaxim F biserrata

Shan et YuanAkebia quinata (Thunb) Decne

Lumbar disc herniation [15]

T sinensis Huoxue Shujin Xunxifang(活血舒筋熏洗方)

Clematis chinensis OsbeckSparganium stoloniferum Buch-Ham

Curcuma phaeocaulis ValUncaria rhynchophylla (Miq) Miq ex

HavilCarthamus tinctorius LSalvia miltiorrhiza Bge

Ligusticum chuanxiong HortAchyranthes bidentata Bl

Aconitum kusnezoffii ReichbAucklandia lappa Decne

Ankylosis [16]

T sinensis Sisheng Tang (四生汤)

Rheum palmatum LClematis chinensis Osbeck

Speranskia tuberculata (Bge) BaillChaenomeles speciosa (Sweet) NakaiArisaema erubescens (Wall) Schott

Aconitum kusnezoffii ReichbAconitum carmichaelii Debx

Fracture [17]

T sinensis Fumigation

Lycopodium japonicumThunbSperanskia tuberculata (Bge) Baill

Spatholobus suberectus DunnPrunus persica (L) BatschCarthamus tinctorius L

Angelica sinensis (Oliv) DielsLigusticum chuanxiong Hort

Ankle fracture [18]

T sinensis Decoction mdash Visceral leishmaniasis [19]

T capillipes Jinguo Heji (金果合剂)

Scrophularia ningpoensisHenslPlatycodon grandiflorum (Jacq) A DC

Glycyrrhiza uralensis FischOphiopogon japonicas (Lf) Ker Gawl

Apis cerana Fabricius

Pharyngitis [20]

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Continued

Species Preparationnameformulation Main compositions Medicinal uses References

T capillipes Soaking solution mdash Infusion phlebitis [21]

T capillipes Powder mdash

Upper respiratory tractinfection

Acute tonsillitisLaryngopharyngitisAcute gastroenteritis

PneumoniaTracheitis

[22]

T cordifolia DecoctionBerberis aristata

Terminalia chebulaZingiber officinale

Experimental amoebic liverabscess [29]

T cordifolia Decoction

Phyllanthus niruriTerminalia belericaTerminalia chebulaPhyllanthus emblica

Carbon tetrachloride inducedhepatotoxicity [30]

T cordifolia Decoction mdash Diabetic foot ulcers [31]T cordifolia Decoction mdash Allergic rhinitis [32]

T cordifolia Decoction mdashObstructive jaundice

tuberculosis sepsis breastcancer

[27]

T cordifolia Decoction

Boerhavia diffusaBerberis aristata

Terminalia chebulaZingiber officinale

Entamoeba histolytica [33]

T cordifolia DecoctionZingiber officinaleWithania somniferaTribulus terrestris

Rheumatoid arthritis [34]

effects of borapetoside A mediated through both the insulin-dependent and the insulin-independent pathways Theyfound that borapetoside A was able to increase the glucoseutilization in peripheral tissues to reduce the hepatic glu-coneogenesis and to activate the insulin signaling pathwayComparison of the structures of three borapetosides from Tcrispa clearly suggested that the C-8 stereochemistry plays akey role in hypoglycemic effect since the active borapetosidesA and C possess 8R-chirality while the inactive borapetosideB possesses 8S-chirality The location of glycoside at C-3 for borapetoside A (while it is C-6 for borapetoside C)and the formation of lactone between C-4 and C-6 forborapetoside A could account for the different potency inhypoglycemic action for these two compounds [42 43]Borapetol B is another antidiabetic active property from Tcrispa By evaluating the blood glucose levels and stimulationof insulin secretion in normoglycemic control Wistar anddiabetic Goto-Kakizaki rats Lokman et al provided evidencethat oral administration of borapetol B has antidiabeticproperties mainly due to its stimulation of insulin release[42 44] Antidiabetic potential of T cordifolia stem is alsowell proven [3 45 46] Patel and Mishra chose sucroseand maltose as substrates to study the enzyme kineticsand the respective Michaelis-Menten constant meanwhilemaximal velocity values were estimated Three isoquinolinealkaloids from T cordifolia namely jatrorrhizine palmatineand magnoflorine showed IC

50value as sucrase inhibitor to

be 3625 2346 and 98 120583gmL and maltase inhibitor to be2205 3842 and 760120583gmL Furthermore the increase inplasma glucose level in in vivo studies conducted on rats wassignificantly suppressed (119875 lt 001) by all the three alkaloidsat 20mgkg bwt [47] Kannadhasan and Venkataramanreported that the presence of antioxidant potentials in extractof T cordifolia was a potent healer in ameliorating diabeteslike tissue damage in vivo [48] It is perfectly consistentwith the report that T cordifolia has a significant (119875 lt005) effect in ameliorating the specific parameters towardnormal in diabetic animals and it has a level of efficacythat is considerably good compared to standard drug insulin[49] These experimental results further enrich previousunderstanding of the antidiabetic activity of genus Tinosporaand provide scientific data of therapeutic efficacy againstdiabetes mellitus

33 Immunostimulatory Activity Several Tinospora specieshave effects on humoral immunity cellular immunity andnonspecific immunity Polysaccharide a kind of naturalmacromolecule has widespread occurrence in biologicalbodies and has many kinds of biological activities whichplays an important role in regulating immune system [50]Polysaccharides in Tinospora represent a structurally diverseclass of macromolecules and this structural variability canprofoundly affect their cell-type specificity and their bio-logical activity in B cells Previous studies documented that

Evidence-Based Complementary and Alternative Medicine 5

phytogenic polysaccharides could regulate animalsrsquo immunesystem by combining tomembrane receptors of immune cellsand initiating the special signaling pathways This includesstimulating the secretion or proliferation of macrophagesTB lymphocytes and natural killer (NK) cells modulatingthe release of cytokines promoting the production of anti-bodies and activating the complement system [51] (14)-120572-D-Glucan (120572-DG) is a novel immune stimulatory drug fromT cordifolia It exhibited macrophages activating abilitiesthrough TLR6 signaling and NF-120581B activation mechanismfollowed by the production of cytokines and chemokinesIt can also differentially modulate cytokine production inthe spleen and lung on endotoxaemic juvenile rats In thelung 120572-DG treatment reduced anti-inflammatory cytokineconcentrations of IL-1120573 by 30 IL-6 by 43 IFN-120574 by46 and IL-10 by 31 compared to endotoxaemia Inthe spleen 120572-DG treatment decreased the ratio of IL-1120573to IL-10 by 55 [52ndash54] Further data showed that 120572-DG led to significant tachycardia without causing hypoten-sion Accompanied by significant reduction in the bloodhemoglobin and hematocrit concentrations the effect did notchange respiratory variable andor plasma concentration ofinflammatory cytokines in anaesthetized rats [55] G1-4A anarabinogalactan polysaccharide from T cordifolia is a well-characterized immunomodulatory in both in vitro and in vivosystems Administration (125mgkg body weight) of G1-4Ato mice led to splenomegaly and an increase in the numbersof T cells B cells and macrophages This increase in spleencellularity was due to in vivo proliferation of lymphocytesand upregulation of antiapoptotic genes G1-4A inducedproliferation of B cells was completely inhibited by PI3Kinhibitor Ly294002 mTOR inhibitor rapamycin and NF-120581Binhibitor plumbagin Meanwhile Akt ERK and JNK wereactivated by G1-4A which finally resulted in the activationof IKK degradation of I120581B-120572 and translocation of NF-120581Bto the nucleus [56ndash58] In the humoral and cell-mediatedimmune response T cordifolia preparation enhanced meanhemagglutination antibody titre and reactive oxygen levelagainst various pathogens [59ndash61] Polar fractions of Tcordifolia stem at a dose of 40mgkg body weight promotedthe nonspecific host and defence of the immune systemdirectly acted on peritonealmacrophages [13] T crispa crudeextract significantly stimulated RAW 2647 cell viability (119875 le005) and intracellular INF-120574 IL-6 and IL-8 expressionsStudy of LC-MS showed that the immunomodulatory activecompounds are cordioside quercetin eicosenoic acid andboldine [62] Other reports indicated that it is the syn-ergistic effect of immunomodulatory active compounds ingenus Tinospora that contributed to the immunomodulatoryactivity [61 63] As mentioned above polysaccharides ingenus Tinospora play a key role in the immunostimulatoryactivityThe characteristics of polysaccharides which includebackbone structure branching degree molecular weight andthree spiral structures affected the activity of immunityBy activating the inherent and acquired immune systemto produce antitumor immunity the immunomodulatoryactivity could also contribute to the tumor immunotherapy[64]

34 Antitumor Activity Feature chemical components ofTinospora clerodane diterpenes showed apparent cytotoxicactivity against tumor cells [65] Nowadays the antitumoreffect of the Tinospora species has been widely studied in vivoand in vitro The mechanisms of the antitumor activity ofTinospora species aremainly concentrated on the cytotoxicityand cell apoptosis induced Epoxy clerodane diterpenes wereevaluated for the activity against diethylnitrosamine-inducedhepatocyte carcinoma the results concluded that they kickin blocking carcinogen metabolic activation and enhancingcarcinogen detoxification [66 67] Aqueous ethanolic ingre-dients of T cordifolia reduced cell proliferation in dose-dependent manner and induced differentiation in C

6glioma

cells The cell proliferation inhibition was in part mediatedthrough accumulation in S phase and G2M arrest withconcomitant suppression of p21 expression and inhibition ofcyclin-dependent kinase activity [68] Treatment of hexaneextract fraction of T cordifolia on Ehrlich ascites tumorbearing animals resulted in growth inhibition and inductionof apoptosis in a dose-dependent manner in vivo The mech-anism of action was caspase-3 dependent which caused anuclear localization of apoptosis meanwhile the formation ofapoptotic bodies nuclear condensation typical DNA ladderand decreased cell number and ascites volume [7] More andPai observed that treatment with T cordifolia and LPS ofmacrophage cell line J774A1 followed the enhanced NADH-oxidase NADPH-oxidase and myeloperoxidase productionas compared to medium alone [69] According to recentstudies alkaloids chemical constituents from plants havethe characteristics of better antitumor activity high effectgood tolerance and slight side effect [70] Alkaloid especiallypalmatine from T cordifolia significantly decreased tumorsize number and the activity of serum enzyme in DMBAinduced skin cancer mice The alkaloid could also contributeto the reduction of glutathione (GSH) superoxide dismutase(SOD) and catalase however it increased DNA damage [71]The activation of macrophages is another pathway for antitu-mor activity (14)-120572-D-Glucan andG1-4A are immunologicalactive polysaccharides from T cordifolia Treatment withG1-4A on a murine lymphoma model increased T cellallostimulatory activity and secretion of IL-12 and TNF120572 bybone marrow derived dendritic cells leading to the lysis oftarget tumor cells in vitro Polysaccharides can also activatemacrophages NK cells APDs and T and B lymphocytesto enhance antitumor immunity concerned with secretionof cytokines activation of the complement system induc-tion of apoptosis of tumor cells and intracellular signaltransduction so as to achieve the tumor inhibitory effectby regulations of the immune system [56 72] Sonaimuthuet al identified taxol producing endophytic fungus F cul-morum SVJM072 from medicinal plant of T cordifoliaFurther research showed that the fungal taxol had strongactivity against human cancer cell lines by MTT assay andM tuberculosis H37Rv by Radiometric Bactec 460 assaywhich could serve as an excellent alternative source anda genetically engineered species for anticancer compounds[73]

6 Evidence-Based Complementary and Alternative Medicine

35 Anti-Inflammatory and Antimicrobial Activity Inflam-mation is a pathologic condition that includes a wide rangeof diseases such as rheumatic and immune-mediated con-ditions diabetes and cardiovascular accident If the processof inflammatory response cannot end normally when celldebris and pathogens were cleared the biological defenceresponse will become causative factor Medicinal plants andtheir secondary metabolites are progressively used in thetreatment of diseases as a complementary medicine [7475] Palmatine and jatrorrhizine mainly separated fromtubers of T capillipes and T cordifolia have widely beenapplied in clinic owing to their comparatively broad spectruminhibitory activity With the EC

50values ranged from 00348

to 08356 gL and 00240 to 08649 gL respectively palma-tine and jatrorrhizine exhibited inhibition against many plantpathogens The two alkaloids vary only in the substituents ofposition 3 of A ring in terms of the chemical structure Theeffectiveness of protoberberine was related to the ammoniumN linked at position 7 of aromatic ring in the chemicalstructure and the inhibitory activity of protoberberine alka-loids altered by the different substituents in A and D rings[76] The ethanol extract of T smilacina showed inhibitoryactivities on COX-1 COX-2 5-LO and PA

2with the IC

50

values of 635 812 921 and 305 120583gmL respectively [9]Considerable decrease in the levels of iNOS COX-2 andICAM-1 resulted in the reduced release of proinflammatorymediators like TNF-120572 IL-4 NO and IgE [10] An insightinto the antimicrobial activity of the ethanolic extracts of Tcordifolia indicated that the secondary metabolites exhibitedhigh inhibitory activity against clinically isolated S aureusand K pneumoniae [11] It is noteworthy that inductionof embryogenic callus of T cordifolia with the presence ofadditional compoundswas able to inhibit bothGram-positiveand Gram-negative organisms [77] All in all inflammationis a complex and multifaceted problem so the treatmentof inflammation is not a one-dimensional remedy Theanti-inflammation of herbal medicine belonging to genusTinospora has a favorable applied perspective with the helpof modification in structure it may assist in reaching amultidimensional therapeutic approach to inflammation inthe future [78]

36 Antiosteoporosis Activity During recent years researchesin traditional Chinese medicine for the treatment of osteo-porosis are increasing especially in the research and ther-apeutic application using compound medicine and exter-nal medicine and some progress has been made [79] Tcapillipes and T cordifolia were reported to induce alkalinephosphatase activity in mesenchymal stem cells based onecdysone compounds At the dosage of 25120583gmL ethanolicextracts of T cordifolia stimulated the growth of osteoblastsincreased the differentiation of cells into osteoblastic lineageand increased the mineralization of bone-like matrix onboth the osteoblast model systems Previously Gao et alnoted that the stem extracts of T cordifolia in ovariec-tomized rats significantly prevented the bone loss in ratsinduced by ovariectomy without causing proliferative effectsin uterus and mammary gland [80 81] In addition thepresence of high concentration of calcium in T cordifolia

made it a natural cure for osteoporosis [12] Moreover singleor synergistic formulations of T cordifolia with Zingiberofficinale have been used in ancient India medicinal systemto treat rheumatoid arthritis [34] However the morbidityof osteoporosis has been linked to several factors such asage gender and races In order to get a good outcomeof osteoporosis treatment both surgical management andpharmacological treatment are necessary

37 OtherTherapeutic Activities What ismoreTinospora hasbeen investigated to exert other pharmacological activitiesCordifolioside Amainly isolated in T cordifolia has a poten-tial in vivo radioprotective effect and in vitro cytoprotectiveactivity [82] The impressive radioprotective efficacy may berelated to the attenuation of radiation induced decrease ofadherence and spreading increase of IL-1120573 and GM-CSFlevels and reduction of apoptosis [83]The radiosensitizationby T cordifoliamay be also due to depletion of GSH andGSTaccompanied by elevated levels of LPx and DNA damage oftumor cells [84]

Ethanolic extract of T sinensis exhibited an appreciableactivity against promastigotes (IC

50376 plusmn 62 120583gmL) and

intracellular amastigotes (IC50298 plusmn 34 120583gmL) In ham-

sters it resulted in 762 plusmn 92 inhibition at 500mgkgday times5 oral dose levels [19ndash24] T cordifolia (100mgkg bwtfor 15 days daily) used in combination with cisplatin in Ldonovani infected BALBc mice selectively induced Th1 typeof immune response It was concluded by the enhanced levelsof IFN-c and IL-2 with moderate decline of Th2 specificcytokines IL-4 and IL-10 [85]

The least polar alkaloid from T crispa columbamineshowed strong acetyl-cholinesterase inhibitory activitywith IC

504810 120583molL The structure-activity relationships

derived from these results suggested that the quaternarynitrogen in the skeleton has some effect but that a high degreeof methoxylation is more important for acetylcholinesteraseinhibition [86]

T cordifolia ethanol extract exhibited significant neuro-protection by increasing the dopamine levels (196 plusmn 020and 245 plusmn 040 ngmg of protein) and complex I activity(7714plusmn 089 and 7850plusmn 096 nmolminmg of protein) at 200and 400mgkg respectively [87] Combination of ethanolicextracts of T cordifolia B monnieri and E alsinoides inequal proportion provided synergistic nootropic effect onscopolamine induced amnesia in rats [88]

4 Chemical Constituents

The chemical constituents of Tinospora have long been thepursued objectives of the researchers and multiple classesof chemical constituents have been isolated and reportedWithin these compounds diterpenoids are the most domi-nant constituent found in the currently studied species in thisgenus Up to now 223 compounds have been isolated fromgenus Tinospora including terpenoids alkaloids steroidsC6-C3derivatives and polysaccharides as well as other

components The compounds list and their structures areshown in Table 2 and Figure 1

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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OncologyJournal of

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Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

4 Evidence-Based Complementary and Alternative Medicine

Table 1 Continued

Species Preparationnameformulation Main compositions Medicinal uses References

T capillipes Soaking solution mdash Infusion phlebitis [21]

T capillipes Powder mdash

Upper respiratory tractinfection

Acute tonsillitisLaryngopharyngitisAcute gastroenteritis

PneumoniaTracheitis

[22]

T cordifolia DecoctionBerberis aristata

Terminalia chebulaZingiber officinale

Experimental amoebic liverabscess [29]

T cordifolia Decoction

Phyllanthus niruriTerminalia belericaTerminalia chebulaPhyllanthus emblica

Carbon tetrachloride inducedhepatotoxicity [30]

T cordifolia Decoction mdash Diabetic foot ulcers [31]T cordifolia Decoction mdash Allergic rhinitis [32]

T cordifolia Decoction mdashObstructive jaundice

tuberculosis sepsis breastcancer

[27]

T cordifolia Decoction

Boerhavia diffusaBerberis aristata

Terminalia chebulaZingiber officinale

Entamoeba histolytica [33]

T cordifolia DecoctionZingiber officinaleWithania somniferaTribulus terrestris

Rheumatoid arthritis [34]

effects of borapetoside A mediated through both the insulin-dependent and the insulin-independent pathways Theyfound that borapetoside A was able to increase the glucoseutilization in peripheral tissues to reduce the hepatic glu-coneogenesis and to activate the insulin signaling pathwayComparison of the structures of three borapetosides from Tcrispa clearly suggested that the C-8 stereochemistry plays akey role in hypoglycemic effect since the active borapetosidesA and C possess 8R-chirality while the inactive borapetosideB possesses 8S-chirality The location of glycoside at C-3 for borapetoside A (while it is C-6 for borapetoside C)and the formation of lactone between C-4 and C-6 forborapetoside A could account for the different potency inhypoglycemic action for these two compounds [42 43]Borapetol B is another antidiabetic active property from Tcrispa By evaluating the blood glucose levels and stimulationof insulin secretion in normoglycemic control Wistar anddiabetic Goto-Kakizaki rats Lokman et al provided evidencethat oral administration of borapetol B has antidiabeticproperties mainly due to its stimulation of insulin release[42 44] Antidiabetic potential of T cordifolia stem is alsowell proven [3 45 46] Patel and Mishra chose sucroseand maltose as substrates to study the enzyme kineticsand the respective Michaelis-Menten constant meanwhilemaximal velocity values were estimated Three isoquinolinealkaloids from T cordifolia namely jatrorrhizine palmatineand magnoflorine showed IC

50value as sucrase inhibitor to

be 3625 2346 and 98 120583gmL and maltase inhibitor to be2205 3842 and 760120583gmL Furthermore the increase inplasma glucose level in in vivo studies conducted on rats wassignificantly suppressed (119875 lt 001) by all the three alkaloidsat 20mgkg bwt [47] Kannadhasan and Venkataramanreported that the presence of antioxidant potentials in extractof T cordifolia was a potent healer in ameliorating diabeteslike tissue damage in vivo [48] It is perfectly consistentwith the report that T cordifolia has a significant (119875 lt005) effect in ameliorating the specific parameters towardnormal in diabetic animals and it has a level of efficacythat is considerably good compared to standard drug insulin[49] These experimental results further enrich previousunderstanding of the antidiabetic activity of genus Tinosporaand provide scientific data of therapeutic efficacy againstdiabetes mellitus

33 Immunostimulatory Activity Several Tinospora specieshave effects on humoral immunity cellular immunity andnonspecific immunity Polysaccharide a kind of naturalmacromolecule has widespread occurrence in biologicalbodies and has many kinds of biological activities whichplays an important role in regulating immune system [50]Polysaccharides in Tinospora represent a structurally diverseclass of macromolecules and this structural variability canprofoundly affect their cell-type specificity and their bio-logical activity in B cells Previous studies documented that

Evidence-Based Complementary and Alternative Medicine 5

phytogenic polysaccharides could regulate animalsrsquo immunesystem by combining tomembrane receptors of immune cellsand initiating the special signaling pathways This includesstimulating the secretion or proliferation of macrophagesTB lymphocytes and natural killer (NK) cells modulatingthe release of cytokines promoting the production of anti-bodies and activating the complement system [51] (14)-120572-D-Glucan (120572-DG) is a novel immune stimulatory drug fromT cordifolia It exhibited macrophages activating abilitiesthrough TLR6 signaling and NF-120581B activation mechanismfollowed by the production of cytokines and chemokinesIt can also differentially modulate cytokine production inthe spleen and lung on endotoxaemic juvenile rats In thelung 120572-DG treatment reduced anti-inflammatory cytokineconcentrations of IL-1120573 by 30 IL-6 by 43 IFN-120574 by46 and IL-10 by 31 compared to endotoxaemia Inthe spleen 120572-DG treatment decreased the ratio of IL-1120573to IL-10 by 55 [52ndash54] Further data showed that 120572-DG led to significant tachycardia without causing hypoten-sion Accompanied by significant reduction in the bloodhemoglobin and hematocrit concentrations the effect did notchange respiratory variable andor plasma concentration ofinflammatory cytokines in anaesthetized rats [55] G1-4A anarabinogalactan polysaccharide from T cordifolia is a well-characterized immunomodulatory in both in vitro and in vivosystems Administration (125mgkg body weight) of G1-4Ato mice led to splenomegaly and an increase in the numbersof T cells B cells and macrophages This increase in spleencellularity was due to in vivo proliferation of lymphocytesand upregulation of antiapoptotic genes G1-4A inducedproliferation of B cells was completely inhibited by PI3Kinhibitor Ly294002 mTOR inhibitor rapamycin and NF-120581Binhibitor plumbagin Meanwhile Akt ERK and JNK wereactivated by G1-4A which finally resulted in the activationof IKK degradation of I120581B-120572 and translocation of NF-120581Bto the nucleus [56ndash58] In the humoral and cell-mediatedimmune response T cordifolia preparation enhanced meanhemagglutination antibody titre and reactive oxygen levelagainst various pathogens [59ndash61] Polar fractions of Tcordifolia stem at a dose of 40mgkg body weight promotedthe nonspecific host and defence of the immune systemdirectly acted on peritonealmacrophages [13] T crispa crudeextract significantly stimulated RAW 2647 cell viability (119875 le005) and intracellular INF-120574 IL-6 and IL-8 expressionsStudy of LC-MS showed that the immunomodulatory activecompounds are cordioside quercetin eicosenoic acid andboldine [62] Other reports indicated that it is the syn-ergistic effect of immunomodulatory active compounds ingenus Tinospora that contributed to the immunomodulatoryactivity [61 63] As mentioned above polysaccharides ingenus Tinospora play a key role in the immunostimulatoryactivityThe characteristics of polysaccharides which includebackbone structure branching degree molecular weight andthree spiral structures affected the activity of immunityBy activating the inherent and acquired immune systemto produce antitumor immunity the immunomodulatoryactivity could also contribute to the tumor immunotherapy[64]

34 Antitumor Activity Feature chemical components ofTinospora clerodane diterpenes showed apparent cytotoxicactivity against tumor cells [65] Nowadays the antitumoreffect of the Tinospora species has been widely studied in vivoand in vitro The mechanisms of the antitumor activity ofTinospora species aremainly concentrated on the cytotoxicityand cell apoptosis induced Epoxy clerodane diterpenes wereevaluated for the activity against diethylnitrosamine-inducedhepatocyte carcinoma the results concluded that they kickin blocking carcinogen metabolic activation and enhancingcarcinogen detoxification [66 67] Aqueous ethanolic ingre-dients of T cordifolia reduced cell proliferation in dose-dependent manner and induced differentiation in C

6glioma

cells The cell proliferation inhibition was in part mediatedthrough accumulation in S phase and G2M arrest withconcomitant suppression of p21 expression and inhibition ofcyclin-dependent kinase activity [68] Treatment of hexaneextract fraction of T cordifolia on Ehrlich ascites tumorbearing animals resulted in growth inhibition and inductionof apoptosis in a dose-dependent manner in vivo The mech-anism of action was caspase-3 dependent which caused anuclear localization of apoptosis meanwhile the formation ofapoptotic bodies nuclear condensation typical DNA ladderand decreased cell number and ascites volume [7] More andPai observed that treatment with T cordifolia and LPS ofmacrophage cell line J774A1 followed the enhanced NADH-oxidase NADPH-oxidase and myeloperoxidase productionas compared to medium alone [69] According to recentstudies alkaloids chemical constituents from plants havethe characteristics of better antitumor activity high effectgood tolerance and slight side effect [70] Alkaloid especiallypalmatine from T cordifolia significantly decreased tumorsize number and the activity of serum enzyme in DMBAinduced skin cancer mice The alkaloid could also contributeto the reduction of glutathione (GSH) superoxide dismutase(SOD) and catalase however it increased DNA damage [71]The activation of macrophages is another pathway for antitu-mor activity (14)-120572-D-Glucan andG1-4A are immunologicalactive polysaccharides from T cordifolia Treatment withG1-4A on a murine lymphoma model increased T cellallostimulatory activity and secretion of IL-12 and TNF120572 bybone marrow derived dendritic cells leading to the lysis oftarget tumor cells in vitro Polysaccharides can also activatemacrophages NK cells APDs and T and B lymphocytesto enhance antitumor immunity concerned with secretionof cytokines activation of the complement system induc-tion of apoptosis of tumor cells and intracellular signaltransduction so as to achieve the tumor inhibitory effectby regulations of the immune system [56 72] Sonaimuthuet al identified taxol producing endophytic fungus F cul-morum SVJM072 from medicinal plant of T cordifoliaFurther research showed that the fungal taxol had strongactivity against human cancer cell lines by MTT assay andM tuberculosis H37Rv by Radiometric Bactec 460 assaywhich could serve as an excellent alternative source anda genetically engineered species for anticancer compounds[73]

6 Evidence-Based Complementary and Alternative Medicine

35 Anti-Inflammatory and Antimicrobial Activity Inflam-mation is a pathologic condition that includes a wide rangeof diseases such as rheumatic and immune-mediated con-ditions diabetes and cardiovascular accident If the processof inflammatory response cannot end normally when celldebris and pathogens were cleared the biological defenceresponse will become causative factor Medicinal plants andtheir secondary metabolites are progressively used in thetreatment of diseases as a complementary medicine [7475] Palmatine and jatrorrhizine mainly separated fromtubers of T capillipes and T cordifolia have widely beenapplied in clinic owing to their comparatively broad spectruminhibitory activity With the EC

50values ranged from 00348

to 08356 gL and 00240 to 08649 gL respectively palma-tine and jatrorrhizine exhibited inhibition against many plantpathogens The two alkaloids vary only in the substituents ofposition 3 of A ring in terms of the chemical structure Theeffectiveness of protoberberine was related to the ammoniumN linked at position 7 of aromatic ring in the chemicalstructure and the inhibitory activity of protoberberine alka-loids altered by the different substituents in A and D rings[76] The ethanol extract of T smilacina showed inhibitoryactivities on COX-1 COX-2 5-LO and PA

2with the IC

50

values of 635 812 921 and 305 120583gmL respectively [9]Considerable decrease in the levels of iNOS COX-2 andICAM-1 resulted in the reduced release of proinflammatorymediators like TNF-120572 IL-4 NO and IgE [10] An insightinto the antimicrobial activity of the ethanolic extracts of Tcordifolia indicated that the secondary metabolites exhibitedhigh inhibitory activity against clinically isolated S aureusand K pneumoniae [11] It is noteworthy that inductionof embryogenic callus of T cordifolia with the presence ofadditional compoundswas able to inhibit bothGram-positiveand Gram-negative organisms [77] All in all inflammationis a complex and multifaceted problem so the treatmentof inflammation is not a one-dimensional remedy Theanti-inflammation of herbal medicine belonging to genusTinospora has a favorable applied perspective with the helpof modification in structure it may assist in reaching amultidimensional therapeutic approach to inflammation inthe future [78]

36 Antiosteoporosis Activity During recent years researchesin traditional Chinese medicine for the treatment of osteo-porosis are increasing especially in the research and ther-apeutic application using compound medicine and exter-nal medicine and some progress has been made [79] Tcapillipes and T cordifolia were reported to induce alkalinephosphatase activity in mesenchymal stem cells based onecdysone compounds At the dosage of 25120583gmL ethanolicextracts of T cordifolia stimulated the growth of osteoblastsincreased the differentiation of cells into osteoblastic lineageand increased the mineralization of bone-like matrix onboth the osteoblast model systems Previously Gao et alnoted that the stem extracts of T cordifolia in ovariec-tomized rats significantly prevented the bone loss in ratsinduced by ovariectomy without causing proliferative effectsin uterus and mammary gland [80 81] In addition thepresence of high concentration of calcium in T cordifolia

made it a natural cure for osteoporosis [12] Moreover singleor synergistic formulations of T cordifolia with Zingiberofficinale have been used in ancient India medicinal systemto treat rheumatoid arthritis [34] However the morbidityof osteoporosis has been linked to several factors such asage gender and races In order to get a good outcomeof osteoporosis treatment both surgical management andpharmacological treatment are necessary

37 OtherTherapeutic Activities What ismoreTinospora hasbeen investigated to exert other pharmacological activitiesCordifolioside Amainly isolated in T cordifolia has a poten-tial in vivo radioprotective effect and in vitro cytoprotectiveactivity [82] The impressive radioprotective efficacy may berelated to the attenuation of radiation induced decrease ofadherence and spreading increase of IL-1120573 and GM-CSFlevels and reduction of apoptosis [83]The radiosensitizationby T cordifoliamay be also due to depletion of GSH andGSTaccompanied by elevated levels of LPx and DNA damage oftumor cells [84]

Ethanolic extract of T sinensis exhibited an appreciableactivity against promastigotes (IC

50376 plusmn 62 120583gmL) and

intracellular amastigotes (IC50298 plusmn 34 120583gmL) In ham-

sters it resulted in 762 plusmn 92 inhibition at 500mgkgday times5 oral dose levels [19ndash24] T cordifolia (100mgkg bwtfor 15 days daily) used in combination with cisplatin in Ldonovani infected BALBc mice selectively induced Th1 typeof immune response It was concluded by the enhanced levelsof IFN-c and IL-2 with moderate decline of Th2 specificcytokines IL-4 and IL-10 [85]

The least polar alkaloid from T crispa columbamineshowed strong acetyl-cholinesterase inhibitory activitywith IC

504810 120583molL The structure-activity relationships

derived from these results suggested that the quaternarynitrogen in the skeleton has some effect but that a high degreeof methoxylation is more important for acetylcholinesteraseinhibition [86]

T cordifolia ethanol extract exhibited significant neuro-protection by increasing the dopamine levels (196 plusmn 020and 245 plusmn 040 ngmg of protein) and complex I activity(7714plusmn 089 and 7850plusmn 096 nmolminmg of protein) at 200and 400mgkg respectively [87] Combination of ethanolicextracts of T cordifolia B monnieri and E alsinoides inequal proportion provided synergistic nootropic effect onscopolamine induced amnesia in rats [88]

4 Chemical Constituents

The chemical constituents of Tinospora have long been thepursued objectives of the researchers and multiple classesof chemical constituents have been isolated and reportedWithin these compounds diterpenoids are the most domi-nant constituent found in the currently studied species in thisgenus Up to now 223 compounds have been isolated fromgenus Tinospora including terpenoids alkaloids steroidsC6-C3derivatives and polysaccharides as well as other

components The compounds list and their structures areshown in Table 2 and Figure 1

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 5

phytogenic polysaccharides could regulate animalsrsquo immunesystem by combining tomembrane receptors of immune cellsand initiating the special signaling pathways This includesstimulating the secretion or proliferation of macrophagesTB lymphocytes and natural killer (NK) cells modulatingthe release of cytokines promoting the production of anti-bodies and activating the complement system [51] (14)-120572-D-Glucan (120572-DG) is a novel immune stimulatory drug fromT cordifolia It exhibited macrophages activating abilitiesthrough TLR6 signaling and NF-120581B activation mechanismfollowed by the production of cytokines and chemokinesIt can also differentially modulate cytokine production inthe spleen and lung on endotoxaemic juvenile rats In thelung 120572-DG treatment reduced anti-inflammatory cytokineconcentrations of IL-1120573 by 30 IL-6 by 43 IFN-120574 by46 and IL-10 by 31 compared to endotoxaemia Inthe spleen 120572-DG treatment decreased the ratio of IL-1120573to IL-10 by 55 [52ndash54] Further data showed that 120572-DG led to significant tachycardia without causing hypoten-sion Accompanied by significant reduction in the bloodhemoglobin and hematocrit concentrations the effect did notchange respiratory variable andor plasma concentration ofinflammatory cytokines in anaesthetized rats [55] G1-4A anarabinogalactan polysaccharide from T cordifolia is a well-characterized immunomodulatory in both in vitro and in vivosystems Administration (125mgkg body weight) of G1-4Ato mice led to splenomegaly and an increase in the numbersof T cells B cells and macrophages This increase in spleencellularity was due to in vivo proliferation of lymphocytesand upregulation of antiapoptotic genes G1-4A inducedproliferation of B cells was completely inhibited by PI3Kinhibitor Ly294002 mTOR inhibitor rapamycin and NF-120581Binhibitor plumbagin Meanwhile Akt ERK and JNK wereactivated by G1-4A which finally resulted in the activationof IKK degradation of I120581B-120572 and translocation of NF-120581Bto the nucleus [56ndash58] In the humoral and cell-mediatedimmune response T cordifolia preparation enhanced meanhemagglutination antibody titre and reactive oxygen levelagainst various pathogens [59ndash61] Polar fractions of Tcordifolia stem at a dose of 40mgkg body weight promotedthe nonspecific host and defence of the immune systemdirectly acted on peritonealmacrophages [13] T crispa crudeextract significantly stimulated RAW 2647 cell viability (119875 le005) and intracellular INF-120574 IL-6 and IL-8 expressionsStudy of LC-MS showed that the immunomodulatory activecompounds are cordioside quercetin eicosenoic acid andboldine [62] Other reports indicated that it is the syn-ergistic effect of immunomodulatory active compounds ingenus Tinospora that contributed to the immunomodulatoryactivity [61 63] As mentioned above polysaccharides ingenus Tinospora play a key role in the immunostimulatoryactivityThe characteristics of polysaccharides which includebackbone structure branching degree molecular weight andthree spiral structures affected the activity of immunityBy activating the inherent and acquired immune systemto produce antitumor immunity the immunomodulatoryactivity could also contribute to the tumor immunotherapy[64]

34 Antitumor Activity Feature chemical components ofTinospora clerodane diterpenes showed apparent cytotoxicactivity against tumor cells [65] Nowadays the antitumoreffect of the Tinospora species has been widely studied in vivoand in vitro The mechanisms of the antitumor activity ofTinospora species aremainly concentrated on the cytotoxicityand cell apoptosis induced Epoxy clerodane diterpenes wereevaluated for the activity against diethylnitrosamine-inducedhepatocyte carcinoma the results concluded that they kickin blocking carcinogen metabolic activation and enhancingcarcinogen detoxification [66 67] Aqueous ethanolic ingre-dients of T cordifolia reduced cell proliferation in dose-dependent manner and induced differentiation in C

6glioma

cells The cell proliferation inhibition was in part mediatedthrough accumulation in S phase and G2M arrest withconcomitant suppression of p21 expression and inhibition ofcyclin-dependent kinase activity [68] Treatment of hexaneextract fraction of T cordifolia on Ehrlich ascites tumorbearing animals resulted in growth inhibition and inductionof apoptosis in a dose-dependent manner in vivo The mech-anism of action was caspase-3 dependent which caused anuclear localization of apoptosis meanwhile the formation ofapoptotic bodies nuclear condensation typical DNA ladderand decreased cell number and ascites volume [7] More andPai observed that treatment with T cordifolia and LPS ofmacrophage cell line J774A1 followed the enhanced NADH-oxidase NADPH-oxidase and myeloperoxidase productionas compared to medium alone [69] According to recentstudies alkaloids chemical constituents from plants havethe characteristics of better antitumor activity high effectgood tolerance and slight side effect [70] Alkaloid especiallypalmatine from T cordifolia significantly decreased tumorsize number and the activity of serum enzyme in DMBAinduced skin cancer mice The alkaloid could also contributeto the reduction of glutathione (GSH) superoxide dismutase(SOD) and catalase however it increased DNA damage [71]The activation of macrophages is another pathway for antitu-mor activity (14)-120572-D-Glucan andG1-4A are immunologicalactive polysaccharides from T cordifolia Treatment withG1-4A on a murine lymphoma model increased T cellallostimulatory activity and secretion of IL-12 and TNF120572 bybone marrow derived dendritic cells leading to the lysis oftarget tumor cells in vitro Polysaccharides can also activatemacrophages NK cells APDs and T and B lymphocytesto enhance antitumor immunity concerned with secretionof cytokines activation of the complement system induc-tion of apoptosis of tumor cells and intracellular signaltransduction so as to achieve the tumor inhibitory effectby regulations of the immune system [56 72] Sonaimuthuet al identified taxol producing endophytic fungus F cul-morum SVJM072 from medicinal plant of T cordifoliaFurther research showed that the fungal taxol had strongactivity against human cancer cell lines by MTT assay andM tuberculosis H37Rv by Radiometric Bactec 460 assaywhich could serve as an excellent alternative source anda genetically engineered species for anticancer compounds[73]

6 Evidence-Based Complementary and Alternative Medicine

35 Anti-Inflammatory and Antimicrobial Activity Inflam-mation is a pathologic condition that includes a wide rangeof diseases such as rheumatic and immune-mediated con-ditions diabetes and cardiovascular accident If the processof inflammatory response cannot end normally when celldebris and pathogens were cleared the biological defenceresponse will become causative factor Medicinal plants andtheir secondary metabolites are progressively used in thetreatment of diseases as a complementary medicine [7475] Palmatine and jatrorrhizine mainly separated fromtubers of T capillipes and T cordifolia have widely beenapplied in clinic owing to their comparatively broad spectruminhibitory activity With the EC

50values ranged from 00348

to 08356 gL and 00240 to 08649 gL respectively palma-tine and jatrorrhizine exhibited inhibition against many plantpathogens The two alkaloids vary only in the substituents ofposition 3 of A ring in terms of the chemical structure Theeffectiveness of protoberberine was related to the ammoniumN linked at position 7 of aromatic ring in the chemicalstructure and the inhibitory activity of protoberberine alka-loids altered by the different substituents in A and D rings[76] The ethanol extract of T smilacina showed inhibitoryactivities on COX-1 COX-2 5-LO and PA

2with the IC

50

values of 635 812 921 and 305 120583gmL respectively [9]Considerable decrease in the levels of iNOS COX-2 andICAM-1 resulted in the reduced release of proinflammatorymediators like TNF-120572 IL-4 NO and IgE [10] An insightinto the antimicrobial activity of the ethanolic extracts of Tcordifolia indicated that the secondary metabolites exhibitedhigh inhibitory activity against clinically isolated S aureusand K pneumoniae [11] It is noteworthy that inductionof embryogenic callus of T cordifolia with the presence ofadditional compoundswas able to inhibit bothGram-positiveand Gram-negative organisms [77] All in all inflammationis a complex and multifaceted problem so the treatmentof inflammation is not a one-dimensional remedy Theanti-inflammation of herbal medicine belonging to genusTinospora has a favorable applied perspective with the helpof modification in structure it may assist in reaching amultidimensional therapeutic approach to inflammation inthe future [78]

36 Antiosteoporosis Activity During recent years researchesin traditional Chinese medicine for the treatment of osteo-porosis are increasing especially in the research and ther-apeutic application using compound medicine and exter-nal medicine and some progress has been made [79] Tcapillipes and T cordifolia were reported to induce alkalinephosphatase activity in mesenchymal stem cells based onecdysone compounds At the dosage of 25120583gmL ethanolicextracts of T cordifolia stimulated the growth of osteoblastsincreased the differentiation of cells into osteoblastic lineageand increased the mineralization of bone-like matrix onboth the osteoblast model systems Previously Gao et alnoted that the stem extracts of T cordifolia in ovariec-tomized rats significantly prevented the bone loss in ratsinduced by ovariectomy without causing proliferative effectsin uterus and mammary gland [80 81] In addition thepresence of high concentration of calcium in T cordifolia

made it a natural cure for osteoporosis [12] Moreover singleor synergistic formulations of T cordifolia with Zingiberofficinale have been used in ancient India medicinal systemto treat rheumatoid arthritis [34] However the morbidityof osteoporosis has been linked to several factors such asage gender and races In order to get a good outcomeof osteoporosis treatment both surgical management andpharmacological treatment are necessary

37 OtherTherapeutic Activities What ismoreTinospora hasbeen investigated to exert other pharmacological activitiesCordifolioside Amainly isolated in T cordifolia has a poten-tial in vivo radioprotective effect and in vitro cytoprotectiveactivity [82] The impressive radioprotective efficacy may berelated to the attenuation of radiation induced decrease ofadherence and spreading increase of IL-1120573 and GM-CSFlevels and reduction of apoptosis [83]The radiosensitizationby T cordifoliamay be also due to depletion of GSH andGSTaccompanied by elevated levels of LPx and DNA damage oftumor cells [84]

Ethanolic extract of T sinensis exhibited an appreciableactivity against promastigotes (IC

50376 plusmn 62 120583gmL) and

intracellular amastigotes (IC50298 plusmn 34 120583gmL) In ham-

sters it resulted in 762 plusmn 92 inhibition at 500mgkgday times5 oral dose levels [19ndash24] T cordifolia (100mgkg bwtfor 15 days daily) used in combination with cisplatin in Ldonovani infected BALBc mice selectively induced Th1 typeof immune response It was concluded by the enhanced levelsof IFN-c and IL-2 with moderate decline of Th2 specificcytokines IL-4 and IL-10 [85]

The least polar alkaloid from T crispa columbamineshowed strong acetyl-cholinesterase inhibitory activitywith IC

504810 120583molL The structure-activity relationships

derived from these results suggested that the quaternarynitrogen in the skeleton has some effect but that a high degreeof methoxylation is more important for acetylcholinesteraseinhibition [86]

T cordifolia ethanol extract exhibited significant neuro-protection by increasing the dopamine levels (196 plusmn 020and 245 plusmn 040 ngmg of protein) and complex I activity(7714plusmn 089 and 7850plusmn 096 nmolminmg of protein) at 200and 400mgkg respectively [87] Combination of ethanolicextracts of T cordifolia B monnieri and E alsinoides inequal proportion provided synergistic nootropic effect onscopolamine induced amnesia in rats [88]

4 Chemical Constituents

The chemical constituents of Tinospora have long been thepursued objectives of the researchers and multiple classesof chemical constituents have been isolated and reportedWithin these compounds diterpenoids are the most domi-nant constituent found in the currently studied species in thisgenus Up to now 223 compounds have been isolated fromgenus Tinospora including terpenoids alkaloids steroidsC6-C3derivatives and polysaccharides as well as other

components The compounds list and their structures areshown in Table 2 and Figure 1

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Behavioural Neurology

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Disease Markers

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OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Research and TreatmentAIDS

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

6 Evidence-Based Complementary and Alternative Medicine

35 Anti-Inflammatory and Antimicrobial Activity Inflam-mation is a pathologic condition that includes a wide rangeof diseases such as rheumatic and immune-mediated con-ditions diabetes and cardiovascular accident If the processof inflammatory response cannot end normally when celldebris and pathogens were cleared the biological defenceresponse will become causative factor Medicinal plants andtheir secondary metabolites are progressively used in thetreatment of diseases as a complementary medicine [7475] Palmatine and jatrorrhizine mainly separated fromtubers of T capillipes and T cordifolia have widely beenapplied in clinic owing to their comparatively broad spectruminhibitory activity With the EC

50values ranged from 00348

to 08356 gL and 00240 to 08649 gL respectively palma-tine and jatrorrhizine exhibited inhibition against many plantpathogens The two alkaloids vary only in the substituents ofposition 3 of A ring in terms of the chemical structure Theeffectiveness of protoberberine was related to the ammoniumN linked at position 7 of aromatic ring in the chemicalstructure and the inhibitory activity of protoberberine alka-loids altered by the different substituents in A and D rings[76] The ethanol extract of T smilacina showed inhibitoryactivities on COX-1 COX-2 5-LO and PA

2with the IC

50

values of 635 812 921 and 305 120583gmL respectively [9]Considerable decrease in the levels of iNOS COX-2 andICAM-1 resulted in the reduced release of proinflammatorymediators like TNF-120572 IL-4 NO and IgE [10] An insightinto the antimicrobial activity of the ethanolic extracts of Tcordifolia indicated that the secondary metabolites exhibitedhigh inhibitory activity against clinically isolated S aureusand K pneumoniae [11] It is noteworthy that inductionof embryogenic callus of T cordifolia with the presence ofadditional compoundswas able to inhibit bothGram-positiveand Gram-negative organisms [77] All in all inflammationis a complex and multifaceted problem so the treatmentof inflammation is not a one-dimensional remedy Theanti-inflammation of herbal medicine belonging to genusTinospora has a favorable applied perspective with the helpof modification in structure it may assist in reaching amultidimensional therapeutic approach to inflammation inthe future [78]

36 Antiosteoporosis Activity During recent years researchesin traditional Chinese medicine for the treatment of osteo-porosis are increasing especially in the research and ther-apeutic application using compound medicine and exter-nal medicine and some progress has been made [79] Tcapillipes and T cordifolia were reported to induce alkalinephosphatase activity in mesenchymal stem cells based onecdysone compounds At the dosage of 25120583gmL ethanolicextracts of T cordifolia stimulated the growth of osteoblastsincreased the differentiation of cells into osteoblastic lineageand increased the mineralization of bone-like matrix onboth the osteoblast model systems Previously Gao et alnoted that the stem extracts of T cordifolia in ovariec-tomized rats significantly prevented the bone loss in ratsinduced by ovariectomy without causing proliferative effectsin uterus and mammary gland [80 81] In addition thepresence of high concentration of calcium in T cordifolia

made it a natural cure for osteoporosis [12] Moreover singleor synergistic formulations of T cordifolia with Zingiberofficinale have been used in ancient India medicinal systemto treat rheumatoid arthritis [34] However the morbidityof osteoporosis has been linked to several factors such asage gender and races In order to get a good outcomeof osteoporosis treatment both surgical management andpharmacological treatment are necessary

37 OtherTherapeutic Activities What ismoreTinospora hasbeen investigated to exert other pharmacological activitiesCordifolioside Amainly isolated in T cordifolia has a poten-tial in vivo radioprotective effect and in vitro cytoprotectiveactivity [82] The impressive radioprotective efficacy may berelated to the attenuation of radiation induced decrease ofadherence and spreading increase of IL-1120573 and GM-CSFlevels and reduction of apoptosis [83]The radiosensitizationby T cordifoliamay be also due to depletion of GSH andGSTaccompanied by elevated levels of LPx and DNA damage oftumor cells [84]

Ethanolic extract of T sinensis exhibited an appreciableactivity against promastigotes (IC

50376 plusmn 62 120583gmL) and

intracellular amastigotes (IC50298 plusmn 34 120583gmL) In ham-

sters it resulted in 762 plusmn 92 inhibition at 500mgkgday times5 oral dose levels [19ndash24] T cordifolia (100mgkg bwtfor 15 days daily) used in combination with cisplatin in Ldonovani infected BALBc mice selectively induced Th1 typeof immune response It was concluded by the enhanced levelsof IFN-c and IL-2 with moderate decline of Th2 specificcytokines IL-4 and IL-10 [85]

The least polar alkaloid from T crispa columbamineshowed strong acetyl-cholinesterase inhibitory activitywith IC

504810 120583molL The structure-activity relationships

derived from these results suggested that the quaternarynitrogen in the skeleton has some effect but that a high degreeof methoxylation is more important for acetylcholinesteraseinhibition [86]

T cordifolia ethanol extract exhibited significant neuro-protection by increasing the dopamine levels (196 plusmn 020and 245 plusmn 040 ngmg of protein) and complex I activity(7714plusmn 089 and 7850plusmn 096 nmolminmg of protein) at 200and 400mgkg respectively [87] Combination of ethanolicextracts of T cordifolia B monnieri and E alsinoides inequal proportion provided synergistic nootropic effect onscopolamine induced amnesia in rats [88]

4 Chemical Constituents

The chemical constituents of Tinospora have long been thepursued objectives of the researchers and multiple classesof chemical constituents have been isolated and reportedWithin these compounds diterpenoids are the most domi-nant constituent found in the currently studied species in thisgenus Up to now 223 compounds have been isolated fromgenus Tinospora including terpenoids alkaloids steroidsC6-C3derivatives and polysaccharides as well as other

components The compounds list and their structures areshown in Table 2 and Figure 1

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

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Computational and Mathematical Methods in Medicine

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 7

Table 2 The compound list of genus Tinospora

Number Compounds Species (part of plant) ReferencesTerpenoids

1 Tinocapillins C T capillipes (R) [123]2 Tinocallone A T capillipes (R) [107]3 Tinocallone B T capillipes (R) [107]4 Tinocordin T cordifolia [124]5 Tinocapillins A T capillipes (R) [123]6 Fibaruretin H T sagittata (R) [125]7 Tinocapillins B T capillipes (R) [123]8 Fibaruretin G T sagittata (R) [125]9 Sagitone T sagittata var yunnanensis (R) [93]10 Tinosponone T cordifolia (S) [113]11 Tinosporaside T cordifolia (S) [100 113]12 Tinosporaside tetraacetate T cordifolia (S) [113]13 Amritoside D T cordifolia (S) [109]14 Tinocordioside T cordifolia (S) [109]15 Tinocordioside tetraacetate T cordifolia (S) [109]16 Boropetol B T crispa (S) [126]17 Tinocrisposide T crispa (S) [127]18 Boropetoside F T tuberculata (S) [128]

19(2R5R6S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-

tetraen-1712-olid-18-oic acid methylester

T crispa [114]

20(5R6S9S10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-3713(16)14-tetraen-

1712-olid-18-oic acid methylester

T crispa [91]

21(5R6R8S9R10S12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-

olid-18-oic acid methylester

T crispa [91]

22

(2R5R6R8S9S10S12S)-1516-Epoxy-2-hydroxy-6-O-120573-D-glucopyranosyl-(1rarr6)-120572-D-

xylopyranosyl-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

23(2R5R6R8R9S10S12S)-1516-Epoxy-2-hydroxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-

trien-1712-olid-18-oic acid methylester

T crispa [91]

24(5R6R8S9R10R12S)-1516-Epoxy-2-oxo-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-

1712-olid-18-oic acid methylester

T crispa [91]

25 Borapetoside B T crispa [38 91]26 Borapetoside C T crispa [38 91]27 Tinophylloloside T sagittata var yunnanensis (R) [92]

28 Epitinophylloloside T sagittata var yunnanensis (R)T capillipes (R) [107]

29 Tinoscorside C T cordifolia [94]30 Borapetoside F T cordifolia [94]31 Borapetoside B T cordifolia [94]

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

8 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References32 Tinocrispol A T crispa (S) [129]33 Amritoside C T cordifolia (S) [109]34 2-O-Lactoylborapetoside B T crispa (S) [129]35 61015840-O-Lactoylborapetoside B T crispa (S) [129]36 Borapetoside H T tuberculata (S) [95]37 Octa-O-acetylborapetoside H T tuberculata (S) [95]38 Borapetoside H T crispa (S) [96]39 Tinospinoside C T sagittata var yunnanensis (R) [97]40 Tinospinoside A T sagittata (Oliv)Gagnep(R) [98]41 Tinospinoside B T sagittata (Oliv)Gagnep(R) [98]42 Rumphioside A T rumphii (S) [117]43 Rumphioside B T rumphii (S) [117]44 Rumphioside C T rumphii (S) [117]45 Rumphioside D T rumphii (S) [117]46 Furanoid diterpene glycoside T cordifolia (S) [130]47 Cordioside T cordifolia (S) [99]48 Cordioside tetraacetate T cordifolia (S) [99]49 Cordifoliside D T cordifolia (S) [100]50 Cordifoliside E T cordifolia (S) [100]51 Boropetoside G T tuberculata (S) [128]52 Malabarolide T malabarica (S) [131]53 Tinosposinenside A T sinensis (S) [101]54 Tinosposinenside B T sinensis (S) [101]55 Tinosposinenside C T sinensis (S) [101]56 1-Deacetyltinosposide A T sinensis (S) [103]57 Tinosineside A T sinensis (S) [103 104]58 Tinosineside B T sinensis (S) [104]59 Penta-O-acetyl-tinosineside A T sinensis (S) [104]60 Hexa-O-acetyl-tinosineside A T sinensis (S) [104]

61(3R4R5R6S8R9S10S12S)-1516-Epoxy-34-epoxy-6-O-(120573-D-glucopyranosyl)-cleroda-313(16)14-trien-1712-olid-18-oic acid methyl

ester

T crispa [91]

62 Tinospinoside D T sagittata (R) [105 132]63 Tinosporide T cordifolia (S) [113]64 Furanolactone clerodane diterpene T cordifolia (S) [113]65 Furanolactone clerodane diterpene T cordifolia (S) [113]66 Tinosporicide T malabarica (S) [113]67 Jateorin T smilacina (S) [114]68 Palmatoside F T smilacina (S) [114]

69 (5R10R)-4R8R-Dihydroxy-2S3R1516-diepoxycleroda-13(16)1712S181S-dilactone T cordifolia (S) [110]

70 Menispermacide T malabarica (S) [127]71 Tinosporaside T cordifolia (S) [113]72 Ioa-hydroxy columbin T malabarica (S) [131]

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

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Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 9

Table 2 Continued

Number Compounds Species (part of plant) References73 Tinoside T capillipes (Rh) [107]74 Isocolumbin T capillipes (Rh) [107]

75 ColumbinT craveniana (R)

T sagittata var yunnanensis (R)T capillipes (R)

[92 93 106 107 132 133]

76 Palmatoside C T sagittata var yunnanensis (R)T capillipes (R) [93 107 115]

77 Fibleucin T sagittata var yunnanensis (R)T capillipes (R) [93]

78 IsocolumbinT capillipes (R)T sagittata (R)T craveniana (R)

[92 106 107 133]

79 Tinoside T sagittata (R)T capillipes (R) [106]

80 6-Hydroxy columbin T sagittata (R) [92]

81(1R4S5R8S9R10S12S)-1516-Epoxy-4-O-(120573-D-

glucopyranosyl)-cleroda-213(16)14-triene-17(12)18(1)-diolide

T crispa [91]

82 Tinospinoside E T sagittata var yunnanensis (R) [98]83 8-Hydroxy columbin T cordifolia [116 128]84 Tinospin E T sagittata (R) [105 112]85 Cordifolide B T cordifolia (S) [108]86 Cordifolide C T cordifolia (S) [108]87 Furanolactone diterpene T cordifolia (S) [113]88 Boropetol A T crispa (S) [134]89 Boropetoside A T crispa (S) [134]90 Cordifolide A T cordifolia (S) [108]91 Menispermacide T smilacina (S) [114]92 Borapetoside A T crispa [91]93 Tinosporaclerodanoid T cordifolia (S) [102]94 Tinotufolin A T tuberculata (L) [116 128]95 Tinotufolin B T tuberculata (L) [116 128]96 Amritoside B T cordifolia (S) [109]97 Tinotufolin C T crispa (S) [96]

98Methyl(11205724120572a512057261205738a120572)-5-2-(3-furan-3-ene-2-one)ethyl-12344a56788a-decahydro-12-

dihydroxy-1-naphthalenecarboxylateT rumphii (L) [115]

99 Tinotufolin F T crispa (S) [96]100 Tinotufolin E T crispa (S) [96]101 Sagittatayunnanoside B T sagittata var yunnanensis (R) [97]102 Sagittatayunnanoside A T sagittata var yunnanensis (R) [97]103 Sagittatayunnanoside C T sagittata var yunnanensis (R) [97]104 Sagittatayunnanoside D T sagittata var yunnanensis (R) [97]105 Amritoside A T cordifolia (S) [109]106 Tinosagittone A T sagittata (R) [92]107 Tinosagittone B T sagittata (R) [92]108 Tinocapilactone A T capillipes [107]

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Disease Markers

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OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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PPAR Research

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Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

10 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References109 Tinocapilactone B T capillipes [107]110 Tinosporafuranol T cordifolia (S) [102]111 Tinosporaclerodanol T cordifolia (S) [102]112 Tinosporafurandiol T cordifolia (S) [100]

113(2a12057331205725a120573612057371205728a120572)-6-2-(3-Furanyl)ethyl-

2a3455a6788a8b-decahydro-2a3-dihydroxy-678b-trimethyl-2H-naphtho18-bcfuran-2-one

T rumphii (L) [104ndash115]

114 Boropetoside D T tuberculata (S) [116 128]115 Boropetoside E T tuberculata (S) [116 128]116 Tinotufolin D T crispa (S) [96]117 Borapetoside E T rumphii (S) [118]118 Rumphioside I T rumphii (S) [118]119 Rumphioside F T rumphii (S) [117]120 Rumphioside E T rumphii (S) [117]

121(2R7S8S)-8-[(2S)-2-(34-Dihydroxy-25-

dimethoxytetrahydro-3-furanyl)-2-hydroxyethyl]-28-dimethyl-10-oxo-11-

oxatricyclo[721027]dodec-3-ene-3-carboxylate

T crispa [91]

122 Borapetoside D T crispa [91]123 Baenzigeride B T baenzigeri (S) [120]124 Baenzigeroside B T baenzigeri (S) [120]125 Baenzigeride A T baezigeri (S) [120]126 Baenzigeroside A T baezigeri (S) [120]127 Cycloeuphordenol T malabarica (S) [113]128 Cycloeucalenol T crispa (S) [120]129 Cycloeucalenone T crispa (S) [120]130 Tinosinenside T sinensis (S) [101]131 11-Hydroxymustakone T capillipes [61 121 135]132 Tinocordiside T capillipes [61 121 135]

133 Tinocordifolioside T sinensis (S)T cordifolia (S) [103 122 136]

134 Tinocordifolin T cordifolia (S) [136]135 Tinocordifolioside tetraacetate T cordifolia (S) [136]

136 Angelicoidenol-2-O-120573-D-apiofuranosyl-(1rarr6)-120573-D-glucopyranoside T cordifolia [94]

Alkaloids137 Berberine T cordifolia (S) [113]

138 Palmatine T cordifolia (S)T malabarica (S) [127 137]

139 Jatrorrhizine T cordifolia (S)T capillipes (R) [137 138]

140 13-Hydroxycolumbamine T sagittata (R)T capillipes (R) [14 139]

141 13-Hydroxyjatrorrhizine T sagittata (R)T capillipes (R) [14 139]

142 Demethyleneberberine T sagittata (R)T capillipes (R) [14 139]

143 13-Hydroxypalmatine T sagittata (R)T capillipes (R) [14 139]

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Computational and Mathematical Methods in Medicine

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 11

Table 2 Continued

Number Compounds Species (part of plant) References

144 Columbamine T sagittata (R)T capillipes (R) [14 139]

145 JatrorrhizineT sagittata (R)T capillipes (R)T sinensis (S)

[14 106 139 140]

146 IsocolumbamineT hainanensis (S)T capillipes (R)T sagittata (R)

[106]

147 Stepharanine T sagittata (R)T capillipes (R) [14 139]

148 Dehydrodiscretamine T sagittata (R)T capillipes (R) [14 139]

149 Dehydrocorydalmine T sagittata (R)T capillipes (R) [14 106 139]

150 Palmaturbine T sinensisT craveniana (R) [14 133 139 140]

151 PalmatineT sinensis (S)T capillipes (R)T craveniana (R)

[103 106 133 140]

152 S-trans-N-Methyltetrahydrocolumbamine T hainanensis (S) [141]153 S-trans-Cyclanoline T hainanensis (S) [141]

154 3-Hydroxy-2911-trimethoxy-56-dihydro-isoquino32-a-isoquinolinylium T sinensis [140]

155 413-Dihydroxy-289-trimethoxydibenzo [ag]quinolizinium T crispa [86]

156 Berberine T smilacina (S) [92]

157 MagnoflorineT cordifolia (S)T malabarica (S)T capillipes (R)

[113 138]

158 Menisperine T capillipes (R)T cordifolia (S) [113 138]

159 N-Formyl anonaine T crispa (S)T malabarica (S) [113]

160 N-Formyl nornuciferine T crispa (S) [113]161 N-Acetyl nornuciferine T crispa (S) [38]162 N-Formylasimilobine-2-O-120573-D-glucopyranoside T crispa (S) [96]163 N-Formylannonain T capillipes [61 135]

164 Magnoflorine T sagittata (R)T capillipes (R) [14 106 139]

165 Menisperine T sagittata (R)T capillipes (R) [14 139]

166 Tembetarine T sagittata (R)T capillipes (R) [14 139]

167 Reticuline T sagittata (R)T capillipes (R) [14 139]

168 Tembetarine T cordifolia (S) [113]169 Higenamine T crispa [142]170 Adenine T crispa [142]171 Adenosine T crispa [143]172 Uridine T crispa [142]173 Salsolinol T crispa [142]

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

12 Evidence-Based Complementary and Alternative Medicine

Table 2 Continued

Number Compounds Species (part of plant) References174 (minus)-Litcubinine T crispa [142]175 Tyramine T crispa [142]176 N-trans-Feruloyl tyramine T tuberdata (S) [38]177 N-cis-Feruloyl tyramine T tuberculata (S) [36ndash38]178 N-trans-Feruloyl tyramine diacetate T cordifolia (S) [38 136]179 Kokusaginine T malabarica (S) [113]180 N-Methyl-2-pyrrolidone T capillipes [61 135]181 Choline T cordifolia (S) [137]

182 23-Dihydroxy-N-(2S3S4R)-134-trihydroxyicosan-2-yltetracosanamide T oblongifolia [144]

C6-C3-C6

183 Tinosporinone T malabarica (HW) [113]184 5-Alloxy-6741015840-trimethyl flavone T malabarica (HW) [113]185 Kaempferol T malabarica (S) [113]186 Astragalin T malabarica (S) [113]187 Quercitroside T malabarica (S) [113]188 (minus)-Epicatechin T cordifolia (S) [145]189 Ecoisolariciresinol T crispa [38]190 Secoisolariciresinol-91015840-O-120573-D-glucopyranoside T capillipes [38 94]191 Sagitiside A T sagittata var yunnanensis (R) [105 112]192 (+)-Lyoniresinol-2120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

193 (+)-51015840-Methoxyisolariciresinol-3120572-O-120573-D-glucopyranoside T sagittata var yunnanensis (R) [105 112]

1943(a4-dihydroxy-3-methoxybenzyl)-4-(4-

hydroxy-3-methoxybenzyl)tetrahydrofuran

T cordifolia (S) [113]

195 Lirioresino-120573-dimethyl ether T sinensis [140]196 Pinoresinol-di-O-glucoside T capillipes [94]197 (minus)-Pinoresinol-4-O-120573-D-glucopyranoside T sinensis (S) [103]198 81015840-Epitanegool T sinensis (S) [103]199 Syringin T crispa [142]200 Tinoscorside D T capillipes [94]201 Cordifolioside A T capillipes [38 61 135]202 Docosyl-34-dihydroxy-trans-cinnamate T oblongifolia [144]203 2-(40-Hydroxyphenyl)-ethyl lignocerate T oblongifolia [144]204 Tinotuberide T crispa (S) [113]205 Isoorientin 210158401015840-O-(E)-sinapate T crispa (L) [146]206 210158401015840-(E)-p-coumarate T crispa (L) [146]207 Cosmosiin 610158401015840-(E)-ferulate T crispa (L) [146]208 Cosmosiin 610158401015840-(E)-cinnamate T crispa (L) [146]

Steroids209

120573-Sitosterol T oblongifolia [144]210

120573-Sitosterol glycoside T oblongifolia [144]

211120573-Sitosterol

T cordifolia (S)T sinensis (S)

T craveniana (R)[102 140]

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 13

Table 2 Continued

Number Compounds Species (part of plant) References212 2-Deoxy crustecdysone T capillipes (R) [113]213 2-Deoxy-3-epicrustecdysone T capillipes (R) [113]

214 2-Deoxy-3-epicrustecdysone-3-O-D-glucopyranoside T capillipes (R) [113]

215 20120572-Hydroxy ecdysone T cordifolia (S) [113]216 20120573-Hydroxy-ecdysone-2-O-120573-glucopyranoside T craveniana (R) [147]

217 20120573-HydroxyecdysoneT sagittata (R)T capillipes (R)T craveniana (R)

[14 106 133 139]

218 2-Deoxy-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 106 139]

219 2-Deoxy-3-epi-20120573-hydroxyecdysone T sagittata (R)T capillipes (R) [14 139]

220 2-Deoxy-20120573-hydroxyecdysone-3-O-glucopyranoside

T sagittata (R)T capillipes (R) [14 106 139]

221 Polypodine B 2022-acetonide T cordifolia [94]222 Makisterone A T hainanensis (S) [148]223 24-Epi-makisterone A T hainanensis (S) [148]

41 Terpenoids

411 Diterpenes Diterpenoids with clerodane-type skeletonrepresent the second most prevalent chemical class of thegenus with over one hundred They are the characteristic-hot constituents containing 20-C atom forming a 66 bicyclicskeleton According to different stereochemistry of thedecalin ring junction this type of structure is grouped intoneo-clerodane ent-clerodane and nor-neo-clerodane Theskeleton of neo-clerodane and ent-clerodane-type diterpeneis the same with some differences in the configuration Thespatial locations of angular methyl group linked at C-5 C-8 and C-9 are differed Specifically it is C-5(S) C-8(R) andC-9(S) for neo-clerodane and C-5(R) C-8(S) and C-9(R)for ent-clerodaneNor-neo-clerodane is an oxidation productof neo-clerodane and one more five-membered unsaturatedlactone ring is added compared with neo-clerodane [89] Weprefer to divide the diterpenoids into another two majortypes A naphthalene ring fused to a lactone ring forms themain basic structure of the diterpenoids The C-9 positionoften has a six-membered side chain and usually forms afuran-ring moiety Lactone ring commonly exists in this typeof compounds Most of the lactone rings connect between C-8 and C-12 constituting the three six-membered rings withthe similar arrangement of phenanthrene Meanwhile thoseones without a lactone ring linked at C-8 and C-12 accountfor another small part of terpenoids Apart from what ismentioned above the few ones with isomerization in ring Cthen are in another group

(1) Diterpenes with Type 1 Skeleton Compounds with type1 skeleton are abundant in this genus Due to the decalincore motif Diels-Alder cycloaddition proved to be a valuabletool in their construction [90] However different syntheticroutes result in the different positions of double bond anddistinct substituents of the parallelized 66 bicyclic skeleton

These compounds are mostly reported from T cordifolia Tcrispa and T sagittata while other plant species possess afew Compounds 1ndash60 are typical clerodane-type diterpenescharacterized by the presence of one or more double bond ormethyl metabolites attached to the clerodane core [91ndash105]Compounds 61ndash86 have distinct connecting mode of lactonering linked at C-1C-18 with different spatial configurationsof substituent groups [91ndash93 106ndash112] Compounds 87ndash92as a tiny type caused more attention to be paid to the ethanethiolate group [101 108 113 114] Tinosporaclerodanoid (93)is a particular clerodane-type diterpene without a furan-ring at C-12 superseded by a butane terminated glycol neverisolated from a natural or synthetic source before Locationof the carbonyl group is determined to be at C-1 [102]

(2) Diterpenes with Type 2 Skeleton This is another type ofclerodane diterpene without the C-8C-12 linking lactonering yielding a variant genre of diterpenes featured by thedecalin ring junction of different stereochemistry In thesecompounds the C-8 position always contains a methyl ormethoxycarbonyl group which obstructs the formation ofthe lactone bridge between C-8 and C-12 see compounds 94to 112 They are mainly identified from T cordifolia T tuber-culate T sagittata var yunnanensis and T sagittata Thereis an ester bond connected between C-1 and C-4 (106ndash108)Onemore sugar glucose unit in sagittatayunnanoside C (103)indicates that itmay be the derivative of sagittatayunnanosideA (102) via the glycosylation of hydroxyl at C-18 [97 115]

(3) Diterpenes with Other Structures Compounds 113ndash116 arestructurally similar and the differences between the basicstructures are the oxidation degree of ring A The diversityamong their lactone ringmay be an influencing factor causingthese compounds to exhibit varying degrees of biologicalactivities against the same cancer cell line [96 115 116] Com-pounds 117ndash120 were isolated from the stem of T rumphii

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Oxidative Medicine and Cellular Longevity

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Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

14 Evidence-Based Complementary and Alternative Medicine

O

O

H

O(1)

H

OH

OH

OHH

OHO

O

O

(4)

O

O

O

H

O

(2)

O

O

O

H

O

(3)

H H

O

O

O

O

HO

H

H

(9)

O

O

O

H

O

(5)

O

O

O

H

O

(6)

H

O

O

O

OH

H

O

(7)

HO

O

O

H

O

(8)

HO

O

O

O

H

OR

H

HO

(10) R = H(11) R = 120573-D-Glc(12) R = tetra-O-acetyl-120573-D-Glc

O

O

H

O

OHH

OR

H

(13) R = 120573-D-Glc

O

O

O

H

OR

H

H

(14) R = 120573-D-Glc(15) R = tetra-O-acetyl-120573-D-Glc

O

H

O

H H

(16)

OH

HO

O

O

O

H

O

H

(17)

O

O

O

H

O

H

(18)

O

O

O

O

O

H

O

OOH

OHOH

HO

O

(19) OH(20) =O

O OO

OH

OHOH

HO

OOH

OHOH

HOH3CO H3CO H3CO H3CO

R1

R1

R2

R2

H

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 15

O

O

O

H

O

H

O

H

H

(21)

OOH

OHOH

HO

O

O

O

O

H

O

H

(22) H OH 120572-H(23) H OH 120573-H 120573-(120573-D-Glc)(24) =O 120572-H 120573-(120573-D-Glc)(25) H OH 120572-H 120572-(120573-D-Glc)(26) H H 120573-H 120573-(120573-D-Glc)

(27) R = 120572-H(28) R = 120573-H

O

O

O

H

R

O

GlcO

O

O

O

H

OH3C O

(29) H A OH(30) A H H(31) H A OH

A = -O-120573-D-Glc

O

O

OOH

H

O

HO

(32) (33) R = 120573-D-Glc

O

O

OH

OR

H

O

HO

O

O

O

H

O

O

OO HOOH

OH

(34) H 120572-H(35) Lactoyl 120572-H

O

O

OH

H

O

O

O

HO

HO

OO

(38)

O

O OHOHHO

OHHO

HO

OH

OH

O

O

H OH

O

(39)

OO

OHHOs-Bu

OH

O

R1

R1

R2

R2

H3CO H3COH3CO

R3

R3

R4

R4

120573-120573-D-Glc-(1rarr6)-120572-D-xylo

R1

R1

R2

R2

R3

R3

H3CO H3CO

R1

R3

H3CO CH2OR2

R1 R2 R3

H3COH3COOR2

H3CO

R1O

(36) R1 = R2 = 120573-D-Glcp

(37) R1 = R2 = 120573-D-Glcp(Ac)4

OHO-lactoyl

Figure 1 Continued

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

16 Evidence-Based Complementary and Alternative Medicine

O

GlcOH

H

H

O

O

(40)

O

O

GlcOH

H

OH

O

O

(41)

O

O

OR

O

O

HH

O

H

O

OHOHOH

HOO

(42) R = OH(43) R = OMe

O

O

O

HH

O

H

O

HO

HO

(44)

O

OHOHOH

HO

O

O

O

HH

O

H

OR

O

O

H

O

H H

(46)

OGlcO

O

O

O

H

O

H

(47) 120573-OH 120573-D-Glc(48) 120573-OH ltetra-O-acrtyl-120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(49) R = 120573-D-Glc

O

O

H

O

H

OH

H

RO

O

(50) R = 120573-D-Glc

O

O

H

O

H

(51)

OGlcO

O

H

O

H

(52)

OGlcOHH

OHOH

HO

O

O

O

OH

H

OO

OAc

(53)

OOH

HOHO

OH

O

O

OH

H

H

RO

O

(54) R = Ac(55) R = H

OAc

OOH

HOHO

OH

O

O

O

HHO

HO

H

OH

O

(56)

O

OH

OH

HOHO

O

O

O

H

H

OAc

OO

(57) H H H(58) Ac H H(59) Ac Ac H(60) Ac Ac Ac

H3CO H3CO H3COH3CO

OCH3

OCH3

H3CO

H3CO H3CO

H3CO

H3CO

H3CO

OCH3

(45) R =120573-D-Glc(Ac)4

R1

OR2

R1

H3CO

R2

CH2

R1 R3R2

OR3

R1O

OR2

R2OR2O

R2OH2C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 17

O

O

O

O

H

H

H

OGlcH

O

H

(61)

O

O

O

H

H

OGlc

OH

O

(62)

O

O

H

O

H H

OH

4O O O

(63)

O

H

O

H OH

OH

4O O O

(64)

O

O

H

O

H H

OH

4O O O

(65)

OH

O

O

H

O

OH H

OH

4O O

(66)

O

O

O

O

O

O

OOR

H

HO

H

(67) R = H(68) R = 120573-D-Glc

O

O

OHO

O OO

OH

(69)

O

H

O

H H

O O

(70)

HO

O

O

H

O

H H

GlcO

O O

(71)

O

O

H

O

OH H

OH

O O

(72)

O

O

H

O

H H

O O

(73)

OGlc

O

O

H

O

H

O O

(74)

OH

O

O

O

O

O

OOH

H

H

(75)

O

O

O

O

OOGlc

H

H

(76)

O

O

O

O

OOH

H

(77)

H3COH3COOC

H3C

CH3

Figure 1 Continued

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

18 Evidence-Based Complementary and Alternative Medicine

O

O

O

O

OOR

H

H

(78) R = H(79) R = Glc (80)

O

O

O

O

O

H

H

OH OH

O

O

O

O

O

O

H

H

(81)

OOH

OHOH

HO

O

O

H

OO

OO

(82)

O

OHHOHO

OH

OOH

OH

H

O

O

(83)

O

O

O

O

OO

O

H

H

(84)

O

OO

HOH

O

HH

O

O OO

OH

OH

HOHO

(85)

O

O

H

O

HH

O

O OO

OH

OH

HOHO

O

OH

(86)

O

H

O

H H

HO

(87)

HO

O

O

O

H

O

H H

(88)

HO

OO

O

O

O

OH

H

OO

HO

R

H

(92) R = 120573-D-Glc

O

OHOH

H

O

HO

HO

OH

(93)

O

H

O

H

(89)

H

HHOGlcO

OO

O

O

O

H

O

HH

OO

HOS

OO

HO

OH

HOHO

(90)

O

O

OH

H

H

OH

SS

OO

(91)

H3C

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 19

RH

O

OH

O

OH

OR

H

HO

O

(96) R = 120573-D-Glc

O

O

HO OH

H

(97)

O

O

H

HOHO

(98)

O

O

H

O

(99)

O

O

HO

H

(100)

O COOHH

OH

O

H

(101)

OO

OH

HOHO

O

OHHO HO

COOH

H

O

O

O

H

(102)

OHO OH

OH

O

OH

H

O

O

H

OO

(103)

OHOHO

OH

H HO

O

COOH

O

O

(104)

OHO

OHOH

O OHO

OHOH

OH

O

O

H

OR

H

H

OH

(105) R = 120573-D-Glc

O O

O

O

R

H

O

OH

(106) R = 120573-H(107) R = 120572-H

O O

OH

O

OH

O

O

(108)

OCH3 COOCH3

H3CO

CH2OH

HOH2C

H3CO OCH3

COR1

CH2OH

CH2OH

H3CO

CO2H

OCH3

OCH3

CO2H

H3CO

(94) R =120572-OH 120573-H R1 = OMe(95) R = H2 R1 = OH

Figure 1 Continued

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

20 Evidence-Based Complementary and Alternative Medicine

O O

OH

OOH

OO

(109)

OH

H O

R

(110) R = H(111) R = OH

OH

(112)

O

H

OO

HOHO

(113)

H

(115) R = 120573-D-Glc

H

OR

O

H

O

O O

O

H

HOO

(116)

O

O

H

O

O

(117) H(118) OH

H

O

O

H

OO

O

H

O

O

H

OHO

HO

O

H

OO

O

O

HO

HO

O

A

B

(121) H A(122) B

O

O

H

OH

H

O

HO

H

(123)

O

O

H

OH

H

O

HO

H

O

OHHOHO

(124)

OHO

O

O

O

H

O

HH

ORO

(125) R = H(126) R = Glc

HO

(127)

OCH3

COOCH3

OCH3

OR1

H3CO

H3CO

H3CO

OR1

OCH3

(120) R1 = 120573-D-Glc

OCH3

(114) R = 120573-D-Glc-

H3CO

R1

OR1

R2

H3CO

R2

OR1

R2R1

OCH3

OCH3

R2

120573-D-Glc-(1rarr6)-120573-D-Glc

H3CO

HOCH2CH2CH2

(6rarr1)-120573-D-Glc (119) R1 = 120573-D-Glc120573-Glc120573-Glc

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 21

H

HHO

(128)

H

OH

(129)

O

O

O

OHHO

HO

OOHO

OH OH(130)

O

OH

(131)O

O OOH

OHHO

(132)

OH

O

H

HO

HH

OR

(133) R = 120573-D-Glc(134) R = H(135) R = tetra-O-acetyl-120573-D-Glc

HO

OO

HO OHOH

OO

OHOH

OH

(136)

N+

H H H(138) Me Me

Me

MeMe

H H H(139) H H H H(140) H OH Me(141) Me H OH Me(142) H H H Me(143) Me OH Me(144) H H Me Me(145) Me H H Me(146) H Me H Me(147) H Me H H(148) Me H H H(149) Me Me H H(150) Me Me H H Me(151) Me Me H Me

MeMeMeMeMeMeMeMeMe

Me

Me

N+

MeO

HOOMe

OMe

(152)

N

MeO

HO

OHH

(153)

N+

HO

(154)

N

OH

HO

+

(155)

+N

O

O

(156)

N

H

+N N

HCHO

OOHO

HO HOOH

(162)

OCH3

+

OCH3

OCH3

H3COOCH3

OCH3

H3CO

H3CO

OCH3

R1

R2

OCH3 H3CO

R1

R2

R3

(157) R1 = R2 = OH(158) R1 = R2 = OMe

R1 R2 R3 R4 R5

OR4

OR5

R1O

R3

R2O

H3CO

(161) R1 = COMe(160) R1 = CHO(159) R1 = CHO

R2 = R3 = OMeR2 = R3 = OMeR2 = R3 = O-CH2-O

(137) -CH2-O

Me2

Figure 1 Continued

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

22 Evidence-Based Complementary and Alternative Medicine

N O

H

O

O

(163)

N+RO

HO

(164) R = H(165) R = Me

N+

OH

O

O

OH

R

(166) R = Me(167) R = H

N

H

+

OHHO

(168)

NH

OH

HO

HO

(169)

N

NN

NH

(170)

N

NN

NO

OH OH

HO

(171)

N

NH

OHO

OH OH

O

O

(172)

NH

HO

HO

(173) (174)

NHO

OH

OH

H

+ Me

OH

(175) (176)

HO

O

N

H

OH

(177)

O N

H

HO

OHN

OOR

RO

(178) R = Ac

H

(179)

N O

N O

(180)

+

NH

OH

HO

O

HO

OH

OH

(182) (183)

O O

O

O

(181)

H3CO

H3CO

Me2

H3CO

OCH3

NH2

NH2

H3CO

NH2

H3CO

H3CO

OCH3

H3CO

H3COH3CO

H3CO OCH3

(CH2)15CH3

(CH2)20CH3HOCH2CH2N(CH3)3Clminus

ClO4+

Figure 1 Continued

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 23

O

OOR

(185) R = OH(186) R = OGlc

O

O

HO

OH

OH

R

(187)

O

O

HO

OH

OH

OGlc

OH

OHO

OH

H

HOH

OH

OH

(188)

OH

OH

HO

OH

(189)

O

OH

HO

OH

(190)

OOH

OHOHHO

O

OH

OHO HO

OH

OH

(191)

HO

OH

OO

HOOH

OH

(192)

HO

OH

(193)

OO

HOOH

OH

(194)

OHO

OH

OH

O

O

HH

(195)

O

OOR

RO

(196) R = 120573-D-Glc

O

O

HH

(197)

O

OH

HO

OH

(198)

HO

OGlc

O

OH

(199)

OHOHO

OH

OH

OHO OHOOH

OH

OHO

OH

HO OO

OHOH

HOOH

(201)

H3CO

OCH3

H3CO

H3CO

H3CO

H3CO

(184) R = CH2-CH = CH2

OCH3

CH2OH

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2OH

OCH3

CH2ORH3CO

OCH3

OCH3

H3CO

OCH3

OCH3

OCH3

OCH3 OCH3OCH3

OCH3

H3CO

H3CO

H3CO

H3COH3CO

H3CO

H3CO

H3CO

H3CO

H3COH3CO

H3CO

(200) R = 120573-D-Api

Figure 1 Continued

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Oxidative Medicine and Cellular Longevity

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

24 Evidence-Based Complementary and Alternative Medicine

O

HO

OH

O

(202)

O

HOO

(203) (204)

GlcO

O OH

O

OOH

OH

HO

OHO

HOHO

O

OOH

OH

OO

OHHO

HORO

HO

(209)

O

(210)

O

OH

HO

OHOH

H

H

H

H

HO

H

(211)

R

O

OH

OH

OH

H

OH

OH

O

RO

HOH

OH

OHHO

(216) R = 120573-D-Glc

OHHO

OH

O

(217) (S)-OH (R)-OH(218) H (S)-OH(219) H (R)-OH(220) H Glc

OH

OH

O

HO

HOHO

O O

(221)

OH

HO

OH

O

HO

HOH

H

OH

OH

(222)

HO

OH

O

HO

HOH

H

OH

OH

(223)

H3CO

OCH3

(CH2)22CH3(CH2)21CH3

R2

(208) R1 = (E)-p-cin(207) R = (E)-fer

R2R1

R1

OR1

R1 = (E)-sin(205)(206) R1 = (E)-p-cou

R2 = OHR2 = H

(215) R = R1 = 120573-OH(214) R = H R1 = 120573-OGlc(213) R = H R1 = 120572-OH(212) R = H R1 = 120573-OH R1 R2

Figure 1 The structures of compounds isolated from Tinospora

Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

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Evidence-Based Complementary and Alternative Medicine

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Evidence-Based Complementary and Alternative Medicine 25

and the lactone ring linking between C-6 and C-8 is quiteremarkable [117 118] Compounds 121-122 fromT crispahavethe same nucleus structure as compound 117rsquos Compounds123ndash126 are rearranged clerodane diterpene obtained fromthe stems of T baenzigeri of which baenzigeride (123) andbaenzigeroside (124) as the novel skeleton arising fromthe cis-ent-neo-clerodane epoxide are considered to be theprecursor of compounds 125 and 126 [119]

412 Other Terpenes There are ten compounds in this cate-gory involving three triterpenoids (127ndash129) six sesquiter-penoids (130ndash135) and one monoterpenoid (136) Cycloe-uphordenol is a novel 31-nortriterpene in T malabarica Theother two new triterpenes are cycloeucalenol and cycloeu-calenone producing mild cardiotonic effects [120] A newrearranged cadinane sesquiterpene glycoside tinosinensideis tested to have inhibitory activities against R-glucosidase[101] Tinocordiside consisting of a tricyclic skeleton witha cyclobutane ring is found in the aqueous fraction ofT cordifolia [61 121] Compounds 133ndash135 possessing thecore structure of the parallelized five-membered and seven-membered rings are new daucane-type sesquiterpenes [122]Compound 136 is the only monoterpenoid isolated from themethanol extract of T cordifolia [94]

42 Alkaloids421 Berberine Alkaloids Twenty berberine alkaloids fromgenus Tinospora have been reported (137ndash156) Commonlythe exact positions of methoxy groups are linked at C-2 C-3 C-9 and C-10 Rings C and D are coplanar with each otherand in good conjugation yet ringsA andB are not in the sameplane because of the saturated carbons at C-5 and C-6 If themethyl linked at C-2 or C-3 is lost it cannot be well stabilizedby the vicinal unsaturated ring C When the methyl is lostfrom C-9 a stable intermediate could be formed After theloss of two H atoms at C-5 and C-6 (rings A and B are in aplane at this time) the two methoxy groups at C-2 and C-3can also turn into a methylenedioxy group [139]The polarityof the overall compound interrelates with the inhibitory ofcholinesterases [86]

422 Aporphine Alkaloids Nine (157ndash165) aporphine alka-loids are isolated and characterized in this genus Whenthe hydroxyl is at C-1 it seems more favorable that theH2O-group tends to be lost in successive fragmentation

Possessing two pairs of vicinal hydroxyl and methoxy groups(usually between C-1 and C-2 and C-10 and C-11) twomolecules of methanol moieties tend to be lost consecutivelyIn mass spectrometry the losses of methyls and the secondmolecule of methanol may as well be considered to be minorfragmentation Such changes may be related to the stericinteractions between the hydroxyl at C-1 and the epoxygroup at C-10 and C-11 Meanwhile the stable aromatic ringprevents diversifications in the core structure [139]

423 Other Alkaloids Compounds 166ndash169 are benzyliso-quinoline alkaloids which play a significant role as a minute

part Compounds 170ndash174 from T crispa acted in concerton the cardiovascular system of anesthetized rats [142 143]Compounds 175ndash178 are homologous provided with identi-cal basic skeleton [149 150]

43 C6-C3 and C6-C3-C6 Constituents Other componentsisolated from the genus include six flavonoids ten lignansand several others [94 103 140] Compounds 183ndash188belonging to flavonoid are the antioxidant profile of genusTinospora It is noteworthy that (minus) epicatechin was reportedfor the first time in the stem extract of T cordifolia [145]Compounds 189ndash198 are lignan inwhich 192ndash194were testedhaving obvious antioxidant activity [112] Syringin (199)isolated from the crude butanol extract of T crispa acted inconcert with other active ingredients on the cardiovascularsystem [142] Tinoscorside D (200) was isolated and eluci-dated based on spectroscopic data from the methanol extractof T cordifolia aerial parts [94]

44 Steroids Tinospora plants also contain steroids that areusually encountered in natural sources and those presentedin genus Tinospora are mostly derivatives of 120573-sitosterol Upto now fifteen of this kind of ingredients have been isolatedand identified Among them 120573-sitosterol and 120573-sitosterylglucosidewere frequently found inTinospora species [110 113139 144]

45 Polysaccharides In the last decades polysaccharides fromgenus Tinospora have caught a great deal of attention due totheir broad spectrum of therapeutic properties and relativelylow toxicity particularly being immune-enhancing agentsThe composition of polysaccharides from T cordifolia wasreported as follows glucose 980 arabinose 05 xylose08 galactose 03 rhamnose 02 and mannose 02[151 152]Through subjecting to GC-MS analysis the types ofmonosaccharidesrsquo linkages were investigated to be terminal-glucose 4-xylose 4-glucose 46-glucose and 2346-glucose[153] Sharma et al reported that the active polysaccharidefractions mainly constitute glucose fructose and arabinoseas monomer units The polymorphonuclear leukocyte func-tion test concluded that they were responsible for immuneenhancement [135] Administration of the polysaccharidefraction from T cordifolia with tumor challenge inhibited(720) the metastases formation in the lungs of syngeneicC57BL6 mice [154] Bioassay guided fractionation and sep-aration of the ethanolic extract of T crispa leaf led to fouracylated glycosylflavonoids Among the isolated compoundsisovitexin 210158401015840-(E)-p-coumarate (206) showed the best activityagainst 120572-glucosidase with an IC

50value of 43plusmn14 120583M[146]

5 Metabolism and Pharmacokinetics

Todate there are fewpharmacokinetics studies of the extractsof this genus Previous pharmacokinetics studies ofTinosporamainly focused on its diterpenes and its derived compoundsthat fitted to a one-compartment model Shi et al reportedthat columbin (75) and its derivatives (72 74 80 and 83) arecommonly present in the root of T capillipes and T sagittata

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

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Computational and Mathematical Methods in Medicine

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Research and TreatmentAIDS

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

26 Evidence-Based Complementary and Alternative Medicine

Columbin is the major urinary metabolites in rats to whichthese compounds were orally given These componentscould be absorbed and metabolized by the gastrointestinaltract But pharmacokinetic studies showed that absorptionof diterpene components was poorly absorbed throughthe gastrointestinal tract and they were quickly eliminatedOwing to the similar structures these compounds haveparallel pharmacokinetic parameters in vivo Columbin iseliminated with systemic clearance of 504plusmn 292 Lhkg afteriv administration demonstrating a little higher blood flowrate (33 Lhkg in rats) than the hepar It could be concludedthat columbin was rapidly cleared via hepatic clearance andextrahepatic clearanceThevolumeof distribution at terminalphase was 873 plusmn 311 Lkg demonstrating a much highertotal body water of 067 LkgThe above researches suggestedthat columbin has extensive distribution into extravascularsystems Because columbin is almost insoluble in water theabsolute oral bioavailability of columbin is only 318plusmn 222The time to reach the maximum plasma drug concentrationis less than 5mins The aforementioned indicate that theabsorption of columbin is limited and quickly eliminated[107 155 156] So it is necessary to improve its absorptionin vivo for clinical application in further research on phar-maceutical preparation Since few pharmacokinetics studiesof the extracts of Tinospora species have been reported theneeds formechanismof actions on themare necessary in viewof the wide bioactivities and extensive uses and metabolismand pharmacokinetics studies are warranted to find out itsmost perspective activities

6 Safety Evaluation

The clinical existence for herbs of genus Tinospora overcenturies are in a way themselves evidences of therapeuticutility No adverse effects have been reported in this genusprescribed under reasonable doses application T cordifoliais advocated as a tonic in infants and children to facilitategrowth The LD

50value for T cordifolia is higher than 1 gkg

for oral administration [157] Acute toxicity study with thedose of 3 gkg demonstrated that T cordifolia does not haveany side effects and reported no death of the experimentalrats [158] When administered in doses of 01 gkg for 12weeks T cordifolia does not trigger any unfavorable factorson liver and renal function parameters in rats It precipitatedthe increment of leukocytosis with neutrophilia in rats whileno such effect was observed in healthy humans [27 159]T cordifolia treatment does not display clastogenicity andDNA damaging effect in bone marrow erythrocytes andperipheral blood lymphocytes [160] And no neurologicalimpairment or marked central nervous system depressantactivities were shown [161] Administration of T cordifoliato healthy volunteers has been found to be safe in phase Istudy and the drug was well tolerated [157 162] It has alsobeen shown not to exert any conspicuous adverse reactionson the gastrointestinal system renal system cardiovascularsystem and central nervous system [163] However sys-tematic toxicological tests and safety evaluations have notbeen carried out extensively within the Tinospora speciesGenerally speaking it could be used safely at low and middle

dosage Since test for toxicology of chemical constituents inthis genus are rare until now more toxicity researches remainto be done

7 Conclusions

The review paper summarized a total of 223 compounds andabundant clerodane-type diterpene components that werereported from the genus Tinospora with 152 references citedWe noted that Tinospora has an extensive distribution tar-geted clinical application and diverse biological and pharma-cological activities of pure compounds and extracts Previousphytochemical researches on the genus revealed the extensivepresence of terpenoid alkaloid C

6-C3derivative polysac-

charide and other compound types The pharmacologicalactivities were mainly regarded on antidiabetic antioxidantantitumor anti-inflammatory antimicrobial antiosteoporo-sis and immunostimulation activities From the review it canbe seen that phytochemical investigations pharmacologicalresearches and traditional clinical application mainly focuson 4 Tinospora species T sagittata T capillipes T cordifoliaand T crispa The related chemical and biological activitiestoward other Tinospora species are still blank So plentyof further studies are necessary in order to illustrate thechemodiversity and to make full use of the biological signifi-cance of the compounds and extracts of Tinospora especiallythe antidiabetic and antioxidant activities Future workswill be focused on the following aspects to use Tinosporaspecies as chemopreventive and therapeutic agent for variousdiseases or to use them as adjuncts to exiting drugs tothe treatment of diabetes or to discover important andinteresting biologically active compounds from these herbsby bioactivity-guided isolation The authors wish the reviewcan provide valuable data for explorations and advancedresearches of Tinospora species

Competing Interests

The authors confirm that this paperrsquos content has no conflictof interests

Acknowledgments

The authors would also like to express their gratitude toBeijing University of Chinese Medicine for financial supportof this paper

References

[1] P A Shah and G B Shah ldquoPreliminary screening of Tinosporacordifolia extracts and guduchi satva for anti-rheumatoid activ-ityrdquo International Journal for Pharmaceutical Research Scholarsvol 5 no 2 pp 7ndash13 2016

[2] Committee for the Pharmacopoeia of PR China Pharma-copoeia of PR China Part I China Medical Science andTechnology Press Beijing China 2015

[3] R Sharma H Amin Galib and P K Prajapati ldquoAntidia-betic claims of Tinospora cordifolia (Willd) Miers critical

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

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PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

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Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 27

appraisal and role in therapyrdquo Asian Pacific Journal of TropicalBiomedicine vol 5 no 1 pp 68ndash78 2015

[4] J Z Yuan Studies on the Constituents of Smilax glabra Roxband Tinospora sinensis (Lour) Merr Shenyang PharmaceuticalUniversity Shenyang China 2004

[5] N Ilaiyaraja and F Khanum ldquoAntioxidant potential ofTinospora cordifolia extracts and their protective effect onoxidation of biomoleculesrdquo Pharmacognosy Journal vol 3 no20 pp 56ndash62 2011

[6] M I Khan P S C S Harsha P Giridhar and G ARavishankar ldquoPigment identification antioxidant activity andnutrient composition of Tinospora cordifolia (willd) Miers exHook f amp Thoms fruitrdquo International Journal of Food Sciencesand Nutrition vol 62 no 3 pp 239ndash249 2011

[7] G Thippeswamy and B P Salimath ldquoInduction of caspase-3 activated DNase mediated apoptosis by hexane fraction ofTinospora cordifolia in EAT cellsrdquoEnvironmental Toxicology andPharmacology vol 23 no 2 pp 212ndash220 2007

[8] P Kapur B M J Pereira W Wuttke and H Jarry ldquoAndrogenicaction of Tinospora cordifolia ethanolic extract in prostatecancer cell line LNCaPrdquo Phytomedicine vol 16 no 6-7 pp 679ndash682 2009

[9] R W Li D N Leach S P Myers et al ldquoAnti-inflammatoryactivity cytotoxicity and active compounds of Tinospora smi-lacina Benthrdquo Phytotherapy Research vol 18 no 1 pp 78ndash832004

[10] M Tiwari U N Dwivedi and P Kakkar ldquoTinospora cordifoliaextract modulates COX-2 iNOS ICAM-1 pro-inflammatorycytokines and redox status in murine model of asthmardquo Journalof Ethnopharmacology vol 153 no 2 pp 326ndash337 2014

[11] F Bonvicini M Mandrone F Antognoni F Poli and GA Gentilomi ldquoEthanolic extracts of Tinospora cordifolia andAlstonia scholaris show antimicrobial activity towards clinicalisolates of methicillin-resistant and carbapenemase-producingbacteriardquo Natural Product Research vol 28 no 18 pp 1438ndash1445 2014

[12] R Gowrishankar M Kumar V Menon et al ldquoTrace elementstudies on Tinospora cordifolia (Menispermaceae) Ocimumsanctum (Lamiaceae) Moringa oleifera (Moringaceae) andPhyllanthus niruri (Euphorbiaceae) using PIXErdquo BiologicalTrace Element Research vol 133 no 3 pp 357ndash363 2010

[13] M SenguptaGD Sharma andBChakraborty ldquoEffect of aque-ous extract of Tinospora cordifolia on functions of peritonealmacrophages isolated fromCCl4 intoxicatedmale albinomicerdquoBMC Complementary and Alternative Medicine vol 11 article102 2011

[14] W Z Qin H W Wei and Z H Zhang ldquoThe observation ofcurative effect on knee osteoarthritis through intra-articularinjection of traditional Chinese drug ion-introduction coupledwith triamcinolone acetonide about 78 casesrdquo New Journal ofTraditional Chinese Medicine vol 38 no 10 pp 36ndash37 2006

[15] Z N Liu ldquoQutan tongluo reciperdquo Guangxi Journal of Tradi-tional Chinese Medicine vol 27 no 3 p 44 2004

[16] H S Zhang LM Zhang andHH Zhang ldquoThe observation ofcurative effect of knee ankylosis after injury auxiliary throughhuoxue Shujin Xunxi reciperdquo Shaanxi Journal of TraditionalChinese Medicine vol 31 no 8 pp 997ndash998 2010

[17] L D Wang L Huang B M Zhao and K H Zhang ldquoTheobservation of curative effect of adult humeral shaft fracturethrough integrated traditional Chinese and western medicinetreatmentrdquoNew Journal of Traditional Chinese Medicine vol 37no 10 pp 59ndash60 2005

[18] MX Chen Z R Li andM Z Liang ldquoTreatment for supine andprone external ratationed ankle fracturerdquo Journal of GuangzhouUniversity of Traditional Chinese Medicine vol 24 no 6 pp456ndash458 2007

[19] N Singh A Kumar P Gupta et al ldquoEvaluation of antileishma-nial potential ofTinospora sinensis against experimental visceralleishmaniasisrdquoParasitology Research vol 102 no 3 pp 561ndash5652008

[20] S J Li J Cheng Y Q Han and X J Liu ldquoThe preparationand clinical application of Jinguo mixturerdquo Chinese TraditionalPatent Medicine vol 31 no 3 pp 6ndash7 2009

[21] H Y Zhang andW F Han ldquoThe treatment of infusion phlebitisusing immersion liquid of Tinospora capillipes on 78 casesrdquoJournal of ExternalTherapy of Traditional ChineseMedicine vol8 no 6 p 25 1999

[22] W K Liu Y F Zhao and B Y Guan ldquoThe preparation andapplication of Tinospora capillipesrdquo Jilin Journal of TraditionalChinese Medicine no 6 p 31 1990

[23] T Z Wang L L Du and C Bai ldquoThe research progress ofTinospora capillipesrdquo Journal of ChineseMedicinalMaterials vol25 no 4 pp 292ndash294 2002

[24] F X Li ldquoApplication research of Tinospora capillipes in veteri-narianrdquo Sichuan Animal ampVeterinary Sciences no 11 pp 26ndash272009

[25] F R Wu C Y Zeng and W B Dai ldquoPharmacological effectsof Tinospora sinensis and research progress in its clinicalapplicationrdquo China Licensed Pharmacist vol 11 no 12 pp 37ndash40 2014

[26] J Zeng X R Zeng and H Y Guan ldquoA comparative study ofthree medicine for Tinospora sinensisrdquo Journal of Medicine ampPharmacy of Chinese Minorities no 10 pp 38ndash39 2008

[27] T S Panchabhai U P Kulkarni and N N Rege ldquoValidation oftherapeutic claims of Tinospora cordifolia a reviewrdquo Phytother-apy Research vol 22 no 4 pp 425ndash441 2008

[28] N Choudhary M B Siddiqui S Azmat and S KhatoonldquoTinospora cordifolia ethnobotany phytopharmacology andphytochemistry aspectsrdquo International Journal of Pharmaceuti-cal Sciences and Research vol 4 no 3 pp 891ndash899 2013

[29] Y R Sohni and R M Bhatt ldquoActivity of a crude extract formu-lation in experimental hepatic amoebiasis and in immunomod-ulation studiesrdquo Journal of Ethnopharmacology vol 54 no 2-3pp 119ndash124 1996

[30] S A Tasaduq K Singh S Sethi et al ldquoHepatocurativeand antioxidant profile of HP-1 a polyherbal phytomedicinerdquoHuman and Experimental Toxicology vol 22 no 12 pp 639ndash645 2003

[31] H Purandare and A Supe ldquoImmunomodulatory role ofTinospora cordifolia as an adjuvant in surgical treatment ofdiabetic foot ulcers a prospective randomized controlled studyrdquoIndian Journal of Medical Sciences vol 61 no 6 pp 347ndash3552007

[32] V A Badar V R Thawani P T Wakode et al ldquoEfficacy ofTinospora cordifolia in allergic rhinitisrdquo Journal of Ethnophar-macology vol 96 no 3 pp 445ndash449 2005

[33] Y R Sohni P Kaimal and R M Bhatt ldquoThe antiamoebiceffect of a crude drug formulation of herbal extracts againstEntamoeba histolytica in vitro and in vivordquo Journal of Ethnophar-macology vol 45 no 1 pp 43ndash52 1995

[34] A Chopra M Saluja G Tillu et al ldquoComparable efficacy ofstandardized Ayurveda formulation and hydroxychloroquinesulfate (HCQS) in the treatment of rheumatoid arthritis (RA)

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

28 Evidence-Based Complementary and Alternative Medicine

a randomized investigator-blind controlled studyrdquo ClinicalRheumatology vol 31 no 2 pp 259ndash269 2012

[35] D Krishnaiah R Sarbatly and R Nithyanandam ldquoA review ofthe antioxidant potential of medicinal plant speciesrdquo Food andBioproducts Processing vol 89 no 3 pp 217ndash233 2011

[36] S Jain B Sherlekar and R Barik ldquoEvaluation of antioxidantpotential of Tinospora cordifolia and Tinospora sinensisrdquo Inter-national Journal of Pharmaceutical Sciences and Research vol 1no 11 pp 122ndash128 2010

[37] M Sarala V Velu C Anandharamakrishnan and R P SinghldquoSpray drying of Tinospora cordifolia leaf and stem extract andevaluation of antioxidant activityrdquo Journal of Food Science andTechnology vol 49 no 1 pp 119ndash122 2012

[38] A Cavin K Hostettmann W Dyatmyko and O PotteratldquoAntioxidant and lipophilic constituents of Tinospora crispardquoPlanta Medica vol 64 no 5 pp 393ndash396 1998

[39] D Naik C Dandge and S Rupanar ldquoDetermination of chemi-cal composition and evaluation of antioxidant activity ofessential oil from Tinospora cordifolia (Willd) Leafrdquo Journal ofEssential Oil-Bearing Plants vol 17 no 2 pp 228ndash236 2014

[40] L S Duvvuri S Katiyar A Kumar and W Khan ldquoDeliveryaspects of antioxidants in diabetes managementrdquo Expert Opin-ion on Drug Delivery vol 12 no 5 pp 827ndash844 2015

[41] T Klangjareonchai S Putadechakum and C Roongpisuthi-pong ldquoReview of anti-hyperglycemic effect ofTinospora crispardquoWalailak Journal of Science and Technology vol 12 no 5 pp403ndash406 2015

[42] C-T Ruan S-H Lam T-C Chi S-S Lee and M-J SuldquoBorapetoside C from Tinospora crispa improves insulin sensi-tivity in diabetic micerdquo Phytomedicine vol 19 no 8-9 pp 719ndash724 2012

[43] C-T Ruan S-H Lam S-S Lee and M-J Su ldquoHypoglycemicaction of borapetoside A from the plant Tinospora crispa inmicerdquo Phytomedicine vol 20 no 8-9 pp 667ndash675 2013

[44] F E Lokman H F Gu W N Wan Mohamud M M YusoffK L Chia and C-G Ostenson ldquoAntidiabetic effect of oralborapetol B compound isolated from the plant Tinosporacrispa by stimulating insulin releaserdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2013 Article ID 7276027 pages 2013

[45] S Mishra N Verma S Bhattacharya et al ldquoEffect of Tinosporacordifolia as an add-on therapy on the blood glucose levels ofpatients with type 2 diabetesrdquo International Journal of Basic ampClinical Pharmacology vol 4 no 3 pp 537ndash541 2015

[46] S Mishra N Verma S Bhattacharya et al ldquoEfficacy and safetyofTinospora cordifolia (Tc) as an add-on therapy in patientswithtype-2 diabetesrdquo International Journal of Research in MedicalSciences vol 3 no 5 pp 1109ndash1113 2015

[47] M B Patel and S M Mishra ldquoMagnoflorine from Tinosporacordifolia stem inhibits 120572-glucosidase and is antiglycemic inratsrdquo Journal of Functional Foods vol 4 no 1 pp 79ndash86 2012

[48] R Kannadhasan and S Venkataraman ldquoIn vitro capacity andin vivo antioxidant potency of sedimental extract of Tinosporacordifolia in streptozotocin induced type 2 diabetesrdquo AvicennaJournal of Phytomedicine vol 3 no 1 pp 7ndash24 2013

[49] N Puranik S Devi Devi and K Kammar ldquoHyperactivationof the hypothalamo-pituitary-Adrenocortical axis in streptozo-tocin diabetic rats effect of Tinospora cordifolia (Willd) andinsulin therapyrdquo Turkish Journal of Medical Sciences vol 42 no6 pp 1076ndash1081 2012

[50] P K Gupta P Chakraborty S Kumar et al ldquoG1-4A apolysaccharide from Tinospora cordifolia inhibits the survivalof Mycobacterium tuberculosis by modulating host immuneresponses in TLR4 dependent mannerrdquo PLoS ONE vol 11 no5 Article ID e0154725 2016

[51] K Ohtani K Okai U Yamashita I Yuasa and A MisakildquoCharacterization of an acidic polysaccharide isolated from theleaves of Corchorus olitorius (Moroheiya)rdquo Bioscience Biotech-nology and Biochemistry vol 59 no 3 pp 378ndash381 1995

[52] E A Velazquez D Kimura D Torbati C Ramachandran andB R Totapally ldquoImmunological response to (14)-120572-D-glucanin the lung and spleen of endotoxin-stimulated juvenile ratsrdquoBasic and Clinical Pharmacology and Toxicology vol 105 no 5pp 301ndash306 2009

[53] R Koppada F M Norozian D Torbati S Kalomiris CRamachandran and B R Totapally ldquoPhysiological effects of anovel immune stimulator drug (14)-120572-d-glucan in ratsrdquo Basicand Clinical Pharmacology and Toxicology vol 105 no 4 pp217ndash221 2009

[54] V Aher and A K Wahi ldquoBiotechnological approach toevaluate the immunomodulatory activity of ethanolic extractof Tinospora cordifoliastem (mango plant climber)rdquo IranianJournal of Pharmaceutical Research vol 11 no 3 pp 863ndash8722012

[55] P K R Nair S Rodriguez R Ramachandran et al ldquoImmunestimulating properties of a novel polysaccharide from themedicinal plant Tinospora cordifoliardquo International Immuno-pharmacology vol 4 no 13 pp 1645ndash1659 2004

[56] V K Pandey B S Shankar and K B Sainis ldquoG1-4 Aan arabinogalactan polysaccharide from Tinospora cordifoliaincreases dendritic cell immunogenicity in amurine lymphomamodelrdquo International Immunopharmacology vol 14 no 4 pp641ndash649 2012

[57] G Chintalwar A Jain A Sipahimalani et al ldquoAn immunolog-ically active arabinogalactan from Tinospora cordifoliardquo Phyto-chemistry vol 52 no 6 pp 1089ndash1093 1999

[58] R Raghu D Sharma R Ramakrishnan S Khanam G JChintalwar and K B Sainis ldquoMolecular events in the activationof B cells and macrophages by a non-microbial TLR4 agonistG1-4A from Tinospora cordifoliardquo Immunology Letters vol 123no 1 pp 60ndash71 2009

[59] U Bhardwaj B K Tiwary A Prasad and S Ganguly ldquoEffectof Tinospora cordifolia extract on immune response and serumbiochemical profile in broilersrdquo Indian Journal of AnimalSciences vol 82 no 4 pp 379ndash381 2012

[60] C P Alexander C J W Kirubakaran and R D MichaelldquoWater soluble fraction of Tinospora cordifolia leaves enhancedthe non-specific immunemechanisms and disease resistance inOreochromis mossambicusrdquo Fish amp Shellfish Immunology vol29 no 5 pp 765ndash772 2010

[61] U Sharma M Bala N Kumar B Singh R K Munshiand S Bhalerao ldquoImmunomodulatory active compounds fromTinospora cordifoliardquo Journal of Ethnopharmacology vol 141 no3 pp 918ndash926 2012

[62] W N Abood I Fahmi M A Abdulla and S Ismail ldquoIm-munomodulatory effect of an isolated fraction from Tinosporacrispa on intracellular expression of INF-120574 IL-6 and IL-8rdquo BMCComplementary and Alternative Medicine vol 14 no 1 article205 2014

[63] A Kapil and S Sharma ldquoImmunopotentiating compoundsfrom Tinospora cordifoliardquo Journal of Ethnopharmacology vol58 no 2 pp 89ndash95 1997

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

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Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 29

[64] S Jiang L M Qiu L Li et al ldquoEffects ofMarsdenia tenacissimapolysaccharide on the immune regulation and tumor growth inH22

tumor-bearing micerdquo Carbohydrate Polymers vol 137 pp52ndash58 2016

[65] P M P Ferreira G C G Militao D J B Lima et al ldquoMor-phological and biochemical alterations activated by antitumorclerodane diterpenesrdquoChemico-Biological Interactions vol 222pp 112ndash125 2014

[66] A M Prieto A G dos Santos A P S Oliveira et al ldquoAssess-ment of the chemopreventive effect of casearin B a clerodanediterpene extracted from Casearia sylvestris (Salicaceae)rdquo Foodand Chemical Toxicology vol 53 pp 153ndash159 2013

[67] P R F De Carvalho M Furlan M C M Young D G IKingston and V D S Bolzani ldquoAcetylated DNA-damagingclerodane diterpenes from Casearia sylvestrisrdquo Phytochemistryvol 49 no 6 pp 1659ndash1662 1998

[68] R Mishra and G Kaur ldquoAqueous ethanolic extract of Tinosporacordifolia as a potential candidate for differentiation basedtherapy of glioblastomasrdquo PLoS ONE vol 8 no 10 Article IDe78764 pp 1ndash13 2013

[69] P More and K Pai ldquoIn vitro NADH-oxidase NADPH-oxidaseand myeloperoxidase activity of macrophages after Tinosporacordifolia (guduchi) treatmentrdquo Immunopharmacology andImmunotoxicology vol 34 no 3 pp 368ndash372 2012

[70] J W Liang T J Zhang Z J Li Z X Chen X L Yan and FH Meng ldquoPredicting potential antitumor targets of Aconitumalkaloids by molecular docking and protein-ligand interactionfingerprintrdquo Medicinal Chemistry Research vol 25 no 6 pp1115ndash1124 2016

[71] H Ali and S Dixit ldquoExtraction optimization of Tinosporacordifolia and assessment of the anticancer activity of its alkaloidpalmatinerdquo The Scientific World Journal vol 2013 Article ID376216 10 pages 2013

[72] P K R Nair S J Melnick R Ramachandran E Escalon andC Ramachandran ldquoMechanism of macrophage activation by(14)-120572-d-glucan isolated from Tinospora cordifoliardquo Interna-tional Immunopharmacology vol 6 no 12 pp 1815ndash1824 2006

[73] V Sonaimuthu S Krishnamoorthy and M Johnpaul ldquoTaxolproducing endophytic fungus Fusarium culmorum SVJM072from medicinal plant of Tinospora cordifoliamdasha first reportrdquoJournal of Biotechnology vol 150 supplement p 425 2010

[74] A Jungbauer and SMedjakovic ldquoAnti-inflammatory propertiesof culinary herbs and spices that ameliorate the effects ofmetabolic syndromerdquoMaturitas vol 71 no 3 pp 227ndash239 2012

[75] Q Xu Y Wang S Guo Z Shen Y Wang and L Yang ldquoAnti-inflammatory and analgesic activity of aqueous extract of Flospopulirdquo Journal of Ethnopharmacology vol 152 no 3 pp 540ndash545 2014

[76] Y C Deng M Zhang and H Y Luo ldquoIdentification andantimicrobial activity of two alkaloids from traditional Chinesemedicinal plant Tinospora capillipesrdquo Industrial Crops andProducts vol 37 no 1 pp 298ndash302 2012

[77] M F Khalilsaraie N Saima N T Meti R K Bhadekar andD P Nerkar ldquoCytological study and anti-microbial activity ofembryogenic callus induced from leaf cultures of Tinosporacordifolia (Willd) Miersrdquo Journal of Medicinal Plant Researchvol 5 no 14 pp 3002ndash3006 2011

[78] JM BhagyasreeH J Hrishikeshavan P Krishnamoorthy et alldquoCytoprotective influence of ethanolic stem extract ofTinosporacardifolia on the inflammatory bowel diseaserdquo InternationalJournal of Advanced Research vol 4 no 4 pp 179ndash187 2016

[79] N-D Zhang T Han B-K Huang et al ldquoTraditional Chi-nese Medicine formulas for the treatment of osteoporosisimplication for antiosteoporotic drug discoveryrdquo Journal ofEthnopharmacology vol 189 pp 61ndash80 2016

[80] L Gao G P Cai and X J Shi ldquo120573-ecdysterone inducesosteogenic differentiation in mouse mesenchymal stem cellsand relieves osteoporosisrdquo Biological and Pharmaceutical Bul-letin vol 31 no 12 pp 2245ndash2249 2008

[81] G Abiramasundari K R Sumalatha andM Sreepriya ldquoEffectsof Tinospora cordifolia (Menispermaceae) on the proliferationosteogenic differentiation and mineralization of osteoblastmodel systems in vitrordquo Journal of Ethnopharmacology vol 141no 1 pp 474ndash480 2012

[82] A Patel P Bigoniya C S Singh and N S Patel ldquoRadiopro-tective and cytoprotective activity of Tinospora cordifolia stemenriched extract containing cordifolioside-Ardquo Indian Journal ofPharmacology vol 45 no 3 pp 237ndash243 2013

[83] L Singh S Tyagi M A Rizvi and H C Goel ldquoEffect ofTinospora cordifolia on gamma ray-induced perturbations inmacrophages and splenocytesrdquo Journal of Radiation Researchvol 48 no 4 pp 305ndash315 2007

[84] S K Rao P S Rao and B N Rao ldquoPreliminary investigation ofthe radiosensitizing activity of Guduchi (Tinospora cordifolia)in tumor-bearing micerdquo Phytotherapy Research vol 22 no 11pp 1482ndash1489 2008

[85] H Sachdeva R Sehgal and S Kaur ldquoTinospora cordifolia as aprotective and immunomodulatory agent in combination withcisplatin against murine visceral leishmaniasisrdquo ExperimentalParasitology vol 137 no 1 pp 53ndash65 2014

[86] M Yusoff H Hamid and P Houghton ldquoAnticholinesteraseinhibitory activity of quaternary alkaloids from TinosporacrispardquoMolecules vol 19 no 1 pp 1201ndash1211 2014

[87] J Kosaraju S Chinni P D Roy E Kannan A S Antonyand M N S Kumar ldquoNeuroprotective effect of Tinosporacordifolia ethanol extract on 6-hydroxy dopamine inducedParkinsonismrdquo Indian Journal of Pharmacology vol 46 no 2pp 176ndash180 2014

[88] A Gupta H Raj M S Karchuli and N Upmanyu ldquoCompara-tive evaluation of ethanolic extracts ofBacopamonnieriEvolvu-lus alsinoides Tinospora cordifolia and their combinations oncognitive functions in ratsrdquo Current Aging Science vol 6 no3 pp 239ndash243 2013

[89] J Jiang Z X Liao and M Ji ldquoThe review about structurecharacteristics and NMR data of clerodane-type diterpenoidsrdquoChemical Industry Times vol 21 no 12 pp 49ndash53 2007

[90] S C Butler and C J Forsyth ldquoA stereoconvergent intramolec-ular Diels-Alder cycloaddition related to the construction ofthe decalin core of neo-clerodane diterpenoidsrdquo The Journal ofOrganic Chemistry vol 78 no 8 pp 3895ndash3907 2013

[91] M I Choudhary M Ismail K Shaari et al ldquoCis- clerodane-type furanoditerpenoids from Tinospora crispardquo Journal ofNatural Products vol 73 no 4 pp 541ndash547 2010

[92] L-M Shi R-Q Li and W-H Liu ldquoTwo new furanoid diter-penoids from Tinospora sagittatardquo Helvetica Chimica Acta vol91 no 5 pp 978ndash982 2008

[93] X-Z Huang C-M Cheng Y Dai et al ldquoA novel 18-Norcler-odane diterpenoid from the roots of Tinospora sagittata varyunnanensisrdquoMolecules vol 15 no 11 pp 8360ndash8365 2010

[94] P VanKiem C VanMinhN T Dat et al ldquoAporphine alkaloidsclerodane diterpenes and other constituents from Tinosporacordifoliardquo Fitoterapia vol 81 no 6 pp 485ndash489 2010

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

30 Evidence-Based Complementary and Alternative Medicine

[95] N Fukuda M Yonemitsu and T Kimura ldquoIsolation andstructure elucidation of the new furanoid diterpene glucosideborapetoside Hrdquo Liebigs Annalen der Chemie vol 26 no 50 pp1689ndash1691 1995

[96] Y C Koay and F Amir ldquoA review of the secondary metabolitesand biological activities of Tinospora crispa (Menispermaceae)rdquoTropical Journal of Pharmaceutical Research vol 12 no 4 pp641ndash649 2013

[97] Z Y Jiang W J Li L X Jiao et al ldquoNew clerodane diterpenesfrom Tinospora sagittata var yunnanensisrdquo Planta Medica vol80 no 5 pp 419ndash425 2014

[98] W Li C Huang S P Li et al ldquoClerodane diterpenoids fromTinospora sagittata (Oliv) gagneprdquo Planta Medica vol 78 no 1pp 82ndash85 2012

[99] V Wazir R Maurya and R S Kapil ldquoCordioside a clerodanefurano diterpene glucoside from Tinospora cordifoliardquo Phyto-chemistry vol 38 no 2 pp 447ndash449 1995

[100] V D Gangan P Pradhan A T Sipahimalani and A BanerjildquoNorditerpene furan glycosides from Tinospora cordifoliardquo Phy-tochemistry vol 39 no 5 pp 1139ndash1142 1995

[101] W Li KWei H Fu and K Koike ldquoStructure and absolute con-figuration of clerodane diterpene glycosides and a rearrangedcadinane sesquiterpene glycoside from the stems of Tinosporasinensisrdquo Journal of Natural Products vol 70 no 12 pp 1971ndash1976 2007

[102] F Ahmad M Ali and P Alam ldquoNew phytoconstituents fromthe stem bark of Tinospora cordifolia Miersrdquo Natural ProductResearch vol 24 no 10 pp 926ndash934 2010

[103] L-P Dong C-X Chen W Ni B-B Xie J-Z Li and H-YLiu ldquoA new dinorclerone diterpenoid glycoside from TinosporasinensisrdquoNatural Product Research vol 24 no 1 pp 13ndash17 2010

[104] M Yonemitsu N Fukuda T Kimura R Isobe and T KomorildquoIsolation and structure elucidation of two new dinorditerpeneglucosides tinosineside A and Brdquo Liebigs Annalen vol 1995 no2 pp 437ndash439 1995

[105] C Huang W Li F H Ma Q Li Y Asada and K KoikeldquoTinospinosides D E and Tinospin E further clerodane diter-penoids from Tinospora sagittatardquo Chemical and Pharmaceuti-cal Bulletin vol 60 no 10 pp 1324ndash1328 2012

[106] S Q Rong Y H Shen C Zhang R H Liu and W D ZhangldquoChemical constituents of two original plants used as radixTinosporaerdquo Chinese Journal of Natural Medicines vol 6 no 3pp 186ndash189 2008

[107] Z-J Zhan X-Y Zhang X-R Hou C-P Li and W-G ShanldquoNewditerpenoids fromTinospora capillipesrdquoHelveticaChimicaActa vol 92 no 4 pp 790ndash794 2009

[108] L Pan C Terrazas CM Lezama-Davila et al ldquoCordifolideA asulfur-containing clerodane diterpene glycoside from Tinospo-ra cordifoliardquo Organic Letters vol 14 no 8 pp 2118ndash2121 2012

[109] R Maurya L R Manhas P Gupta P K Mishra G Singhand P P Yadav ldquoAmritosides A B C and D clerodane furanoditerpene glucosides fromTinospora cordifoliardquoPhytochemistryvol 65 no 14 pp 2051ndash2055 2004

[110] M Dhanasekaran A-A Baskar S Ignacimuthu P Agastianand V Duraipandiyan ldquoChemopreventive potential of Epoxyclerodane diterpene from Tinospora cordifolia against diethyl-nitrosamine-induced hepatocellular carcinomardquo InvestigationalNew Drugs vol 27 no 4 pp 347ndash355 2009

[111] P Antonisamy M Dhanasekaran S Ignacimuthu et alldquoGastroprotective effect of epoxy clerodane diterpene isolated

from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in ratsrdquo Phytomedicine vol 21 no 7 pp966ndash969 2014

[112] X-Z Huang C-M Cheng Y Dai et al ldquoA novel lignanglycoside with antioxidant activity from Tinospora sagittata varyunnanensisrdquo Natural Product Research vol 26 no 20 pp1876ndash1880 2012

[113] R Maurya V Wazir A Tyagi and R S Kapil ldquoClerodanediterpenoids fromTinospora cordifoliardquo Phytochemistry vol 38no 3 pp 659ndash661 1995

[114] N L Hungerford D P A Sands and W Kitching ldquoIsolationand structure of some constituents of the Australian medicinalplant Tinospora smilacina (lsquoSnakevinersquo)rdquo Australian Journal ofChemistry vol 51 no 12 pp 1103ndash1111 1998

[115] C Y Ragasa M C Cruz R Gula and J A Rideout ldquoClerodanediterpenes from Tinospora rumphiirdquo Journal of Natural Prod-ucts vol 63 no 4 pp 509ndash511 2000

[116] N Fukuda M Nakamura M Yonemitsu T Kimura R Isobeand T Komori ldquoIsolation and structure elucidation of two newfuranoid diterpenes Tinotufolin A and Brdquo Liebigs Annalen derChemie vol 1993 no 3 pp 325ndash327 1993

[117] T S Martin K Ohtani R Kasai and K Yamasaki ldquoClerodanediterpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 40 no 6 pp 1729ndash1736 1995

[118] T S Martin K Ohtani R Kasai and K Yamasaki ldquoFuranoidditerpene glucosides from Tinospora rumphiirdquo Phytochemistryvol 42 no 1 pp 153ndash158 1996

[119] P Tuntiwachwuttikul and W C Taylor ldquoNew rearrangedclerodane diterpenes from Tinospora baenzigerirdquo Chemical andPharmaceutical Bulletin vol 49 no 7 pp 854ndash857 2001

[120] N Kongkathip P Dhumma-upakorn B Kongkathip KChawananoraset P Sangchomkaeo and S Hatthakitpanich-akul ldquoStudy on cardiac contractility of cycloeucalenol andcycloeucalenone isolated from Tinospora crispardquo Journal ofEthnopharmacology vol 83 no 1-2 pp 95ndash99 2002

[121] S Ghosal and R A Vishwakarma ldquoTinocordiside a newrearranged cadinane sesquiterpene glycoside from Tinosporacordifoliardquo Journal of Natural Products vol 60 no 8 pp 839ndash841 1997

[122] R Maurya K L Dhar and S S Handa ldquoA sesquiterpeneglucoside from Tinospora cordifoliardquo Phytochemistry vol 44no 4 pp 749ndash750 1997

[123] B Wang P-L Zhang M-X Zhou et al ldquoNew nor-clerodane-type furanoditerpenoids from the rhizomes of Tinospora capil-lipesrdquo Phytochemistry Letters vol 15 pp 225ndash229 2016

[124] A Sivasubramanian K K G Narasimha R Rathnasamy andA M F O Campos ldquoA new antifeedant clerodane diterpenoidfrom Tinospora cordifoliardquo Natural Product Research vol 27no 16 pp 1431ndash1436 2013

[125] G Zhang H Ma S Hu et al ldquoClerodane-type diterpenoidsfrom tuberous roots of Tinospora sagittata (Oliv) GagneprdquoFitoterapia vol 110 pp 59ndash65 2016

[126] N Fukuda M Yonemitsu and T Kimura ldquoStudies on the con-stituents of the stems of Tinospora tuberculata BEUMEE III1)newdterpenoids borapetoside B and borapetol BrdquoChemical andPharmaceutical Bulletin vol 34 no 7 pp 2868ndash2872 1986

[127] A U Rahman S S Ali S Ahmad and M I ChoudharyldquoA furanoid diterpene from Tinospora malabaricardquo Phytochem-istry vol 31 no 9 pp 3155ndash3157 1992

[128] N Fukuda M Yonemitsu and T Kimura ldquoIsolation and struc-ture elucidation of the five new furanoid diterpene glycosides

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Evidence-Based Complementary and Alternative Medicine 31

borapetoside C-Grdquo Chemical and Pharmaceutical Bulletin vol24 no 37 pp 156ndash161 1993

[129] S-H Lam C-T Ruan P-H Hsieh M-J Su and S-S LeeldquoHypoglycemic diterpenoids from Tinospora crispardquo Journal ofNatural Products vol 75 no 2 pp 153ndash159 2012

[130] R K Bhatt and B K Sabata ldquoA furanoid diterpene glucosidefrom Tinospora cordifoliardquo Phytochemistry vol 28 no 9 pp2419ndash2422 1989

[131] Atta-ur-Rahman and S Ahmad ldquoA furanoid diterpene 10120572-hydroxycolumbin from Tinospora malabaricardquo Phytochem-istry vol 27 no 6 pp 1882ndash1884 1988

[132] N-B Qin A-L Wang D-H Li et al ldquoCytotoxic clerodanefuranoditerpenoids from the root of Tinospora sagittatardquo Phy-tochemistry Letters vol 12 pp 173ndash176 2015

[133] H B Li J Hu J C Chen and M H Qiu ldquoChemicalconstituents of Tinospora cravenianardquoNatural Product Researchand Development vol 17 no 2 pp 125ndash127 2005

[134] N Fukuda M Yonemitsu T Kimura S Hachiyama K Miya-hara and T Kawasaki ldquoStudies on the constituents of the stemsof Tinospora tubereulata BEUMEE II1) new diterpenoidsborapetoside A and borapetol Ardquo Chemical amp PharmaceuticalBulletin vol 33 no 10 pp 4438ndash4444 1985

[135] U Sharma M Bala R Saini et al ldquoPolysaccharide enrichedimmunomodulatory fractions fromTinospora cordifolia (Willd)miers ax hook F amp Thomsrdquo Indian Journal of ExperimentalBiology vol 50 no 9 pp 612ndash617 2012

[136] R Maurya and S S Handa ldquoTinocordifolin a sesquiterpenefrom Tinospora cordifoliardquo Phytochemistry vol 49 no 5 pp1343ndash1345 1998

[137] N G Bisset and J Nwaiwu ldquoQuaternary alkaloids of Tinosporaspeciesrdquo Planta Medica vol 48 no 4 pp 275ndash279 1983

[138] H M Chang A M El-Fishawy D J Slatkin and P L Schiff JrldquoQuaternary alkaloids of Tinospora capillipesrdquo Planta Medicavol 50 no 1 pp 88ndash90 1984

[139] Y F Zhang Q R Shi P Y Shi W D Zhang and Y Y ChengldquoCharacterization of isoquinoline alkaloids diterpenoids andsteroids in the Chinese herb Jin-Guo-Lan (Tinospora sagittataand Tinospora capillipes) by high-performance liquid chro-matographyelectrospray ionization with multistage mass spec-trometryrdquoRapid Communications inMass Spectrometry vol 20no 15 pp 2328ndash2342 2006

[140] RMaurya P Gupta K Chand et al ldquoConstituents ofTinosporasinensis and their antileishmanial activity against Leishmaniadonovanirdquo Natural Product Research vol 23 no 12 pp 1134ndash1143 2009

[141] Y Y Guo L B Lin XW Fu K Keisuke and O Yukio ldquoStudieson alkaloids from Tinospora hainanesisrdquo Journal of HainanMedical College vol 10 no 5 pp 293ndash297 2004

[142] S PramanM J Mulvany D EWilliams R J Andersen and CJansakul ldquoHypotensive and cardio-chronotropic constituents ofTinospora crispa andmechanisms of action on the cardiovascu-lar system in anesthetized ratsrdquo Journal of Ethnopharmacologyvol 140 no 1 pp 166ndash178 2012

[143] R A Barraco D R Marcantonio J W Phillis and W RCampbell ldquoThe effects of parenteral injections of adenosine andits analogs on blood pressure and heart rate in the ratrdquo GeneralPharmacology vol 18 no 4 pp 405ndash416 1987

[144] F Samita C O Ochieng P O Owuor and L A O ManguroldquoNew ceramide from the aerial part of Tinospora oblongifoliawith cytotoxic activitiesrdquo Natural Product Research vol 28 no9 pp 661ndash666 2014

[145] P Pushp N Sharma G S Joseph and R P Singh ldquoAntioxidantactivity and detection of (minus)epicatechin in the methanolicextract of stem of Tinospora cordifoliardquo Journal of Food Scienceand Technology vol 50 no 3 pp 567ndash572 2013

[146] C-C Chang S L Ho and S-S Lee ldquoAcylated glucosylflavonesas 120572-glucosidase inhibitors from Tinospora crispa leafrdquo Bioor-ganic and Medicinal Chemistry vol 23 no 13 pp 3388ndash33962015

[147] P Tuntiwachwuttikul N Boonrasri J B Bremner and WC Taylor ldquoRearranged clerodane diterpenes from Tinosporabaenzigerirdquo Phytochemistry vol 52 no 7 pp 1335ndash1340 1999

[148] Y Y Guo K Kojima L B Lin et al ldquoA new N-methyltetrahy-droprotoberberine alkaloid from Tinospora hainanensisrdquoChemical and Pharmaceutical Bulletin vol 47 no 2 pp287ndash289 1999

[149] T Yokozawa T SWang C P Chen andMHattori ldquoInhibitionof nitric oxide release by an aqueous extract of Tinosporatuberculatardquo Phytotherapy Research vol 14 no 1 pp 51ndash532000

[150] T Yokozawa T Tanaka and T Kimura ldquoExamination of thenitric oxide production-suppressing component in Tinosporatuberculatardquo Biological and Pharmaceutical Bulletin vol 24 no10 pp 1153ndash1156 2001

[151] M Jahfar ldquoGlycosyl composition of polysaccharide from Tin-ospora cordifoliardquo Acta Pharmaceutica vol 53 no 1 pp 65ndash692003

[152] U Sharma P Bhandari N Kumar and B Singh ldquoSimultaneousdetermination of ten sugars inTinospora cordifolia by ultrasonicassisted extraction and LC-ELSDrdquoChromatographia vol 71 no7-8 pp 633ndash638 2010

[153] M Jahfar andPAzadi ldquoGlycosyl composition of polysaccharidefrom Tinospora cordifolia II glycosyl linkagesrdquo Acta Pharma-ceutica vol 54 no 1 pp 73ndash78 2004

[154] P V Leyon and G Kuttan ldquoInhibitory effect of a polysaccharidefrom Tinospora cordifolia on experimental metastasisrdquo Journalof Ethnopharmacology vol 90 no 2-3 pp 233ndash237 2004

[155] Q R Shi M J Liang W D Zhang et al ldquoQuantitativeLCMSMS method and pharmacokinetic studies of columbinan anti-inflammation furanoditerpen isolated from radixTinosporaerdquoBiomedical Chromatography vol 21 no 6 pp 642ndash648 2007

[156] S Gandhi M M Devi S Pal R P Tripathi and S KhushuldquoMetabolic regulatory variations in rats due to acute cold stressamp Tinospora cordifolia intervention high resolution 1H NMRapproachrdquoMetabolomics vol 8 no 3 pp 444ndash453 2012

[157] N N Rege U M Thatte and S A Dahanukar ldquoAdaptogenicproperties of six rasayana herbs used in Ayurvedic medicinerdquoPhytotherapy Research vol 13 no 4 pp 275ndash291 1999

[158] A Agarwal S Malini K L Bairy and M S Rao ldquoEffect ofTinospora cordifolia on learning and memory in normal andmemory deficit ratsrdquo Indian Journal of Pharmacology vol 34no 5 pp 339ndash349 2002

[159] P N Manjrekar C I Jolly and S Narayanan ldquoComparativestudies of the immunomodulatory activity of Tinospora cordi-folia and Tinospora sinensisrdquo Fitoterapia vol 71 no 3 pp 254ndash257 2000

[160] C V Chandrasekaran L N Mathuram P Daivasigamani andU Bhatnagar ldquoTinospora cordifolia a safety evaluationrdquoToxicol-ogy in Vitro vol 23 no 7 pp 1220ndash1226 2009

[161] Y R Karkal and L K Bairy ldquoSafety of aqueous extractof Tinospora cordifolia (Tc) in healthy volunteers a double

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

32 Evidence-Based Complementary and Alternative Medicine

blind randomised placebo controlled studyrdquo Iranian Journal ofPharmacology andTherapeutics vol 6 no 1 pp 59ndash61 2007

[162] S S Nayampalli S S Ainapure B D Samant R G KudtarkarN K Desai and K C Gupta ldquoA comparative study of diureticeffects of Tinospora cordifolia and hydrochlorothiazide in ratsand a preliminary phase I study in human volunteersrdquo Journalof Postgraduate Medicine vol 34 no 4 pp 233ndash236 1988

[163] A K Upadhyay K Kumar A Kumar and H S MishraldquoTinospora cordifolia (Willd) Hook f andThoms (Guduchi)mdashvalidation of the Ayurvedic pharmacology through experi-mental and clinical studiesrdquo International Journal of AyurvedaResearch vol 1 no 2 pp 112ndash121 2010

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom