artocarpus: a review of its traditional uses, phytochemistry and … · 2014-08-13 · journal of...

R

A

UD

a

ARRAA

KAAACJ

C

EGiMmhS

0d

Journal of Ethnopharmacology 129 (2010) 142–166

Contents lists available at ScienceDirect

Journal of Ethnopharmacology

journa l homepage: www.e lsev ier .com/ locate / je thpharm

eview

rtocarpus: A review of its traditional uses, phytochemistry and pharmacology

.B. Jagtap, V.A. Bapat ∗

epartment of Biotechnology, Shivaji University, Vidyanagar, Kolhapur 416 004, (MS), India

r t i c l e i n f o

rticle history:eceived 23 October 2009eceived in revised form 19 March 2010ccepted 21 March 2010vailable online 7 April 2010

eywords:rtocarpusntidiabeticnti-inflammatoryytotoxicity

acalin

a b s t r a c t

The genus Artocarpus (Moraceae) comprises about 50 species of evergreen and deciduous trees. Eco-nomically, the genus is of appreciable importance as a source of edible fruit, yield fairly good timberand is widely used in folk medicines. The aim of the present review is to present comprehensive infor-mation of the chemical constituents, biological and pharmacological research on Artocarpus which willbe presented and critically evaluated. The close connection between traditional and modern sources forethnopharmacological uses of Artocarpus species, especially for treatment against inflammation, malarialfever, diarrhoea, diabetes and tapeworm infection. Artocarpus species are rich in phenolic compoundsincluding flavonoids, stilbenoids, arylbenzofurons and Jacalin, a lectin. The extracts and metabolites ofArtocarpus particularly those from leaves, bark, stem and fruit possess several useful bioactive compoundsand recently additional data are available on exploitation of these compounds in the various biologicalactivities including antibacterial, antitubercular, antiviral, antifungal, antiplatelet, antiarthritic, tyrosi-
nase inhibitory and cytotoxicity. Several pharmacological studies of the natural products from Artocarpushave conclusively established their mode of action in treatment of various diseases and other health ben-efits. Jacalin, a lectin present in seeds of this plant has a wide range of activities. Strong interdisciplinaryprogrammes that incorporate conventional and new technologies will be critical for the future develop-ment of Artocarpus as a promising source of medicinal products. In the present review, attempts on the important findings have been made on identification; synthesis and bioactivity of metabolites present inArtocarpus which have been highlighted along with the current trends in research on Artocarpus.
© 2010 Elsevier Ireland Ltd. All rights reserved.

ontents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1431.1. General botanical description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1431.2. Use in traditional medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

2. Phytochemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1452.1. Fruits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1452.2. Seeds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

3. Biological activities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1463.1. Antibacterial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1463.2. Antimalarial effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
3.3. Antitubercular activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.4. Antiviral activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.5. Cytotoxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3.6. Antiplatelet effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Abbreviations: ACV, acyclovir; AEAC, l-ascorbic acid-equivalent antioxidant capacity; BD, effective dose; ELISA, enzyme-linked immunosorbent assay; FACS, fluorescence-activaC–MS, gas chromatography–mass spectrometry; GCK, glucokinase; HIV, human imm

nducible nitric oxide synthase; KB, human oral epidermoid carcinoma; LPS-IFN, lipopolysaIC, minimum inhibitory concentration; MPLC, medium pressure liquid chromatographyagnetic resonance; OxLDL, oxidized low-density lipoprotein; PAA, phosphonoacetic acid

uman platelet rich plasma; RA, rheumatoid arthritis; RE, retinol equivalents; ROS, reactiEM, scanning electron microscope; STZ, streptozotocin; TK, thymidine kinase; TUNEL, te∗ Corresponding author. Tel.: +91 231 2609365/2609155; fax: +91 231 291533.

E-mail address: [email protected] (V.A. Bapat).

378-8741/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.jep.2010.03.031

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

C, human breast cancer; CIA, collagen induced arthritis; EC, effective concentration;ted cell sorter; FRAP, ferric-reducing antioxidant power; GC, gas chromatography;

unodeficiency virus; HSV, herpes simplex virus; HSK, hepatic hexokinase; iNOS,ccharide-interferon; LC, lethal concentration; MABA, microplate Alamar Blue assay;; MPO, myeloperoxidase; MTT, microculture tetrazolium technique; NMR, nuclear; PARP, poly(ADP-ribose) polymerase; PMNs, polymorphonuclear neutrophils; PRP,ve oxygen species; RP-HPLC, reverse phase high-pressure liquid chromatography;rminal deoxynucleotidyl transferase nick end labeling.

http://www.sciencedirect.com/science/journal/03788741

http://www.elsevier.com/locate/jethpharm

mailto:[email protected]

dx.doi.org/10.1016/j.jep.2010.03.031

U.B. Jagtap, V.A. Bapat / Journal of Ethnopharmacology 129 (2010) 142–166 143

3.7. Antifungal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1493.8. Antirotavirus/antidiarrhoeal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1493.9. Antidiabetic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1503.10. Anti-inflammatory activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1503.11. Inhibitors of tyrosinase activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1503.12. Inhibitors of 5-lipoxygenase activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1513.13. Inhibitors of 5-� reductase activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1513.14. Antiarthritic effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1513.15. Antiatherosclerotic activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523.16. Anthelmintic effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523.17. Antioxidant activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1523.18. Corneal epithelial wound healing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

4. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154Appendix A. Constituents of Artocarpus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

. . . . . .

1

iAtoapmrnafeaTna((1

adTpTAapoatAebptmopfms

io

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. Introduction

Consumption of plant derived medicines is wide spread andncreasing significantly in both traditional and modern medicine.ccording to The World Health Organization, more than 80% of

he world population in developing countries depends primarilyn plant based medicines for basic healthcare needs (Canter etl., 2005). A few of these genera viz. Morus, Ficus, and Artocar-us are economic sources of food and widely used in traditionaledicine, agriculture and industry (Jarret, 1959). These genera

eceived a great level of scientific interest as they contain medici-ally important secondary metabolites possessing useful biologicalctivities. A number of Artocarpus species are used as food andor traditional folk medicines in South-East Asia, Indonesia, West-rn part of Java and India. Artocarpus plants offer advantages asprofitable multipurpose crop for producing fruits and timber.

he exceptional medicinal value of Artocarpus has long been recog-ized and economically the genus is of appreciable importance assource of edible aggregate fruit; such as Artocarpus heterophyllus

jackfruit), Artocarpus altilis (breadfruit) and Artocarpus chempedenChempedak) and yielding fairly good timber (Verheij and Coronel,992).

Extracts of the aerial and underground plant parts have beenpplied in traditional medicine for the treatment of diarrhoea,iabetes, malarial fever, tapeworm infection and other ailments.he other uses include wound healing, antisyphilic, expectorantroperties and also use to treat anemia, asthma and dermatitis.his comprehensive review provides a botanical description ofrtocarpus species and their phytochemical constituents in theerial and underground parts. In addition, in vitro and in vivoharmacological studies are reviewed and discussed, focusingn antibacterial, antitubercular, antiviral, cytotoxic, antidiarrheal,ntiarthritic, antihelmintic, anti-inflammatory, antioxidative andyrosinase, 5-lipoxygenase, 5-� reductase inhibitory activities ofrtocarpus species. Most of the pharmacological effects can bexplained by the phenolic compounds including flavonoids, stil-enoids, arylbenzofurons (Hakim et al., 2006) present in all plantarts and Jacalin, a lectin (Kabir, 1998) present in seeds of cer-ain Artocarpus species. However, future efforts should concentrate

ore on in vitro and in vivo studies and also on clinical trials inrder to confirm traditional knowledge in the light of a rationalhytotherapy. Especially the efficacy of Jacalin, a lectin extractedrom the seeds of Artocarpus in controlling viral infections, HIV and

odulation of immune response to pathogens (Favero et al., 1993)hould be further substantiated in clinical studies.

The present review assesses the potential of Artocarpus spp.n relation to its traditional uses and in terms of findings basedn modern bioscientific research. The link between conventional

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164

remedies and recent research in various areas has been well estab-lished in other plants (Das et al., 2007; Gutierrez et al., 2008;Lansky et al., 2008) which facilitate to determine effective modeof action of plant derived products. The present plant is known tocontain several pharmacological important biomolecules as listedearlier whose efficacy is well established by several biochemicaland pharmacological studies. This review indents to compile vari-ous studies on this plant and critically evaluates the issues relatedto the ethnobotanical, ethnomedical and ethnopharmacology ofArtocarpus.

1.1. General botanical description

As a group among forest tree plants, Artocarpus species areknown to occupy a variety of ecological niches across differenthabitats and are being diverse and numerous in various forestecosystems. The diversity, conservation status and state of knowl-edge of Artocarpus (Moraceae) are not uniform worldwide. Thefamily consists of 60 genera comprising 1400 species distributed inthe tropical and subtropical regions of Asia. The genus ArtocarpusJ.R. & G. Foster (Moraceae) comprises mainly of breadfruit and jack-fruit trees. It is a native of South and South-East Asia, New Guineaand the Southern Pacific having 50 species. These are restrictedto evergreen forests in the humid tropical zone and usually foundbelow an altitude of 1000 m. Artocarpus species are evergreen ordeciduous small to large monoecious trees; with all parts containwhite latex. Leaves are spirally arranged or alternate and distichous,simple and are entire to pinnatifid or pinnate, coriaceous, glabrousto pubescent. Inflorescence is unisexual, capitate, head cylindric toglobose, solitary or paired in leaf axils or rami or cauliflorous, flow-ers numerous and are densely packed together, embedded in thereceptacle, the perianth enclosing a single ovary or stamen, usuallymixed with abundant stalked inter floral bracts; male head withperianths tubular and bi lobed or perforate above to 2-4-partite,stamens short to long exerted; female heads with perianths tubu-lar thin walled below and enclosing ovary, thick walled above witha narrow lumen containing the style; perianths persisting and par-tially or completely fixed with one another to form syncarp, ovaryunilocular, style apical to lateral, simple or bifid. Aggregate fruit(Syncarp) formed by the enlargement of the entire female head.Seeds are large without endosperm, germination hypogeal (Verheijand Coronel, 1992). The common names, uses and geographicaldistribution of Artocarpus species are presented in Table 1.

1.2. Use in traditional medicine

Many members of the genus Artocarpus have also been usedas traditional folk medicine in South-East Asia for the treatment

144 U.B. Jagtap, V.A. Bapat / Journal of Ethnopharmacology 129 (2010) 142–166

Table 1Common names, uses and geographical distribution of some Artocarpus species.

Synonyms Common names Uses Origin and geographicaldistribution

1. Artocarpus altilis(Parkinson) Fosberg

Artocarpus camansi BlancoArtocarpus communis J.R. & G.Forst.Artocarpus incisaArtocarpus incisus (Thunb.) L.f.

Breadfruit Fruit pulp tonic for liver, leavesto treat liver cirrhosis,hypertension and diabetes.

Native to Pacific and Tropical Asia,Indonesia, Papua New Guinea

2. Artocarpus chamaBuch.-Ham.

Artocarpus chaplasha Roxb.Artocarpus melinoxylus Gagnep

Chaplasha – India, Burma

3. Artocarpus chempedenSpreng.

– Chempedak Seeds in diarrhea, roots inmalaria fever.

South-East Asia, Indonesia

4. Artocarpus elasticusReinw. Ex Blume

– – Bark in inflammation andfemale contraception, latex indysentery, leaves to treattuberculosis.

South-East Asia, West Malaysia

5. Artocarpus gomezianusWall. Ex Trecul.

Artocarpus pomiformis Teijsm &Binn

Tampang burung – Western part of Indonesia

6. Artocarpus heterophyllusLam.

Artocarpus brasiliensis GomezArtocarpus integraArtocarpus integrifolia auct.Artocarpus jaca Lam.Artocarpus maxima BlancoArtocarpus philippensis Lamk

Jackfruit Fruits edible, roots in diarrheaand fever, leaves as antisyphilicand vermifuge, ulcers andwound healing, leaves andstem barks used to treatanemia, asthma, dermatitis,diarrhoea, cough.

Native to Western Ghats India.Introduced in South-East Asianregion

7. Artocarpus hirsutus Lam. Artocarpus hirsuta Lam. – – South India

8. A integer (Thunb.) Merr. Artocarpus champeden (Lour.)StokesArtocarpus integrifolius L.f.Artocarpus polyphema PersoonPolyphema champeden Lour.Radermachia integra Thunb.

– Fruits edible. Burma, Peninsular Thialand,Peninsular Malaysia, Sumatra,Borneo, Sulawesi lingga,Archipelago

9. Artocarpus lacuchaBuch.-Ham.

Artocarpus lakoocha Roxb. Monkeyjack,Lakoocha

Bark chewed like betel nutused to treat skin ailments.

Native to humid sub. HimalayanRegions of India, South China,South-East Asia

10. Artocarpus lowii King – Miku Sap used as an ointment and ascooking oil.

Rare species in Malaysia

11. Artocarpus nobilis Thw. – – Seeds and young fruits edible. Endemic to Sri Lanka

12. Artocarpus – Marang, Terap Fruits edible. Borneo, Philippines

oajrswoabcsdsTihNrtmrhbd

i

odoratissimus Blanco.13. Artocarpus rotunda

(Hout) Panzer– –

f inflammation, malarial fever and to treat the ulcers, abscessnd diarrhea (Perry, 1980; Heyne, 1987). The pulp and seeds ofackfruit are used as a cooling tonic and pectorial, roots in diar-hea and fever, leaves to activate milk in women and animals, as aource to treat antisyphilic and vermifuge, leaf ash applied to ulcersounds and the warmed leaves have healing properties if pasted

n the wounds. The latex mixed with vinegar promotes healing ofbscesses, snakebite and glandular swellings. The leaves and stemarks have been used to treat anemia, asthma, dermatitis, diarrhea,ough and as an expectorant (Balbach and Boarim, 1992). The fruits,eeds and trunk wood contained chemical compounds with aphro-isiac properties (Le Cointe, 1947; Ferrao, 1999). The wood has aedative effect in convulsions and its pith is said to cause abortion.he root is used as a remedy against skin diseases and asthma andts extract is used to reduce fever and diarrhea (ICUC, 2003). Theeartwood of Artocarpus heterophyllus is used by monks in ruralortheastern Thailand’s Forest Tradition monasteries to dye their

obes. Chips of wood are boiled in water, producing a rich earth-one dye called “gaen-kanun,” which is held to have remarkable

edicinal qualities. In fact, monks of this tradition never wash theirobes. Once a week, the robes are re-boiled in jackfruit dye, and are
ung to dry in the sun. Robes treated in this manner never emitsad odor and provides protection from fungal infections and skinisorders (Salguero, 2003).
Artocarpus altilis (Parkinson) Fosberg, a tree of moderate size,s widely cultivated in tropics for a staple crop, for construction

– South-East Asia, Indonesia

material and as an animal feed, and its leaves have been used tra-ditionally for the treatment of liver cirrhosis, hypertension anddiabetes (Wang et al., 2006). The lakocha fruits are generally eatenfresh. The edible fruit pulp is believed to acts as a tonic for theliver. The raw fruits and male flowers spikes (acidic and astrin-gent) are utilized in pickles and chutney. The brown powder calledPuag-Haad in Thailand is a product of the aqueous extraction ofArtocarpus lakoocha Roxb. prepared by boiling the wood chips andthen evaporating water away. This preparation has been used asa traditional anthelmintic drug for treatment of tapeworm infec-tion in Thailand (Charoenlarp et al., 1981; Salguero, 2003). Thehardwood sold as lakuch is comparable to famous teak wood, isused for constructions, furniture, boat making and cabinet work.Tree bark containing 8.5% tannin is chewed like betel nuts and isalso used to treat skin ailments. It yields a durable fiber good forcordage. The wood and roots yield a lavish color dye (Joshee etal., 2002). The sap from Artocarpus lowii is traditionally used as anointment and as cooking oil by old folk medicine (Jamil et al., 2008).Artocarpus chempeden is one of the Indonesian folk medicines; theseeds have been used against diarrhea and its roots against malariafever (Heyne, 1987). In the western part of Java, Artocarpus elasti-
cus Reinw. ex Blume has been used to treat inflammation, femalecontraception (bark), dysentery (latex) and young leaves for treattuberculosis (Heyne, 1987). Besides the medicinal uses, Artocar-pus species is employed as a food and in construction of houses(Table 2).


Table 2Commercial uses of Artocarpus species.

Plant part Use Reference

Fruit Artocarpus altilis (breadfruit)Artocarpus heterophyllus (jackfruit)Artocarpus integer (Chempedak)

Food: vegetable, pickled, canned chutney, honey, jam, jelly, paste,candies, concentrate and powder, confectionery, etc.

ICUCVerheij and Coronel (1992)

Seed Seeds can be eaten boiled, roasted or dried and salted as table nuts,flour for baking, canning in brine, tomato sauce.

ICUCVerheij and Coronel (1992)

Seed powder as a substrate in solid-state fermentation for theproduction of Monascus pigments.

Babitha et al. (2007)

Wood In making furniture, oars, implements and musical instruments, usedin building construction and boat, a yellow dye to dye cotton, silk.

ICUCRujinirum et al. (2005)

Leaves Fodder to cattle and other livestock, leaf powder as an adsorbent forthe Removal of methylene blue from aqueous solution.

Uddin et al. (2009)

Latex Used in varnishes, glue for mending chinaware and pottery, caulkingfor boats and buckets.

e fram

oval o

2

flse

2

rDds(fiopmv1pmrmdlva

oiibrws(awtavit

Roots Carving and pictur

Jackfruit peel Adsorbent for rem

. Phytochemistry

The Artocarpus species are rich in phenolic compounds includingavonoids, stilbenoids and arylbenzofurons. The chemical con-tituents of Artocarpus species have earlier been reviewed (Hakimt al., 2006).

.1. Fruits

The jackfruit is a high yielding fruit crop which bears fruits allound the year with peak production during the months of June andecember (Othman and Subhadrabandhu, 1995). It substitutes theiet of people both as vegetable and as a nutritious food during theeason, hence, considered as a poor man’s food in South-East AsiaSingh et al., 1963; Bose, 1985). Botanically, jackfruit is a compoundruit and consists primarily of three regions viz. the fruit axis (ined-ble region), the persistent perianth and the proper fruit. The 100 gf ripe edible portion of jackfruit contains carbohydrate (18.9 g),rotein (1.9 g), fat (0.1 g), moisture (77%), fiber (1.1 g), total mineralatter (0.8 g), calcium (20 mg), phosphorus (30 mg), iron (500 mg),

itamin A (540 IU), thiamin (30 mg), having caloric value 84 (Bose,985). The distribution of free sugars and fatty acids of differentarts of jackfruit were identified and quantified by gas–liquid chro-atography as their trimethylsilyl derivatives and methyl esters,

espectively. Fructose, glucose and sucrose were found to be theajor sugars in all parts of jackfruit, except in the bark, which is

evoid of glucose. Capric, myristic, lauric, palmitic, oleic, stearic,inoleic and arachidic acids were found as major fatty acids witharying proportions in different parts of jackfruit (Chowdhury etl., 1997).

The chemical composition and flavor changes during ripeningf jackfruit cultivar: J3 were evaluated. Significant changes in acid-ty and color was obtained, but no significant changes were foundn moisture and crude fiber contents during ripening. Total solu-le solids and total sugars increased significantly throughout theipening process. Total soluble solids at the top portion of the fruitere significantly higher than middle and bottom portions of the

ame fruit. A high content of malic acid was found in unripe fruitday 1). In contrast, ripened fruit (days 5 and 6) contained a highmount of citric acid. Overall, the total amount of organic acidsas found to decrease from the early to later stage of ripening. A

otal of 23 volatile compounds were tentatively identified by GCnd GC–MS (Ong et al., 2006). The aroma volatiles from two fruitarieties of jackfruit viz. hard jackfruit and soft jackfruit growingn the Amazon were studied. The major components identified inhe aroma concentrate of “hard jackfruit” variety were isopentyl

ing.

f Cd(II) from aqueous solution. Inbaraj and Sulochana(2004)

isovalerate (28.4%) and butyl isovalerate (25.6%). The aroma con-centrate of “soft jackfruit” was dominated by isopentyl isovalerate(18.3%), butyl acetate (16.5%), ethyl isovalerate (14.4%), butyl iso-valerate (12.9%) and 2-methylbutyl acetate (12.0%). These resultswere compatible with morphological variation and their distin-guished aromas of the fruits (Maia et al., 2004).

Chandrika et al. (2005) have studied the analysis of carotenoidscomposition of jackfruit (Artocarpus heterophyllus sinhala: Waraka)kernel using medium pressure liquid chromatography (MPLC)and visible spectrophotometer and determined the bioavailabil-ity and bioconversion of carotenoids present in jackfruit kernelby monitoring the growth, levels of retinol and carotenoids inthe liver and serum of Wistar rats provided with jackfruit pulpincorporated into a standard daily diet. Carotenoids pigmentswere extracted using petroleum ether/methanol and saponifiedusing 10% methanolic potassium hydroxide. Six carotenoids weredetected in jackfruit kernel. The carotenes �-carotene, �-carotene,�-zeacarotene, �-zeacarotene and �-carotene-5,6-epoxide and adicarboxylic carotenoid, crocetin, were identified, correspondingtheoretically to 141.6 retinol equivalents (RE) per 100 g. The jack-fruit is a good source of pro vitamin A carotenoids, though notas good as papaya. Serum retinol concentrations in rats sup-plemented with jackfruit carotenoids were significantly higher(p = 0.008) compared with the control group. The same was true forliver retinol (p = 0.006). Quantification was carried out by RP-HPLC.These results showed that the biological conversion of pro vitaminA, in jackfruit kernel appeared satisfactory. Thus increased con-sumption of ripe jackfruit could be advocated as part of a strategy toprevent and control vitamin Artocarpus The main carotenoids foundin jackfruit were all-trans-lutein (24–44%), all-trans-�-carotene(24–30%), all-trans-neoxanthin (4–19%), 9-cis-neoxanthin (4–9%)and 9-cis-violaxanthin (4–10%). The carotenoids composition ofjackfruit was successfully determined and 14 of the 18 carotenoidswere reported for the first time. Differences among batches mightbe due to the genetic and/or agricultural factors (Faria et al., 2009).The phenolic constituents from the fruits of Artocarpus nobilis andtheir antioxidant activity against DPPH radical have been studied(Jayasinghe et al., 2006).

2.2. Seeds

The occurrence of lectin, termed as Jacalin, in the seeds ofjackfruit was reported for first time by Chatterjee et al. (1979).The Jacalin is tetrameric two-chain lectin molecular mass 65 KDacombining a heavy �-chain of 133 amino acid residues with alight �-chain of 20–21 amino acid residues (Young et al., 1991).

1 thnop

T(C(1ntys(sejeMnloDticptnigtt

atchwppsbi1tTanimpflr(

3

3

scptBsS

46 U.B. Jagtap, V.A. Bapat / Journal of E

he Jacalin has been reported to bind specifically to human IgAChatterjee et al., 1979; Pereira et al., 1980; Bunn-Moreno andampos-Neto, 1981; Saxon et al., 1987), d-galactose and T-antigenThomsen-Friedenreich antigen, Gal �1–3GalNAc) (Sastry et al.,986), which is expressed in more than 85% of human carci-omas (Sankarnarayanan et al., 1996). Jacalin is synthesized onhe rough endoplasmic reticulum. The immunocytological anal-sis of jackfruit cotyledons revealed that Jacalin accumulates inmall punctuates structures distributed throughout the cytoplasmPeumans et al., 2000). The Jacalin is a single major protein repre-enting more than 50% of the proteins of the jackfruit crude seedxtract (Kabir et al., 1993). The subsequent studies revealed thatackfruit seed extract possesses a potent and selective mitogenicffect on T-cell proliferation and B-cell polyclonal activation (Deiranda-Santos et al., 1991). This novel second lectin was first

amed as artocarpin but this term used to designate an Artocarpusakoocha lectin (Chowdhury et al., 1991). This led to propose KM+r artocarpin which is specific to mannose and D-glucose but not-galactose (Santos-de-Olievira et al., 1994). A reinvestigation of

he KM+/artocarpin carbohydrate binding properties revealed thatt is a polyspecific lectin that reacts with wide range of monosac-harides (Barre et al., 2004). The artocarpin is made up of a singleolypeptide chain of 159 amino acids sharing 52% identity withhe Jacalin sequences. Jacalin is a glycosylated while artocarpin isot (Rosa et al., 1999). Therefore, Jacalin has a potential value in

mmunobiological research including isolation of human plasmalycoproteins (IgA1, C1-inhibitor, hemopexin, �-2hsg), investiga-ion of IgA nephropathy, the analysis of O-linked glycoproteins andhe detection of the tumors (Kabir, 1998) (Table 3).

A comparative study of Artocarpus heterophyllus and Treculiafricana seeds, both of Moraceae family, was carried out to establishheir chemical compositions and evaluate their mineral elementontent in order to investigate the possibility of using them foruman and or animal consumption and also to examine if thereas a relationship between the properties of these seeds. Artocar-

us heterophyllus and Treculia africana are rich in protein and theirrotein contents are higher than those from high protein animalources such as beef and marine fishes. Both seeds have high car-ohydrate content and could act as a source of energy for animals if

ncluded in their diets. The oil contents of the seeds are 11.39% and8.54% for Artocarpus heterophyllus and Treculia africana, respec-ively. The oils are consistently liquid at the room temperature.he results of the physicochemical properties of the two seedsre comparable to those of conventional oilseeds such as ground-ut and palm kernel oils and could be useful for nutritional and

ndustrial purposes. The seeds were found to be good sources ofineral elements. The result revealed that potassium to be the

revalent mineral elements which are 2470.00 and 1680.00 ppmor Artocarpus heterophyllus and Treculia africana, respectively fol-owed by sodium, magnesium and calcium. They also containeasonable quantity of iron, particularly in Artocarpus heterophyllus148.50 ppm) (Ajayi, 2008).

. Biological activities

.1. Antibacterial activity

The crude methanolic extracts of the stem and root barks,tem and root heart wood, leaves, fruits and seeds of Arto-arpus heterophyllus and their subsequent partitioning with
etrol, dichloromethane, ethyl acetate and butanol gave frac-ions that exhibited a broad spectrum antibacterial activity againstacillus cereus, Bacillus coagulans, Bacillus megaterium, Bacillusubtilis, Lactobacillus casei, Micrococcus luteus, Micrococcus roseus,taphylococcus albus, Staphylococcus aurens, Staphylococcus epider-
harmacology 129 (2010) 142–166

midis, Streptococcus faecalis, Streptococcus pneumoniae, Agrobac-terium tumaefaciens, Citrobacter freundii, Enterobacter aerogenes,Escherichia coli, Klebsiella pneumonia, Neisseria gonorrhoeae, Pro-teus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonellatyphi, Salmonella typhimurium, Serratia marcescens, Trichomonasvaginalis. The butanol fractions (concentration 4 mg/disc) of rootbark and fruits of Artocarpus heterophyllus were found to be moreactive and have been examined by disc diffusion methods (Khanet al., 2003). The methanolic plant extract consists of two activeisoprenyl flavones artocarpin and artocarpesin were isolated fromArtocarpus heterophyllus. These inhibited the growth of primarycariogenic bacteria at concentration of 3.13–12.5 �g/ml and alsoexhibited the growth inhibitory effects on plaque-forming Strep-tococci. This finding showed that phytochemicals from Artocarpusheterophyllus would be potent compounds for the prevention ofdental caries (Sato et al., 1996). The artonin E has been isolatedfrom the bark of Artocarpus rigida Blume The artonin E (concentra-tion 250 �g/disc) showed antimicrobial activity against Escherichiacoli and Bacillus subtilis produced clear zone with a diameter of 1.2and 0.9 cm, respectively, while the standard used the canamycinsulphate (concentration 240 �g/disc) produced clear zone with adiameter of 2.2 cm. Therefore this compound has possibility to beused as an antibiotic (Suhartati et al., 2008).

3.2. Antimalarial effects

The quantitative assessment of antimalarial activity in vitrowas determined by means of the microculture radioisotope tech-nique based on the method described by Desjardins et al. (1979);which was used to examine the antiplasmodial activities of crudeextracts of the aerial parts of Artocarpus integer. An in vitroantimalarial assay was carried out using a multi drug resistantstrain of the malarial parasite, Plasmodium falciparum K1. Thecrude extracts of aerial parts of Artocarpus integer showed mod-erate in vitro antimalarial activity against Plasmodium falciparumwith an EC50 of 6.8 �g/ml. Further, antimalarial activity studyof the aerial parts of Artocarpus integer led to the isolation ofthe prenylated stilbene, trans-4-(3-methyl-E-but-1-enyl)-3,5,2,4′-tetrahydroxystilbene with an EC50 of 1.7 �g/ml. The knownstilbenes, trans-4-isopentenyl-3,5,2′,4′-tetrahydroxystilbene (EC50of 8.2 �g/ml) and 4-methoxy-2,2-dimethyl-6-(2-(2-dihydroxy)phenyl-trans ethenyl) chromene (EC50 of 9.4 �g/ml) were alsoisolated. An EC50 value of 0.16 �g/ml was observed for the stan-dard sample, chloroquine diphosphate, in the same test system(Boonlaksiri et al., 2000).

The flavonoids 7-demethylartonol E, artonin F, cycloartobilox-anthone isolated from the root bark of Artocarpus rigidus Blumesubsp. rigidus exhibited in vitro antiplasmodial activity againstPlasmodium falciparum with an IC50 value 7.9, 2.4 and 3.7 �g/ml,respectively. The artemisinin (IC50 1 ng/ml) used as the standarddrug in the same test system (Namdaung et al., 2006).

In another report, Boonphong et al. (2007) showed antimalarialactivity of the roots of Artocarpus altilis which led to the isolation ofnine prenylated flavones. Out of which cycloartocarpin, artocarpinand chaplashin were isolated from the dichloromethane extract ofthe root and stems, whereas, morusin, cudraflavone B, cycloarto-biloxanthone, artonin E and artbiloxanthone were found in the rootbark exhibited moderate antiplasmodial activity with IC50 valuesranging from 1.9 to 4.3 �g/ml.

Widyawaruyanti et al. (2007) isolated two new prenylatedflavones artocapones A and B, along with seven known isopreny-
lated flavonoids artonin A, cycloheterophyllin, artoindonesianin E,artoindonesianin R, heterophyllin, heteroflavanone C and artoin-donesianin A-2 from the stem bark of Artocarpus champeden.These isolated compounds were tested for in vitro inhibitory activ-ity against Plasmodium falciparum 3D7. All compounds showed


Table 3Phytochemical and biochemical studies on lectins from Artocarpus species (Jacalin).

Lectin Species Focus of the phytochemical and biochemical studies Reference

Artocarpin (�-d-galactosyl-bindinglectin)

Artocarpus lakoocha (Artocarpus lacuchaBuch-Ham) (seeds)

Purification and characterization using affinitychromatography on a melibiose-agarose column.

Chowdhury et al.(1987)

Jacalin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Inhibits differentiation of human B cells by direct effectand activating T-suppressor cells.

Saxon et al. (1987)

Artocarpin Artocarpus lakoocha (Artocarpus lacuchaBuch-Ham) (seeds)

Characterization and purification using Rivanol. Chatterjee et al. (1988)


Isolation and characterization of Jacalin and study itsinteraction with human IgA1.

Hagiwara et al. (1988)

�-d-Galactose specificlectin

Artocarpus integra (Artocarpus heterophyllusLam.) (seeds)

Preliminary crystallographic study. Basu et al. (1988)

Anti-T lectin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Preparation and preliminary X-ray studies of two crystalforms of anti-T lectin.

Dhanaraj et al. (1988)


Developed simplified procedure for purification of C1inhibitor using Jacalin.

Pilatte et al. (1989)


Homology of the d-galactose specific lectins from Maclurapomifera and Artocarpus integrifolia.

Young et al. (1989)


Interaction of Ant-Egg glycoprotein with Jacalin. Ray and Chatterjee(1989)

Breadfruit lectin andJacalin

Artocarpus altilis (seeds)Artocarpus heterophyllus (seeds)

Structural and functional similarities between breadfruitLectin and Jacalin.

Pineau et al. (1990)

Jacalin Artocarpus heterophyllus (seeds) Mitogenic effect on human CD4 T-lymphocytes. Pineau et al. (1990)


Topography of the combining region of aThomsen-Friendenreich antigen specific lectin Jacalin.

Mahanta et al. (1990)


X-ray characterization of four New crystal forms of Jacalin. Banerjee et al. (1991)


Crude extracts contain two lectins with different biologicalactivities. Jacalin inhibits the proliferative activity ofhuman PMBC and murine spleen cells. While other lectinresponsible for mitogenic activities on human PMBC andmurine spleen cells.

De Miranda-Santos etal. (1991)

Jacalin and Artocarpin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Artocarpin is responsible for activation of T and B cells, andnot Jacalin.

De Miranda-Santos etal. (1991)

Artocarpin Artocarpus lakoocha (Artocarpus lacuchaBuch-Ham) (seeds)

Chemical modification studies of Artocarpin. Modificationof carboxyl groups arginine and lysine residues didnotaffect lectin activity. However modification of tryptophan,tyrosine and histidine residues led to a complete loss ofactivity.

Chowdhury et al.(1991)


Preliminary structure ofThomsen-friendenreich-antigen-specific lectin Jacalin.

Mahanta et al. (1992)

Jacalin Artocarpus heterophyllus (seeds) Structural and electron microscopic studies showed thatJacalin is 65 kDa tetramer.

Ruffet et al. (1992)

Jacalin Artocarpus heterophyllus (seeds) Identification of a novel 4-kDa Immunoglobulin-A bindingpeptide obtained by the limited proteolysis of Jacalin.

Kabir et al. (1993)

Jacalin Artocarpus heterophyllus (seeds) Isolation and characterization of Jacalin by isoelectricfocusing.

Kabir (1995)

Isolectins agglutinin(ALA)

Artocarpus lakoocha (Artocarpus lacuchaBuch-Ham) (seeds)

Two isolectins possessing two dissimilar subunits (� and�), bound non-covalently; and possess several similarproperties like blood type agglutination, pH and optimum,pH and temp. stability binding specificity towardsasialomucins.

Wongkham et al.(1995)

Mannose binding lectinnamed aschampedak-M

Artocarpus integer (seeds) Isolation and its interaction with human IgE and IgM. Lim et al. (1997)

Frutalin Artocarpus incisa L. (Artocarpus altilisParkinson) Fosberg. (seeds)

Isolation and partial characterization of lectin Moreira et al. (1998)

�-Galactoside bindinglectin

Artocarpus hirsuta (Artocarpus hirsutusLam.) (seeds)

Characterization of the sugar specificity and binding site.Hemagglutination activity on rabbit and humanerythrocytes (ABO).

Gurjar et al. (1998)

KM+/Artocarpin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Lectin binding properties of different Leishmania species. Andrade and Saraiva(1999)

Artocarpin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Crystal structure of Artocarpin. Pratap et al. (2002)

KM+ Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Protective effect of KM+ against Leishmania major infection. Panunto-Castelo et al.(2001)


Crystal structure of Jacalin-T-antigen complexes. Jeyaprakash et al.(2002)

Galactose bindinglectin

Artocarpus integra (Artocarpus heterophyllusLam.) (seeds)

Sequence of its subunit and interactions with humanserum O-glucosylated glycoproteins.

Rahman et al. (2002)


Studies saccharide binding affinity of recombinant singlechain Jacalin and normal folding like native Jacalin.

Sahasrabuddhe et al.(2004)


Table 3 (Continued )

Lectin Species Focus of the phytochemical and biochemical studies Reference

Artocarpin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)

Artocarpin is polyspecific lectin interacted with widerange of monosaccharides including galactose, mannose,N-acetylgalactosamine, glucose, sialic acid andN-acetylmuramic acid with preference for mannose.

Barre et al. (2004)


cDNA cloning and expression of KM+ in Escherichia coli andSaccharomyces cerevisiae.

Da Silva et al. (2005)


Induces neutrophil migration by haptotaxis. Pereira-da-Silva et al.(2006)

Lectin Artocarpus integrifolia (Artocarpusheterophyllus Lam.) (seeds)Artocarpus incisa (Artocarpus altilis

Structural characterization of novel chitin binding lectinJackin (from jackfruit) and frutackin (from breadfruit).

Trindade et al. (2006)

fect of31 (hlorect

iAio6sc

3

thd0eaecta(

tatbatr0eAt

3

iDiccdtTbpo

Parkinson) Fosberg. (seeds)Jacalin Artocarpus integrifolia (Artocarpus

heterophyllus Lam.) (seeds)EfA4co

nhibitory activity at 0.001–75.3 �mol/l concentration range.mong all these compounds, heteroflavone C had most potent

nhibitory activity with an IC50 value of 1 nmol/l less than thatf reported for a well-known antimalarial drug, chloroquine (IC50.3 nmol/l). The inhibitory activities of these prenylated flavonesupport its traditional use of the dried stem bark of Artocarpushampeden as an antimalarial drug.

.3. Antitubercular activity

The antitubercular activity performed against Mycobacteriumuberculosis H37Ra using the Microplate Alamar Blue Assay (MABA)as been described by Collin and Franzblau (1997). The standardrugs rifampicin, isoniazide and kanamycin showed MIC values.0023, 0.1 and 2.5 �g/ml, respectively, were employed as ref-rences. These all nine prenylated flavones, i.e. cycloartocarpin,rtocarpin, and chaplashin were isolated from the dichloromethanextract of the root and stems whereas morusin, cudraflavone B,ycloartobiloxanthone, artonin E, cudraflavone C and artobiloxan-hone were isolated from the roots of Artocarpus altilis exhibitedntitubercular activity with a minimum inhibitory concentrationMIC) ranging from 3.12 to 100 �g/ml (Boonphong et al., 2007).

The compounds flavonoid 7-demethylartonol E, artorigidusinogether with the four known phenolic compounds, the xanthonertonol B, the flavonoid artonin F, the flavonoid cycloartobiloxan-hone and the xanthone artoindonesianin C isolated from the rootark of Artocarpus rigidus sub sp. rigidus showed anti-mycobacterialctivity against Mycobacterium tuberculosis, with artonin F beinghe most active compound (MIC 6.25 �g/ml). The standard drugsifampicin, isoniazide and kanamycin sulfate showed MIC values.004, 0.06 and 2.5 �g/ml, respectively, were employed as refer-nces (Namdaung et al., 2006). Results supported the utilization ofrtocarpus elasticus young leaves in traditional medicine for treatuberculosis.

.4. Antiviral activity

Artocarpus lakoocha Roxburgh was investigated for its abil-ty to inhibit the growth of herpes simplex virus (HSV). It is aNA virus divided with two types HSV-1 and HSV-2. The HSV-1

s responsible for facial infections, visceral infections in immuneompromised hosts, and HSV encephalitis in adults. HSV-2 is asso-iated with infections of the genital tract and HSV-related neonataliseases (Jensen et al., 1977). The stilbene oxyresveratrol (2,4,3′,5′-
etrahydroxystilbene) was also studied for its anti-HIV activity.he stilbene oxyresveratrol possessed moderate activity againstoth types of HSV. In addition, oxyresveratrol was evaluated forotential anti-HIV activity against a wild-type human immun-deficiency virus type 1 (HIV-1/LAI) isolate and was found to
Jacalin on cell proliferation/cytotoxicity on theuman epidermoid carcinoma) and HT29 (humanal carcinoma).

Sahasrabuddhe et al.(2006)

be a modest inhibitor of HIV (EC50 28.2 mM), showing no toxi-city in PBM, CEM and Vero cells at 100 mM. The heartwood ofArtocarpus lakoocha, which contains a large amount of oxyresver-atrol, could be considered as a source of starting material for thedevelopment of a new natural product as anti-HSV and anti-HIVagents (Likhitwitayawuid et al., 2005). The methanolic extract ofheartwood of Artocarpus gomezianus was investigated for anti-herpetic principles and was showing 90% and 80% inhibition ata concentration of 100 �g/ml against HSV-1 and HSV-2, respec-tively. During the course of the separation, a new compound,artogomezianone was isolated, along with the known compoundscycloartocarpin, isocyclomorusin, artocarpin, norcycloartocarpin,norartocarpetin and oxyresveratrol. Evaluation of these isolatesfor inhibitory effects against herpes simplex virus (HSV) types 1and 2 was carried out using the inactivation method. The acyclovir(ACV) was used as positive control in the same test. Compoundscycloartocarpin, isocyclomorusin, norartocarpetin and oxyresver-atrol showed moderate activities against both types of HSV, whileartogomezianone, artocarpin and norcycloartocarpin were basi-cally inactive (Likhitwitayawuid et al., 2006).

Oxyresveratrol is a major compound purified from Artocarpuslakoocha, a Thai traditional medicinal plant, and was evaluatedfor its mechanism of action and therapeutic efficacy on cutaneousHSV infection in mice. For the inhibitory concentrations for 50%HSV-1 plaque formation of oxyresveratrol, three clinical isolates,thymidine kinase (TK)-deficient and phosphonoacetic acid (PAA)-resistant HSV-1 were 19.8, 23.3, 23.5, 24.8, 25.5 and 21.7 �g/mltested, respectively. Oxyresveratrol exhibited the inhibitory activ-ity at the early and late phase of viral replication and inhibitedthe viral replication with pretreatment in one-step growth assayof HSV-1 and HSV-2. Oxyresveratrol inhibited late protein synthe-sis at 30 �g/ml. The combination of oxyresveratrol and acyclovir(ACV) produced synergistic anti-HSV-1 effect, as characterized bythe isobologram of plaque inhibition. Mice orally treated withoxyresveratrol (500 mg/kg/dose) dose at 8 h before and three timesdaily had significant delay in herpetic skin lesion development(P < 0.05). Topical application of 30% oxyresveratrol ointment fivetimes daily significantly delayed the development of skin lesionsand protected mice from death (P < 0.0001) (Chuanasa et al., 2008).

3.5. Cytotoxicity

Suhartati et al. (2001) isolated a new prenylated flavone artoin-donesianin L along with four known phenolic compounds identified
as artonins M and E, cycloartobiloxanthone and artonin O fromroot bark of Artocarpus rotunda (Hout) Panzer. These compoundsshowed significant cytotoxicity against murine P388 leukemia cellswith an LC50 values 0.6, 7.9, 0.06, 4.6 and 0.9 �g/ml, respectively.The prenylated flavonoids, artonins E and O, artobiloxanthone

thnop

aAe2aisaad2Khaeca

dcrswBslmacpB

shos3raBcKk(ccaKuitT53lpecclciohcr

U.B. Jagtap, V.A. Bapat / Journal of E

nd cycloartobiloxanthone were isolated from the stem bark ofrtocarpus kemando showed cytotoxicity against KB (human oralpidermoid carcinoma) with an IC50 values 3.0, 0.5, 3.5, and.5 �g/ml, respectively, whereas, the compounds artonins E andrtobiloxanthone which have a catechol moiety in ring B, exhib-ted strong DNA strand scission activity (93% and 84% relaxation ofupercoiled DNA, respectively at 2.5 �g/ml concentration) (Seo etl., 2003). The two new isoprenylated flavones, artoindonesianins Und V have been isolated from the heartwood of Artocarpus chempe-en showed strong cytotoxicity against P-388 tumor cells with IC50.0 and 0.5 �g/ml, respectively (Syah et al., 2004). In another report,o et al. (2005) isolated new prenylated flavonoids, artelasto-eterol, artelasticinol, cycloartelastoxanthone, artelastoxanthonend cycloartelastoxanthendiol from the root bark of Artocarpuslasticus. The previously known compound artonol A exhibitedytotoxic activity against the A549 human cancer cell line, withn ED50 value of 1.1 �g/ml.

The flavonoids cycloartobiloxanthone and the xanthone artoin-onesianin C compounds were active against human epidermoidarcinoma of the nasopharynx (KB) cells; the chromone arto-igidusin, cycloartobiloxanthone and the xanthone artoindone-ianin C showed varying toxicity to human breast cancer (BC) cells,here as the flavonoid 7-demethylartonol E, xanthone artonol, flavonoid cycloartobiloxanthone and the xanthone artoindone-ianin C these compounds were active in the human small cellung cancer (NCI-H187) cytotoxicity assay, with artonol being the

ost active compound (IC50 1.26 �g/ml). The ellipticine was useds the standard drug in the test exhibited IC50 values against theseell lines at 1.33, 1.46 and 0.39 �g/ml, respectively. All these com-ounds were isolated from the root bark of Artocarpus rigidusLUME subsp. rigidus (Namdaung et al., 2006).

The prenylated flavones artoindonesianin A-2, artoindone-ianin A-3, heterophyllin, cudraflavone C, artoindonesianin Tave been isolated and identified from the chloroform extractf the heartwood of Artocarpus chempeden. These compoundshowed strong cytotoxic activity against murine leukemia P-88 cells with an IC50 value of 3.66, 5.45, 4.50, 4.50, 7.33 �M,espectively (Syah et al., 2006). The cycloartobiloxanthone andrtonin E have been isolated from the bark of Artocarpus rigidalume which have a high cytotoxicity against leukemia P-388ell (Suhartati et al., 2008). The cytotoxicity assay against theB, BC (human breast cancer) and Vero (African green mon-ey fibroblasts) cell line was determined; by Boonphong et al.2007). The nine prenylated flavones isolated from roots of Arto-arpus altilis viz. cycloartocarpin, artocarpin, chaplashin, morusin,udraflavone B, cycloartobiloxanthone, artonin E, cudraflavone C,rtobiloxanthone. These compounds showed cytotoxicity againstB, BC and Vero cell lines which were similar with the IC50 val-es of 2.9–14.7 �g/ml. Breadfruit (Artocarpus communis, Moraceae)

s cultivated in tropical and subtropical regions as a tradi-ional starch crop and also has potential medicinal properties.hree new geranyl chalcone derivatives including isolespeol;′-geranyl-2′,4′,4-trihydroxychalcone and 3,4,2′,4′-tetrahydroxy-′-geranyldihydrochalcone together with two known compounds

espeol and xanthoangelol were isolated from the leaves of Artocar-us communis and were studied for in vitro anticancer activity. Theffects of geranyl chalcone derivatives on the viability of humanancer cells [including human liposarcoma cells (SW 872), humanolorectal carcinoma cells (HT-29, COLO 205), human hepatocel-ullar carcinoma cells (PLC5, Huh7) and human hepatoblastomaells (HepG2, Hep3B)] were investigated. The results indicated that
solespeol showed the highest inhibitory activity with an IC50 valuef 3.8 �M in SW 872 human lip sarcoma cells. Treatment of SW 872uman lip sarcoma cells with isolespeol caused the loss of mito-hondrial membrane potentiality (DeltaPsim). Western blottingevealed that isolespeol stimulated increased protein expression of
harmacology 129 (2010) 142–166 149

Fas, FasL, and p53. The expression ratios of pro- and antiapoptoticBcl-2 family members were also changed by isolespeol treatmentto subsequently induce the activation of caspase-9 and caspase-3,which was followed by cleavage of poly(ADP-ribose) polymerase(PARP). These results demonstrated that isolespeol induced apop-tosis in SW 872 cells through Fas- and mitochondria-mediatedpathways (Fang et al., 2008a,b). The new oxepinoflavone, Artoin-donesianin E1 from the wood of Artocarpus elasticus, along withfour known prenylated flavones artocarpin, cycloartocarpin, cud-raflavones A and C. The cytotoxicity of compound artoindonesianinE1 against murine leukemia P-388 cells was studied using MTT(microculture tetrazolium technique) assay; which showed moder-ate cytotoxicity against P-388 cells with IC50 5.0 �g/ml (Musthapaet al., 2009). The cytotoxic effects of these compounds in humancancer cell might also have potential for anticancer application.These finding suggested that Artocarpus extracts have the poten-tial to be developed as new chemotherapeutic agents to prevent orto inhibit the growth of tumors and cancers.

3.6. Antiplatelet effects

The flavonoids, dihydroartomunoxanthone, cyclo-munomethanol, artochamins B and artocommunol CC wereisolated from the cortex of the roots of Artocarpus communisshowed antiplatelet effects on human platelet rich plasma (PRP).Out of the compounds tested in human PRP, compounds dihy-droartomunoxanthone, artochamins B and artocommunol CCshowed significant inhibition of secondary aggregation inducedby adrenaline and the antiplatelet effect of these compoundswere mainly owing to an inhibitory effect on thromboxaneformation. Platelet aggregation was an important pathogenicfactor in the development of atherosclerosis and associatedthrombosis in humans. Therefore, compounds dihydroartomunox-anthone, artochamins B and artocommunol CC are promising asantithrombotic agents (Weng et al., 2006).

3.7. Antifungal activity

Jayasinghe et al. (2004) performed antifungal activity-guidedfractionation of the n-butanol extract from the methanolextract of the leaves of Artocarpus nobilis and furnished2′,4′-4-trihydroxy-3′-geranylchalcone (1), 2′,4′-4-trihydroxy-3′[6-hydroxy-3,7-dimethyl-2(E),7-octadienyl] chalcone (2),2′,4′-4-trihydroxy-3′-[2-hydroxy-7-methyl-3-methylene-6-octaenyl] chalcone (3), 2′,3,4,4′-tetrahydroxy-3′-geranylchalcone(4), 2′,3,4,4′-tetrahydroxy-3′-[6-hydroxy-3,7-dimethyl-2(e), 7-octadienyl] chalcone (5). All these compounds showed goodfungicidal activity at 1 (5 �g/spot), 2 (5 �g/spot), 3 (5 �g/spot), 4(2 �g/spot) and compound 5 (15 �g/spot) against Cladosporiumcladosporioides on TLC bio-autography method. Benlate was usedas positive control. The chalcone 3 and 5 are new natural productswhere as 1 and 2 are reported first time from the family Moraceae.In another study Trindade et al. (2006) studied isolation and char-acterization of two novel chitin binding lectins from the seeds ofArtocarpus integrifolia (jackfruit) and Artocarpus incisa (breadfruit),these lectins denoted as jackin and frutackin, respectively. Boththe lectins inhibited the growth of Fusarium moniliformae andSaccharomyces cerevisae.

3.8. Antirotavirus/antidiarrhoeal activity

Goncalves et al. (2005) studied in vitro antirotavirus activ-ity of some medicinal plants used including Artocarpus in Brazilagainst diarrhoea. The plant species were screened for simian(SA-11) and human (HCR 3) rotaviruses inhibition in vitro. Theextracts from Artocarpus integrifolia L. bark (480 �g/ml) had antivi-

1 thnop

roTir

3

wtpibosuronrthortteAuaSat(paceBacgSrwtgthi2

3

idaaCatacf


al activity against both the viruses. They showed inhibitionf 99.2% for human rotavirus and 96.4% for simian rotavirus.herefore, the extracts of Artocarpus integrifolia can be usefuln the treatment of human diarrhoea if the etiologic agent is aotavirus.

.9. Antidiabetic activity

Investigations were carried out to evaluate the effects of hot-ater extracts of Artocarpus heterophyllus leaves on the glucose

olerance of normal human subjects and maturity-onset diabeticatients. The extracts of Artocarpus heterophyllus significantly

mproved glucose tolerance in the normal subjects and the dia-etic patients when investigated at oral doses equivalent to 20 g/kgf starting material (Fernando et al., 1991). Decoctions and infu-ions of Artocarpus communis (Forst) root bark are traditionallysed among the Yoruba-speaking people of Western Nigeria as folkemedies for the management, control and treatment of an arrayf human diseases, including type 2 diabetes mellitus. Althoughumerous bioactive prenylflavonoids have been isolated from theoots, stem bark and leaves of Artocarpus communis. The effects ofhe plant’s root bark extract on animal models of diabetes mellitusave hitherto not been reported in the biomedical literature. Theybserved that Artocarpus communis root bark aqueous extract (ACE)aised blood glucose concentrations in rats. Therefore they studiedhe glycaemic effect of ACE in comparison with that of streptozo-ocin (STZ) in Wistar rats. Four groups (A, B, C and D) of Wistar rats,ach group consisting of 10 rats, were used in this study. Grouprats received distilled water in quantities equivalent to the vol-

me of ACE administered. Diabetes mellitus was induced in thenimals in groups B and C by intra peritoneal (ip) injections ofTZ (75 mg/kg body weight). The rats in group C were addition-lly treated with ACE (50 mg/kg body weight) from the third to theenth day following the STZ treatment. Group D rats received ACE12.5–100 mg/kg body weight) only. The effects of ACE were com-ared with those of STZ on blood glucose concentrations, serumnd pancreatic insulin levels, hepatic hexokinase (HXK) and glu-okinase (GCK) activities, and hepatic glycogen contents in thexperimental animal paradigm used. The rats in treated groups, C and D exhibited pronounced polyuria, hypo-insulinaemiand hyperglycaemia. Group D rats developed significant hypergly-aemia (p < 0.05) immediately after ACE administration, whereasroups B and C rats became hyperglycaemic 24–72 h post STZ andTZ + ACE treatments, when compared with the control group Aats. Hepatic glycogen contents significantly increased (p < 0.05),hile HXK and GCK activities significantly decreased (p < 0.05) in

he treated groups B, C and D rats, when compared with the controlroup A rats. The findings of this laboratory animal study indicatedhat Artocarpus communis root bark aqueous extract induced acuteyperglycaemia in Wistar rats, and that it disrupted the biochem-

cal variables of the rat pancreas and liver (Adewole and Ojewole,007).

.10. Anti-inflammatory activity

The anti-inflammatory activities of the isolated flavonoids,ncluding cycloartomunin, cyclomorusin, dihydrocycloartomunin,ihydroisocycloartomunin, cudraflavone A, cyclocommunin, andrtomunoxanthone, and cycloheterohyllin, artonin A, artonin B,rtocarpanone, artocarpanone A, and heteroflavanones A, B, andfrom Artocarpus communis and Artocarpus heterophyllus, were

ssessed in vitro by determining their inhibitory effects onhe chemical mediators released from mast cells, neutrophils,nd macrophages. Compound dihydroisocycloartomunin signifi-antly inhibited the release of beta-glucuronidase and histaminerom rat peritoneal mast cells stimulated with P-methoxy-N-

harmacology 129 (2010) 142–166

methylphenethylamine. Artocarpanone significantly inhibited therelease of lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Compounds cycloheterohyllin, artonin B,and artocarpanone significantly inhibited superoxide anion for-mation in fMLP-stimulated rat neutrophils while compoundscyclomorusin, dihydrocycloartomunin, cudraflavone A, and cyclo-communin evoked the stimulation of superoxide anion generation.Compound artocarpanone exhibited significant inhibitory effecton NO (nitric oxide) production and iNOS (inducible nitric oxidesynthase) protein expression in RAW 264.7 cells. The potentinhibitory effect of compound artocarpanone on NO produc-tion in lipopolysaccharide (LPS)-activated macrophages, probablythrough the suppression of iNOS protein expression (Wei et al.,2005).

Phytochemical investigations of the ethyl acetate extracts of thefruits of Artocarpus heterophyllus has led to the isolation of phenoliccompounds artocarpesin [5,7,2′,4′-tetrahydroxy-6-(3-methylbut-3-enyl) flavone], norartocarpetin (5,7,2′,4′-tetrahydroxyflavone),and oxyresveratrol [trans-2,4,3′,5′-tetrahydroxystilbene]. The anti-inflammatory effects of these compounds were evaluated bydetermining their inhibitory effects on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activatedRAW 264.7 murine macrophage cells. These three compoundsexhibited potent anti-inflammatory activity. The results indi-cated that artocarpesin suppressed the LPS-induced productionof nitric oxide (NO) and prostaglandin E 2 (PGE 2) through thedown-regulation of inducible nitric oxide synthase (iNOS) andcyclooxygenase 2 (COX-2) protein expressions. Thus, artocarpesinmay provide a potential therapeutic approach for inflammation-associated disorders (Fang et al., 2008a,b).

3.11. Inhibitors of tyrosinase activity

The compound artocarpanone was tested by activity-guidedfractionation and this compound is a strong candidate as a remedyfor hyper pigmentation in human skin. Alteration in melanogeneismay be responsible for some of the clinical and histopatholog-ical features unique to malignant melanoma, a cancer with arapidly increasing incidence. Artocarpanone inhibited both mush-room tyrosinase enzyme activity and melanin production in B16melanoma cells with IC50 values of 80.8 and 89.1 �M, respec-tively (Arung et al., 2006a). Isoprenoid-substituted flavonoids wereisolated from the wood of Artocarpus heterophyllus by meansof activity-guided fractionation. Artocarpin, Cudraflavone C, 6-prenylapigenin, Kuwanon C, Norartocarpin and Albanin A inhibitedmelanin biosynthesis in B16 melanoma cells without inhibit-ing tyrosinase. A structure–activity investigation indicated thatthe presence of the isoprenoid-substituted moiety enhanced theinhibitory activity on melanin production in B16 melanoma cells(Arung et al., 2006b). From Artocarpus gomezianus, a dimericstilbene was isolated and this compound was found to havetyrosinase-inhibitory activity (Likhitwitayawuid and Sritularak,2001). The heartwood extract of Artocarpus lakoocha Roxb. wasevaluated for the in vitro tyrosinase-inhibitory activity and the invivo melanin-reducing efficacy in human volunteers. The IC50 ofthe extract and oxyresveratrol, its major active ingredient, againstmushroom tyrosinase was 0.76 and 0.83 �g/ml, respectively. Theextract dissolved in propylene glycol was subsequently tested infemale volunteers using a parallel clinical trial with self-control(n = 20 per group). The first group received the 0.25% (w/v) Arto-carpus lakoocha solution as the test solution, whereas the second
and the third group, respectively, received 0.25% licorice extractand 3% kojic acid as the reference solutions in the same solvent.Then each group were applied twice daily and the test (or refer-ence) solution in one of upper arm, whereas the remaining armwas treated with only propylene glycol (self-control) for 12 weeks.

thnop

TMmittlo(eiesoaoToaeieblodfmtattsdwa(mhmactTcbaodiAs2

3

pc5oiilca


he melanin content of each application site was measured usingexa meter every week and calculated as percent reduction inelanin content relative to the initial melanin value (% whiten-

ng). The value of percent whitening was then compared betweenhe product-treated and the propylene glycol-treated arms withinhe same subject using paired t-test (alpha = 0.05). The Artocarpusakoocha extract was the most effective agent giving the shortestnset of significant whitening effect after 4 weeks of applicationp < 0.05), followed by 3% Kojic acid (6 weeks) and 0.25% licoricextract (10 weeks). The effect also increased with time with max-mum whitening observed after 12 weeks for Artocarpus lakoochaxtract. When the extract was formulated as an oil-in-water emul-ion, its whitening efficacy was further enhanced. Daily applicationf 0.1% (w/w) Artocarpus lakoocha lotion to the upper arms (n = 25)nd cheeks (n = 15) of volunteers produced significant whiteningver the lotion base after 2 and 3 weeks, respectively (p < 0.05).hus, the preliminary study suggested that the heartwood extractf Artocarpus lakoocha might have a promising potential for use asn effective and economical skin-whitening agent (Tengamnuayt al., 2006). Thus this study was to clarify the melanogenesis-nhibitory and antioxidant activity of Thai breadfruit’s heartwoodxtract for application as a skin-lightening agent. The heartwood ofreadfruit (Artocarpus incisus) grown in Phitsanulok Province, Thai-

and, was extracted by using diethyl ether or methanol. The amountf artocarpin, a major component of Artocarpus incisus extract, wasetermined by using the HPLC method. The artocarpin contentound in ether extract was 45.19 ± 0.45% (w/w), whereas that in

ethanol extract was 19.61 ± 0.05% (w/w). The ether extract washen evaluated for tyrosinase-inhibitory, melanogenesis-inhibitorynd antioxidant activities. The tyrosinase-inhibitory activity wasested in vitro by monitoring the inhibition of the extract againsthe formation of DOPAchrome by tyrosinase enzyme. The resultshowed that the tyrosinase-inhibitory activity of the extract wasose-dependent. The obtained IC50 value was 10.26 ± 3.04 �g/ml,hile kojic acid, a well-known tyrosinase inhibitor, provided

n IC50 of 7.89 ± 0.18 �g/ml. Melanocyte B16F1 melanoma cellsATCC no. CRL-6323) were then used for determination of the

elanogenesis-inhibitory activity of the extract, comparing it toydroquinone, kojic acid, and purified artocarpin. The amount ofelanin produced by the cells was monitored by measuring an

bsorbance at 490 nm. The obtained results indicated that Arto-arpus incisus extract at a concentration of 2–25 �g/ml was ableo decrease the melanin production of the melanocyte B16F1 cells.he obtained micrograph also confirmed that the extract did nothange the cell morphology but reduced the melanin contenty inhibiting melanin synthesis, whereas the purified artocarpint a concentration of 4.5 �g/ml caused changes in cell morphol-gy. Additionally, the extract exhibited antioxidant activity in aose-dependent manner at an EC50 of 169.53 ± 9.73 �g/ml, accord-

ng to DPPH assay. Results indicated that the ether extract ofrtocarpus incisus heartwood has the potential of acting as akin-lightening agent for application in cosmetics (Donsing et al.,008).

.12. Inhibitors of 5-lipoxygenase activity

Natural compounds isolated from the Indonesian plant, Artocar-us communis, inhibited 5-lipoxygenase of cultured mastocytomaells. One of the five compounds, AC-5-1 (Artocarpus communis-1), strongly inhibits 5-lipoxygenase with a half-inhibition dosef 5 ± 0.12 × 10−8 M. However, prostaglandin synthesizing activ-
ty was not inhibited until 10−5 M. AC-5-l is a highly selectivenhibitor for 5-lipoxygenase. The AC-5-l at 10−5 M inhibits 96% ofeukotriene C4 synthesis of mouse peritoneal cells facilitated byalciumionophore. Arachidonic acid-induced ear edema of mice,n in vivo inflammatory model, involving leukotriene induction
harmacology 129 (2010) 142–166 151

was strongly inhibited by AC-5-l in a dose-dependent manner. Theinhibition was the strongest of any inhibitors of 5-lipoxygenasereported previously. Since the natural compound AC-5-l can selec-tively inhibited 5-lipoxygenase and affected in vivo inflammation,it will be interesting to investigate the role of leukotrienes oninflammation and other physiological processes (Koshihara et al.,1998).

3.13. Inhibitors of 5-˛ reductase activity

Artocarpin (Ar) is a naturally occurring compound isolatedfrom a diethyl ether extract of heartwood of Artocarpus incisus.Ar possesses potent 5-� reductase inhibitory effect resulting inthe inhibition of the conversion of testosterone into 5-�-dihydro-testosterone (Shimizu et al., 2000). The 5-� reductase inhibitorsacts on androgen receptors which are found in both preputialskin and nongenital skin. Therefore Ar might be useful in selectivetreatment of androgen-dependent disorders such as male patternalopecia and achne. The penetration of Ar into the deeper layers ofthe skin where androgen receptors are present is limited; becauseof skin which acts as a physical barrier. To treat these disorders,the compound must be delivered through skin. Pitaksuteepong etal. (2007) prepared alginate/chitosan (ACS) microparticles for tar-geted transfollicular delivery. A suitable particle size ranging from2 to 6 �M was prepared by using the ionotropic gelation technique.Entrapment efficiency of Ar from the ACS microparticles over 6 hwas 0.7% of the loading dose suitable for a long-term release ofAr in follicular ducts. The optimal growth suppression of the ham-ster flank organs could be achieved by topical application of Ar-ACSmicroparticles with a content of 0.1 mg in 5 mg microparticles toone hamster flank while the other flank (intra species control)showed the normal growth of the flank organs and Ar at the sameconcentration in solution form could not suppress the growth of theflank organs to the same extent. The efficiency of Ar 0.1 mg loaded inACS microparticles was shown to be comparable to a dose of 1 mgAr applied as solution. However, Ar formulated in microparticlesdid not show significant systemic action compared to the dermalapplication of an Ar solution and a flutamide preparation (1 mg) as apositive control. These results suggested that ACS-Ar microparticlesmight be a promising delivery system for the surface treatment ofandrogen-dependent disorders such as achne, seborrhea hirsutismand androgenic alopecia.

3.14. Antiarthritic effect

The leaves and roots of Artocarpus tonkinensis are used in tradi-tional medicine for the treatment of backache and rheumatic jointdiseases. Rheumatoid arthritis (RA) is a chronic inflammatory dis-ease characterized by joint manifestation leading to the cartilagedestruction and bone erosion. The ethyl acetate extract of leavesfrom Artocarpus tonkinensis was tested for its anti-inflammatoryproperties in collagen induced arthritis (CIA) in dark agouti ratsby means of immunization with collagen type II (C II) emulsifiedin incomplete Freunds adjuvant. The rats were treated daily withintraperitoneal injection of Artocarpus extract at the day of immu-nization. Arthritis progression was measured by means of clinicalscoring of paws and anti-CII antibody titres were measured byELISA. In vitro lymph node (LN) cell cultures were treated with Arto-carpus extract and the apoptosis inducing effect was determinedwith FACS staining by using annexin V and propidium iodide as wellas TUNEL (terminal deoxynucleotidyl transferase nick end label-
ing) method. Treatment of rats with Artocarpus extract decreasedarthritis incidence and severity and delayed disease onset. Whentreatment was started after the onset of arthritis, showed tendencytowards arthritis amelioration. In vitro Artocarpus extract acted asa T-cell modulators inhibiting mitogen-induced T-cell proliferation

1 thnop

ae

abm(6[5‘foaafTaTpidsai

3

AtwnastetA

3

pgme1amoat1ciw1crpitcit


nd inducing apoptosis of activated LN-derived lymphocytes (Ngoct al., 2005).

Dang et al. (2009) have isolated four individualctive components from Artocarpus tonkinensis extracty (RP-HPLC) reverse phase high-pressure liquid chro-atography. A novel biologically active flavonoid glucoside

5-hydroxy-8-hydroxymethyl-8-methyl-2-[4-(3,4,5-trihydroxy--hydroxymethyl-tetrahydro-pyran-2-yloxy)-phenyl]-8H-pyrano3,2-g] chromen-4-one) with an average molecular mass of14.49 Da and named as artonkin-4′O-glucoside. The name

artonkin’ for the novel flavonoid part of the compound was coinedrom the Latin name of its source Artocarpus tonkinensis. The threether active flavonoid glucosides isolated and characterized werelphitonin-4-O-�-d-glucoside, maesopsin-4-O-�-d-glucosidend kaempherol-3-O-�-d-glucoside. All four compounds wereound to cause anti-inflammatory effect with different potencies.he anti-inflammatory effects demonstrated in the rat model ofrthritis correlate well with the inhibition of mitogen-induced-cell proliferation. Furthermore, the compounds inhibited theroduction of cytokines, such as tumor necrosis factor-� and

nterferon-�, in mitogen-stimulated T cells in a concentration-ependent manner. They postulate that the isolated flavonoidsuppressed T-cell proliferation as well as cytokine expressionnd thereby contributed to an amelioration of arthritis severityn CIA.

.15. Antiatherosclerotic activity

The cytoprotective effects of various solvent extracts ofrtocarpus altilis (Parkinson) Fosberg were evaluated. The cytopro-ective effects were determined in human U937 cells incubatedith oxidized LDL (OxLDL) using the 4-[3-(4-iodophenyl)-2-(4-itrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1)ssay. The results demonstrated that the ethyl acetate extracthowed cytoprotective activities. To identify the main cytoprotec-ive components, a bioassay guided isolation of the ethyl acetatextract afforded �-sitosterol and six flavonoids. The cytoprotec-ive effect offers good prospects for the medicinal applications ofrtocarpus altilis (Wang et al., 2006).

.16. Anthelmintic effect

The effect of the crude extract of Artocarpus lakoocha (70% com-osition is 2,4,3′,5′-tetrahydroxystilbene – THS) on adult Fasciolaigantica was evaluated after incubating the parasites in M-199edium containing 250, 500, 750 and 1000 �g/ml of the crude

xtract, or triclabendazole (TCZ) at the concentrations of 80 and75 �g/ml as the positive control, for 3, 6, 12 and 24 h, using rel-tive motility (RM) assay and observation by scanning electronicroscope (SEM). Decreased contraction and motility were first

bserved after 3 h incubation with TCZ at the concentration 80nd 175 �g/ml. TCZ markedly reduced the parasite’s motility athe concentration of 175 �g/ml at 6 h, and killed the worms after2 h exposure. The crude extract of Artocarpus lakoocha at all con-entrations reduced the parasite’s motility similar to TCZ at 3 hncubation. In 250 and 500 �g/ml of the crude extract, the values

ere decreased from 3 to 12 h, and then they were stable between2 and 24 h and reduced to the level approximately 30–40% of theontrol. At 750 and 1000 �g/ml concentrations, the crude extractapidly reduced the RM values from the start to 12 h and killed thearasites between 12 and 24 h incubation. The crude extract also

nhibited the larval migration by 75% and 100% at the concentra-ions of 250–500 and 750–1000 �g/ml, respectively. TCZ and therude extract caused sequentially changes in the tegument includ-ng swelling, followed by blebbings that later ruptured, leadingo the erosion and desquamation of the tegument syncytium. As

harmacology 129 (2010) 142–166

the result, lesion was formed which exposed the basal lamina.The damage appeared more severe on the dorsal than the ven-tral surface, and earlier on the anterior part and lateral marginswhen compared to the posterior part. The severity and rapidity ofthe damages were enhanced with increasing concentration of thecrude extract. Hence, the crude extract of Artocarpus lakoocha, mayexert its fasciolicidal effect against adult Fasciola gigantica by ini-tially causing the tegumental damage (Saowakon et al., 2009). Theresults were supported the utilization of Artocarpus lakoocha Roxb.in traditional medicine used by indigenous people in Thailand andLaos as anthelmintics (Salguero, 2003).

3.17. Antioxidant activities

The natural antioxidants in fruits and vegetables gained increas-ing interest among food scientists, nutrition specialists andconsumers, as they reduce the risk of chronic diseases and promotehuman health. The antioxidant properties of prenylflavones, cyclo-heterophyllin and artonins A and B inhibited iron-induced lipidperoxidation in rat brain homogenate, scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH), scavenged peroxyl radicals, hydroxylradicals that were generated by 2,2′-azobis (2-amidinopropane)dihydrochloride and the Fe3+–ascorbate–EDTA–H2O2 system,respectively. However, they did not inhibit xanthine oxidaseactivity or scavenge superoxide anion, hydrogen peroxide,carbon radical, or peroxyl radicals derived from 2,2′-azobis(2,4-dimethylvaleronitrile) in hexane. Moreover, cycloheterophyllinand artonins A and B inhibited copper-catalyzed oxidation ofhuman low-density lipoprotein, as measured by fluorescenceintensity, thiobarbituric acid-reactive substance and conjugated-diene formations and electrophoretic mobility. It is concluded thatcycloheterophyllin and artonins A and B served as powerful antiox-idants against lipid peroxidation when bio membranes are exposedto oxygen radicals (Ko et al., 1998).

The total antioxidant capacity and phenolic content of edibleportions and seeds of jackfruit were studied. The seeds showedmuch higher antioxidant activity and phenolic content than theedible portions (Soong and Barlow, 2004; Jagtap et al., 2010).

The prenylated flavonoid, 5,7,40-trihydroxy-6,8-diprenylisoflavone, isolated from Artocarpus heterophyllus Lam.which showed stronger inhibitory effect on lipid peroxidationby interaction of hemoglobin and hydrogen peroxide, than thatof genistein, a non-prenylated isoflavone (Toda and Shirataki,2006). The ethanolic extracts of Artocarpus heterophyllus showedtheir abilities of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH)free radical (IC50 410 �g/ml). The IC50 of the ethanolic extractsof Artocarpus heterophyllus, Annona squamosa, Terminalia bellirica,Syzygium samarangense, Averrhoa carambola and Olea europa were410, 250, 34, 200, 30 and 76 �g/ml, respectively (Soubir, 2007).

Artelastin, a prenylated flavone previously isolated from Arto-carpus elasticus, was evaluated for its effect on the production ofreactive oxygen species (ROS) by human polymorphonuclear neu-trophils (PMNs) and nitric oxide (NO) by J774 murine macrophagecell line. Artelastin showed to be an inhibitor of ROS productiondue to a strong O2-scavenging activity. No effect was observed onthe activity of myeloperoxidase (MPO). Artelastin showed also tobe an inhibitor of NO production without NO-scavenging activ-ity. This flavone seems to interfere with the expression of theinducible nitric oxide synthase (iNOS) immediately after LPS-IFN gamma-macrophage stimulation (Cerqueira et al., 2008). Theflesh and seeds from Artocarpus odoratissimus were analyzed
for total antioxidant activity, total polyphenol, total flavonoidand total anthocyanin contents. The seed extract showed higherDPPH-scavenging activity (13.69 mg AEAC/g) and also FRAP ferricreducing ability (208.67 �M ferric reduction to ferrous in 1 g of drysample) as compared to the flesh which showed 2.44 mg AEAC/g

thnop

Da

ccaacepaa2at4iAonTafii

3

fdmbdbum(cildcitpit2iobt2

4

aiaAewc


PPH scavenging and 116.7 �M ferric reduction activity (Bakar etl., 2009).

In another study Lin et al. (2009) isolated prenylflavonoids,yclogeracommunin, artoflavone A, artomunoisoxanthone, arto-ommunol CC, artochamin D, artochamin B, dihydroartomunox-nthone, isolated fromthe cortex of roots Artocarpus communis,nd known compounds, cycloartelastoxanthone, artelastoheterol,ycloartobiloxanthone and artonol A, isolated from Artocarpuslasticus, all showed inhibition of oxidative DNA damage. The com-ounds artoflavone A, cycloartelastoxanthone, artelastoheterol,nd cycloartobiloxanthone significantly showed DPPH-scavengingctivity with IC50 values of 24.2 ± 0.8, 18.7 ± 2.2, 42.2 ± 2.8 and6.8 ± 1.2 �M, respectively, while compounds cyclogeracommuninnd artonol A significantly displayed inhibitory effects on xan-hine oxidase (XO) activity with IC50 values of 73.3 ± 19.1 and3.3 ± 8.1 �M, respectively. These compounds may serve as antiox-

dant agents for the treatment of free radical-induced disease. Thertocarpus species are rich source of phenolic compounds and offerspportunities for develop value added products from edible fruits,eutraceuticals and food applications to enhance health benefits.he radical scavenging activities of phytochemicals were evalu-ted by the in vitro assays and it will be interesting to investigateurther antioxidative potential of these compounds in prevent-ng various radical mediated injuries in pathological situationsn vivo.

.18. Corneal epithelial wound healing

The corneal epithelial wound healing properties of KM+ a lectinrom Artocarpus integrifolia induces neutrophil migration wereetermined in rabbits as it induces neutrophil migration. A 6.0-m diameter area of debridement was created on the cornea of

oth eyes by mechanical scraping. The experimental eyes receivedrops of KM+ (2.5 �g/ml) every 2 h, while the control eyes receiveduffer. The epithelial wounded areas of the lectin-treated andntreated eyes were stained with fluorescein, photographed andeasured. The animals were killed 12 h (group 1, n = 5), 24 h

group 2, n = 10) and 48 h (group 3, n = 5) after the scraping. Theorneas were analyzed histologically (haematoxylin and eosin andmmunostaining for proliferation cell nuclear antigen, p63, vascu-ar endothelial growth factor, c-Met and laminin). No significantifferences were found at the epithelial gap between treated andontrol eyes in the group 1. However, the number of neutrophilsn the wounded area was significantly higher in treated eyes inhis group. Three control and seven treated eyes were healed com-letely and only rare neutrophils persisted in the corneal stroma

n group 2. No morphological distinction was observed betweenreated and control eyes in group 3. In treated corneas of group, there was an increase in immunostaining of factors involved

n corneal healing compared to controls. Thus, topical applicationf KM+ may facilitate corneal epithelial wound healing in rabbitsy means of a mechanism that involved increased influx of neu-rophils into the wounded area induced by the lectin (Chahud et al.,009).

. Conclusion

The present review discusses the significance of Artocarpus asvaluable source for medicinally important compounds besides

ts edible fruit which is a store house of minerals, vitamins,
ntioxidants and other nutrients. It provides rich opportunities forrtocarpus spp. especially from the fresh fruits of Artocarpus het-rophyllus, Artocarpus altilis and Artocarpus chempeden which existithin the arena of functional foods and beverages. The antioxidant
onstituents present in the fruits play important role in scavenging

harmacology 129 (2010) 142–166 153

free radicals and reactive oxygen species which are responsible fornumber of human disorders. The Artocarpus fruits and fruit prod-ucts hold potential in the diet as they possess not only pleasanttaste but also source of naturally and readily available source ofinstant energy.

Reports for biological activity of species of Artocarpus arenumerous, but phytochemical investigations have been conductedonly on a few Indonesian species. Phenolic compounds includingflavonoids, stilbenoids and arylbenzofurons seem to be typical ofthe genus as they were detected in several species. Correlationbetween the ethnomedical employment and the pharmacologi-cal activities has been duly observed and described in the presentreview. Significant activity of the prenylated stilbenes and flavonesisolated from certain species against Plasmodium has been reported(Namdaung et al., 2006; Boonphong et al., 2007; Widyawaruyantiet al., 2007).

Crude extracts and phytochemicals isolated from Artocarpusheterophyllus, Artocarpus communis (Artocarpus altilis), Artocarpusnobilis, Artocarpus rigida, as reviewed here have been found to haveantibacterial activity (Sato et al., 1996; Khan et al., 2003; Suhartatiet al., 2008), antifungal activity (Jayasinghe et al., 2004; Trindadeet al., 2006), antidiarrhoeal activity (Goncalves et al., 2005), antidi-abetic activity (Adewole and Ojewole, 2007). The phytomedicinesare complex mixtures of compounds and exert more pronouncedeffects than individual compounds (Heinrich et al., 2005). The roleof such complex mixtures and the ‘ideal’ composition of an activeextract needs to be investigated first using a combination of in vitro(or in vivo animal) techniques in combination with phytochemicalor metabolomic techniques (Verpoorte et al., 2005).

Another traditional use of Artocarpus lakoocha has been inthe treatment of tapeworm infection. Seventy percent of thecrude aqueous extract of Artocarpus lakoocha composed of pheno-lic compound, 2,4,3′,5′-tetrahydroxystilbene (THS). The chemicalstructure of THS is similar to that of halogenated phenolic-fasciolocides. Hence, it is possible that THS could acts as a drugfor the treatment of liver fluke infection in cattle and human(Saowakon et al., 2009).

Research summarized here also indicated that phytochemicalsisolated from heartwood extract of, Artocarpus gomezianus, Arto-carpus heterophyllus, Artocarpus incisus (Artocarpus altilis) and Arto-carpus lakoocha (Artocarpus lacucha) showed tyrosinase-inhibitoryactivity, which had the potential of acting as a skin-lightening agentfor application in cosmetics (Likhitwitayawuid and Sritularak,2001; Arung et al., 2006a,b; Donsing et al., 2008).

Pharmacological and chemical studies have demonstrated anti-inflammatory activity of pure compounds. Of particular promise,due to their potent cytotoxic activity against a number of can-cer cell lines, are the prenylated flavones and flavonoids, In fact,these finding suggested that Artocarpus species have the poten-tial to be developed as new chemotherapeutic agents to preventor to inhibit the growth of tumors and cancers (Suhartati et al.,2001; Ko et al., 2005; Syah et al., 2004; Namdaung et al., 2006;Syah et al., 2006; Boonphong et al., 2007; Musthapa et al., 2009). Inaddition to these cytotoxic compounds, several flavonoids, includ-ing other phenolic compounds demonstrated antioxidant activities(Soubir, 2007; Cerqueira et al., 2008), anti-inflammatory activities(Wei et al., 2005; Fang et al., 2008a,b), antiatherosclerotic activ-ity (Wang et al., 2006), antiplatelet activity (Weng et al., 2006) andantiviral activity (Likhitwitayawuid et al., 2005, 2006). The differentpharmacological activities of Artocarpus extracts and isolated sec-ondary metabolites have only been assayed by in vitro tests using
laboratory animals, but these results obtained are not compatibleto the situation in humans. There is a need to minimize the gapbetween the studies conducted so far and to exploit fully medic-inal properties of Artocarpus. However, there is a need to studythe acute toxicity, sub acute toxicity, chronic toxicity and phar-

1 thnop

mct

pcKJitiitoafi(cd

Ftsusw

A


acological safety profiling of plants. Detailed animal acute andhronic toxicity studies of compounds are required prior to clinicalesting.

Furthermore, lectins which are glycoproteins are abundantlyresent in jackfruit seeds having wide applications in biochemistry,ell biology and medicines (Rudiger and Gabius, 2001). As stated byabir (1998), the abundance of source material for the production of

acalin – lectin, its ease of purification, yield and stability have madet an attractive cost effective lectin. The Jacalin completely blockshe HIV-1 infection in vitro infection of lymphoid cells, by interact-ng with the CD4, which is a high affinity receptor to HIV. Hence,t should be explored whether Jacalin can be used as a therapeu-ic agent for various ailments including HIV as well as modulationf immune response to pathogens (Favero et al., 1993; Corbeau etl., 1994; Tamma et al., 2003). The topical application of KM+ mayacilitate corneal epithelial wound healing in rabbits by increasingnflux of neutrophils into the wounded area induced by the lectinChahud et al., 2009). Once the usefulness of Jacalin is confirmedonclusively, will be a good candidate for formulating an efficientrug.

Two goals seem to be largely open for future exploitation.irst, once the accurate and precise chemical composition of
hese compounds is known, will lead further studies to under-tand metabolic pathways of these useful products, and second,nderstanding metabolic engineering will enhance the synthe-is and accumulation of these compounds considerably. Thisill be aided by application of molecular marker technology for
ppendix A. Constituents of Artocarpus

Class of compound Name ofcompound

Structurea

Chalcone Kanzonol C

ArtoindonesianinJ

Flavanone Artocarpanone

ArtoindonesianinE

harmacology 129 (2010) 142–166

identifying high yielding clones producing these products andalso by the extraction and cloning of various genes involved inmetabolic pathways of useful products. However, the metabolicpathways by which active compounds are biosynthesized aremostly poorly understood, and relatively few genes for key enzy-matic or regulatory steps have been isolated (Canter et al., 2005).New progress and findings in understanding product synthesis inplant metabolism will undoubtedly expand the range and preci-sion for yielding a superior material (Canter et al., 2005). On thebasis of biological activities of Artocarpus species, crude extractand derived phytochemicals and their uses as neutraceuticals andpharmacological agents in traditional and modern research arepossible but will first require clinical trials and product devel-opment. The current evidence is large limited to in vitro data.Artocarpus species is a very important part of biodiversity andit’s sustainably use for future generations. The jackfruit still isa rather an untapped source for isolation and characterizationof novel useful products; however, at the same time it alsoopens up new avenues for novel therapeutics for fighting dreadeddisease.

Acknowledgements

Emeritus scientist fellowship to VAB and junior research fellow-ship to UBJ from Council of Scientific and Industrial Research (CSIR),New Delhi, India is gratefully acknowledged.

Source Biological activity

Artocarpus bracteata NR

Artocarpus bracteata NR

Artocarpus chempeden CytotoxicAntidiarrhoealTyrosinase inhibitor

Artocarpus chempeden Cytotoxic


Appendix A (Continued )Class of compound Name of

compoundStructurea Source Biological activity

HeteroflavanoneA

Artocarpus chempeden Antidiarrhoeal

Flavone Norartocarpetin Artocarpus chempedenArtocarpus scortechiniiArtocarpus kemandoArtocarpus gomezianus

Tyrosinase inhibitor

6-(3-Methylbutyl-2-enyl)apigenin

Artocarpus bracteataArtocarpus gomezianus

NR

Carpachromene Artocarpus bracteata NR

Flavan-3-ol Afzelechin Artocarpus fretessiArtocarpus reticulatus

NR

Afzelechinrhamnoside

Artocarpus fretessiArtocarpus reticulatus

NR

Cathecin Artocarpus fretessiArtocarpus reticulatus

NR

3-Prenylflavone Artocarpin Artocarpus chempedenArtocarpus maingayiiArtocarpus kemandoArtocarpus altilis

CytotoxicTyrosinase inhibitor5-� reductase inhibitorAntitubercular




Cudraflavone C Artocarpus chempedenArtocarpus glaucus

CytotoxicAntitubercularTyrosinase inhibitor

ArtoindonesianinQ

Artocarpus chempeden NR

ArtoindonesianinR


Heterophyllin Artocarpus chempeden Cytotoxic

ArtoindonesianinU


Artonin E Artocarpus scortechiniiArtocarpus rotundaArtocarpus rigidaArtocarpus altilis

AntibacterialAntimalarialAntitubercularCytotoxic

ArtoindonesianinL

Artocarpus rotunda Cytotoxic




ArtoindonesianinG

Artocarpus lanceifolius Cytotoxic

ArtoindonesianinH


ArtioindonesianinI


Artelastofuran Artocarpus lanceifolius NR

Artelasticin Artocarpus lanceifolius Cytotoxic

14-HydroxyartoninE

Artocarpus lanceifolius NR




Morusin Artocarpus altilis AntimalarialAntitubercularCytotoxic

Mulberrin Artocarpus fretessi NR

Mulberrochromene Artocarpus fretessi NR

Oxepinoflavone ArtoindonesianinB

Artocarpus chempedenArtocarpus altilis

Cytotoxic

Chaplashin Artocarpus chempedenArtocarpus maingayiiArtocarpus kemandoArtocarpus altilis

AntimalarialAntitubercularCytotoxic

Pyrano-flavone Cyclocomunol Artocarpus chempeden Cytotoxic

Cyclocommunin Artocarpus chempeden Cytotoxic




Cycloartocarpin Artocarpus chempedenArtocarpus maingayiiArtocarpus kemandoArtocarpus altilis


Artoindonesianin Artocarpus chempeden Cytotoxic

5′HydroxycudraflavoneA

Artocarpus chempedenArtocarpus teysmanii

NR

Cycloheterophyllin Artocarpus chempeden Anti-inflammatoryAntioxidant

Artelastin Artocarpus lanceifolius CytotoxicAntioxidant

Artelastochromene Artocarpus lanceifolius Cytotoxic




Cudraflavone A Artocarpus maingayii CytotoxicAnti-inflammatory

Dihydrobenzoxanthone ArtoindonesianinS


ArtoindonesianinT


ArtoindonesianinV


Artonin B Artocarpus chempeden Anti-inflammatory

Artobiloxanthone Artocarpus lanceifoliusArtocarpus teysmaniiArtocarpus scortechinii

CytotoxicAntimalarial




Furanodihydo-benzoxanthone ArtoindonesianinA


Artonin A Artocarpus chempeden Anti-inflammatory

ArtoindonesianinM


Cylcoartobiloxanthon-e

Artocarpus lancefoliusArtocarpus teysmaniiArtocarpus scortechiniiArtocarpus rotundaArtocarpus rigidaArtocarpus kemandoArtocarpus altilis


Artonin M Artocarpus rotunda Cytotoxic

Artonin J Artocarpus teysmanii NR




ArtoindonesianinP

Artocarpus lancefolius Cytotoxic

ArtoindonesianinZ-1


Pyranodihydrobenzo-xanthone ArtoindonesianinZ-2


Quinonodihydroxanthone Artonin O Artocarpus rotunda Cytotoxic

Cyclopenteno-xanthone ArtoindonesianinC

Artocarpus teysmaniiArtocarpus scortechinii

Cytotoxic

Xanthonolide Artonol B Artocarpus lancefoliusArtocarpus teysmaniiArtocarpus scortechiniiArtocarpus altilis

Cytotoxic

Dihydro-xanthone Artonol A Artocarpus scortechinii NR



compoundStructurea Source Biological

activity

Cyclopenteno-chromone ArtoindonesianinZ-3


Stilbene ArtoindonesianinF

Artocarpus altilis NR

Oxyresveratrol Artocarpus gomezianusArtocarpus reticulatus

AntiviralCytotoxicAnti-HSVAnti-HIV

ArtoindonesianinN

Artocarpus gomezianus NR

2-Arylbenzofuran ArtoindonesianinX

Artocarpus fretessi NR

ArtoindonesianinY

Artocarpus fretessi NR

ArtoindonesianinO

Artocarpus gomezianus NR

NR = not reported.a Hakim et al.

1 thnop

R

A

A

A

A

A

B

B

B

B

B

B

B

B

B

B

C

C

C

C

C

C

C

C

C

C

C

C

C

D


eferences

dewole, S.O., Ojewole, J.O., 2007. Hyperglycaemic effect of Artocarpus communisForst (Moraceae) root bark aqueous extract in Wistar rats. Cardiovascular Journalof Africa 18, 221–227.

jayi, I.A., 2008. Comparative study of the chemical composition and mineral ele-ment content of Artocarpus heterophyllus and Treculia Africana seeds and seedoils. Biresource Technology 99, 5125–5129.

ndrade, A.F.B., Saraiva, E.M.B., 1999. Lectin binding properties of different Leishma-nia species. Parasitology Research 85, 576–581.

rung, E.T., Shimizu, K., Kondo, R., 2006a. Inhibitory effect of artocarpanone fromArtocarpus heterophyllus on melanin biosynthesis. Biological and PharmaceuticalBulletin 29, 1966–1969.

rung, E.T., Shimizu, K., Kondo, R., 2006b. Inhibitory effect of isoprenoid-substitutedflavonoids isolated from Artocarpus heterophyllus on melanin biosynthesis.Planta Medica 72, 847–850.

abitha, S., Soccol, C.R., Pandey, A., 2007. Solid state fermentation for the pro-duction of Monascus pigments from jackfruit seed. Bioresource Technology 98,1554–1560.

akar, M.F.A., Mohamed, M., Rahmat, A., Fry, J., 2009. hytochemicals and antioxidantactivity of different parts of bambagan (Mangifera pajang) and tarap (Artocarpusodoratissimus). Food Chemistry 113, 479–483.

albach, A., Boarim, D.S.F., 1992. As frutas na medicina natural. Editora Missionaria,Sao Paulo.

anerjee, R., Dhanaraj, V., Mahanta, S.K., Surolia, A., Vijayan, M., 1991. Preparationand X-ray characterization of four new crystal forms of Jacalin, a lectin fromArtocarpus integrifolia. Journal of Molecular Biology 221, 773–776.

arre, A., Peumans, W.J., Rossignol, M., Boederies, G., Culerrier, R., Van Damme,E.J.M., Rogue, P., 2004. Artocarpin is a polyspecific Jacalin-related lectin withmonosaccharide preference for mannose. Biochimie 86, 685–691.

asu, D., Delucas, L., Parks, E.H., Suddhat, F.L., 1988. Preliminary crystallographicstudy of the �-d galactose specific lectin from jackfruit (Artocarpus integra)seeds. Journal of Molecular Biology 201, 661–662.

oonlaksiri, C., Oonanant, W., Kongsaeree, P., Kittakoop, P., Tanticharoen, M.,Thebtaranonth, Y., 2000. An antimalarial stilbene from Artocarpus integer. Phy-tochemistry 54, 415–417.

oonphong, S., Baramee, A., Kittakoop, P., Puangsombat, P., 2007. Antitubercular andantiplasmodial prenylated flavones from the roots of Artocarpus altilis. ChiangMai Journal of Science 34, 339–344.

ose, T.K., 1985. Jackfruit. In: Mitra, B.K. (Ed.), Fruits of India: Tropical and Subtrop-ical. Naya Prokas, Culcutta, pp. 488–497.

unn-Moreno, M.M., Campos-Neto, A., 1981. Lectin extracted from the seeds of Arto-carpus intregrifolia (jackfruit): potent and selective stimulator of distinct humanT and B cell functions. Journal of Immunology 127, 427–429.

anter, P.H., Thomas, H., Ernst, E., 2005. Bringing medicinal plants into cultivation:opportunities and challenges for biotechnology. Trends in Biotechnology 23,180–185.

erqueira, F., Cidade, H., Van Ufford, L., Beukelman, C., Kijjoa, A., Nascimento, M.S.,2008. The natural prenylated flavone artelastin is an inhibitor of ROS and NOproduction. International Immunopharmacology 8, 597–602.

hahud, F., Ramalho, L.N.Z., Ramalho, F.S., Haddad, A., Roque-Barreira, M.C., 2009.The lectin KM+ induces corneal epithelial wound healing in rabbits. InternationalJournal of Experimental Pathology 90, 166–173.

handrika, U.G., Jansz, E.R., Warnasuriya, N.D., 2005. Analysis of carotenoids in ripejackfruit (Artocarpus heterophyllus) kernel and studied their bioconversion inrats. Journal of the Science of Food and Agriculture 85, 186–190.

haroenlarp, P., Radomyos, P., Harinasuta, T., 1981. Treatment of taeniasis withPuag-Haad: a crude extract of Artocarpus lakoocha wood. The Southeast AsianJournal of Tropical Medicine and Public Health 12, 568–570.

hatterjee, B.P., Ahmed, H., Chowdhury, S., 1988. Further characterization of Artocar-pus lakoocha lectin (Artocarpin) purified using Rivanol. Carbohydrate Research180, 97–110.

hatterjee, B.P., Vaith, P., Chatterjee, S., Karduck, D., Uhlenbruck, G., 1979. Com-parative studies of new marker lectins for alkali-labile carbohydrate chains inglycoproteins. International Journal of Biochemistry 10, 321–327.

howdhury, F.A., Raman, Md.A., Mian, A.J., 1997. Distribution of free sugars and fattyacids in jackfruit (Artocarpus heterophyllus). Food Chemistry 60, 25–28.

howdhury, S., Ahmed, H., Chatterjee, B.P., 1987. Purification and characterization ofan �-d-galactosyl binding lectin from Artocarpus lakoocha seeds. Asian Journalof Plant Sciences 159, 137–148.

howdhury, S., Ahmed, H., Chatterjee, B.P., 1991. Chemical modification studies ofArtocarpus lakoocha lectin artocarpin. Biochimie 73, 563–571.

huanasa, T., Jurairatana, P.J., Lipipun, V., Likhitwitayawuid, K., Suzuki, M.,Pramyothin, P., Hattori, M., Shiraki, K., 2008. Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: mechanismof action therapeutic efficacy on cutaneous HSV-1 infection in mice. AntiviralResearch 80, 62–70.

ollin, L., Franzblau, S.G., 1997. Microplate Alamar Blue assay verses BACTEC 460system for high-throughput screening of compound against Mycobacteriumtuberculosis and Mycobacterium avium. Antimicrobial Agents and Chemotherapy
41, 1004–1009.
orbeau, P., Haran, M., Binz, H., Devaux, C., 1994. Jacalin, a lectin with anti-HIV-1properties, and HIV-1 gp120 envelope protein interact with distinct regions ofthe CD4 molecule. Molecular Immunology 31, 569–575.

ang, D.T.N., Eriste, E., Liepinsh, E., Trinh, T.T., Harris, H.E., Sillard, R., Larsson, P.,2009. A novel anti-inflammatory compound artonin-4′-o-glucoside from the

harmacology 129 (2010) 142–166

leaves of Artocarpus tonkinensis suppresses experimentally induced arthritis.Scandinavian Journal of Immunology 69, 110–118.

Das, P., Goswami, K., Chinniah, S., Panda, A., Banerjee, N., Sahu, S., Achari, N.P.B., 2007.Woodfordia fruticosa: traditional uses and recent findings. Journal of Ethnophar-macology 110, 189–199.

Da Silva, L.L.P., de Molfetta-Machado, J.B., Panunto-Castelo, A., Denecke, J., Goldman,G.H., Roque-Barreira, M.C., Goldman, M.H.S., 2005. cDNA cloning and functionalexpression of Km+, the mannose binding lectin from Artocarpus integrifolilaseeds. Biochimica et Biophysica Acta 1726, 251–260.

De Miranda-Santos, I.K.F., Mengel Jr., J.O., Bunn-Moreno, M.M., Campos-Neto, A.,1991. Activation of T and B cells by crude extract of Artocarpus integrifolia ismediated by a lectin distinct from Jacalin. Journal of Immunological Methods140, 197–203.

Desjardins, R.E., Canfield, C.J., Haynes, J.D., Chulay, J.D., 1979. Quantitative assess-ment of antimalarial activity in vitro by a semi automated microdilutiontechnique. Antimicrobial Agents and Chemotherapy 16, 710–718.

Dhanaraj, V., Patanjali, S.R., Surolia, A., Vijayan, M., 1988. Preparation and prelim-inary X-ray studies of two crystal forms of Jacalin, a lectin from Artocarpusintegrifolia. Journal of Molecular Biology 203, 1135–1136.

Donsing, P., Limpeanchob, N., Viyoch, J., 2008. Evaluation of the effect of Thaibreadfruit’s heartwood extract on melanogenesis-inhibitory and antioxidationactivities. Journal of Cosmetic Science 59, 41–58.

Fang, S.C., Hsu, C.L., Yen, G.C., 2008a. Anti-inflammatory effects of phenoliccompounds isolated from the fruits of Artocarpus heterophyllus. Journal of Agri-cultural and Food Chemistry 56, 4463–4468.

Fang, S.C., Hsu, C.L., Yu, Y.S., Yen, G.C., 2008b. Cytotoxic effects of new geranylchalcone derivatives isolated from the leaves of Artocarpus communis in SW872 human liposarcoma cells. Journal of Agricultural and Food Chemistry 56,8859–8868.

Faria, A.F., Rosso, V.V., Mercadante, A.Z., 2009. Carotenoid compositon of jackfruit(Artocarpus hetrophyllus) determined by HPLC–PDA-MS/MS. Plant Foods ForHuman Nutrition, doi:10.1007/S 11130-009r-r0111-6.

Favero, J., Corbeau, P., Nicolas, M., Benkirane, M., Trave, G., Dixon, J.F.P., Aucouturier,P., Rasheed, S., Liautard, J.P., Devaux, C., Dornand, J., 1993. Inhibition of humanimmunodeficiency virus infection by the lectin Jacalin and by a derived peptideshowing a sequence similarity wiyh gp120. European Journal of Immunology23, 179–185.

Fernando, M.R., Wickramasinghe, S.M.D.N., Thabrew, M.I., Ariyananda, P.L.,Karunanayake, E.H., 1991. Effect of Artocarpus heterophyllus and Asteracanthuslongifolia on glucose tolerance in normal human subjects and in maturity-onsetdiabetic patients. Journal of Ethnopharmacology 31, 277–282.

Ferrao, J.E.M., 1999. Fruticultura tropical: especies com frutos comestiveis, vol. I.Instituto de Investigacao Cientifica Tropical, Lisboa.

Gurjar, M.M., Khan, M.I., Gaikwad, S.M., 1998. �-Galactoside binding lectin fromArtocarpus hirsute: characterization of the sugar specificity and binding site.Biochimica et Biophysica Acta 1381, 256–264.

Gutierrez, R.M.P., Mitchell, S., Solis, R.V., 2008. Psidium guajava: a review of its tradi-tional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology117, 1–27.

Goncalves, J.L.S., Lopes, R.C., Oliveira, D.B., Costa, S.S., Miranda, M.M.F.S., Romanos,M.T.V., Santos, N.S.O., Wigg, M.D., 2005. In vitro antirotavirus activity of somemedicinal plants used in Brazil against diarrhoea. Journal of Ethnopharmacology99, 403–407.

Hagiwara, K., Collet-Cassart, D., Kobayashi, K., Vaerman, J., 1988. Jacalin: isolation,characterization and influence of various factors on its interaction with humanIgA1 as assessed by precipitation and latex agglutination. Molecular Immunol-ogy 25, 69–83.

Hakim, E.H., Achmad, S.A., Juliawaty, L.D., Makmur, L., Syah, Y.M., Aimi, N., Kitajima,M., Ghisalberti, E.L., 2006. Prenylated flavonoids and related compounds of theIndonesian Artocarpus (Moraceae). Journal of Natural Medicine 60, 161–184.

Heinrich, M., Heneka, B., Ankli, A., Rimpler, H., Sticher, O., Kostiza, T., 2005.Spasmolytic and antidiarrhoeal properties of the Yucatec Mayan medicinalplant Casimiroa tetrameria. The Journal of Pharmacy and Pharmacology 57,1081–1085.

Heyne, K., 1987. The Useful Indonesian Plants. Research and Development Agency,The Ministry of Forestry, Jakarta, pp. 659–703.

ICUC, 2003. International Centre for Underutilized Crops Report, Department of Civiland Environmental Engineering, University of Southhampton, SO 17 1BJ, UK.

Inbaraj, B.S., Sulochana, N., 2004. Carbonised jackfruit peel as an adsorbent for theremoval of Cd(II) from aqueous solution. Bioresource Technology 94, 49–52.

Jagtap, U.B., Panaskar, S.N., Bapat, V.A., 2010. Evaluation of antioxidant capacity andphenol content in jackfruit (Artocarpus heterophyllus Lam.) fruit pulp. Plant Foodsfor Human Nutrition, doi:10.1007/s11130-010r-r0155-7.

Jamil, S., Sirat, H.M., Jantan, I., Aimi, N., Kitajima, M., 2008. A new prenylated dihy-drochalcone from the leaves of Artocarpus lowii. Journal of Natural Medicine 62,321–324.

Jarret, F.M., 1959. Studies in Artocarpus and allied genera. III. A revision of Artocarpussubgenus Artocarpus. Journal of Arnold Arboretum 40, 1–298.

Jayasinghe, L., Balasooriya, B.A.I.S., Padmini, W.C., Hara, N., Fujimoto, Y., 2004. Ger-anyl chalcone derivatives with antifungal and radical scavenging properties
from the leaves of Artocarpus nobilis. Phytochemistry 65, 1287–1290.
Jayasinghe, L., Rupasinghe, G.K., Hara, N., Fujimoto, Y., 2006. Geranylated phe-nolic constituents from the fruits of Artocarpus nobilis. Phytochemistry 67,1353–1358.

Jensen, M.M., Wright, D.N., Robison, R.A., 1977. Microbiology for the Health Sciences.Prentice Hall, International Inc., London.

thnop

J

J

K

K

K

K

K

K

K

L

L

L

L

L

L

L

M

M

M

M

M

N

N

O

O

P

P

P


eyaprakash, A.A., Rani, P.G., Reddy, G.B., Bhanumathi, S., Betzel, C., Sekar, K., Surolia,A., Vijayan, M., 2002. Crystal; structure of the Jacalin-T-antigen complex andcomparative study of lectin-T-antigen complexes. Journal of Molecular Biology321, 637–645.

oshee, N., Bastola, D.R., Agrawal, V.P., Yadav, A.K., 2002. Lakoocha: a multipurposetree of warm climates. In: Janick, J., Whipkey, A. (Eds.), Trends in New Crops andNew Uses. ASHS Press, Alexandria, VA.

abir, S., 1995. The isolation and characterization of Jacalin [Artrocarpus heterophyl-lus (jackfruit) Lectin] based on its charge properties. International Journal ofBiochemistry and Cell Biology 27, 147–156.

abir, S., 1998. Jacalin: a jackfruit (Artocarpus heterophyllus) seed derived lectinof versatile applications in immunological research. Journal of ImmunologicalMethods 212, 193–211.

abir, S., Aebersold, R.A., Daar, A.S., 1993. Identification of a novel 4 kDaimmunoglobuliln-A-bindingpeptide obtained by the limited proteolysis ofJacalin. Biochimica et Biophysica Acta 1161, 194–200.

han, M.R., Omoloso, A.D., Kihara, M., 2003. Antibacterial activity of Artocarpus het-erophyllus. Fitoterapia 74, 501–505.

o, F.N., Cheng, Z.J., Lin, C.N., Teng, C.M., 1998. Scavenger and antioxidant propertiesof prenylflavones isolated from Artocarpus heterophyllus. Free Radical Biologyand Medicine 25, 160–168.

o, H.H., Lu, Y.H., Yang, S.Z., Won, S.J., Lin, C.N., 2005. Cytotoxic prenylflavonoidsfrom Artocarpus elasticus. Journal of Natural Products 68, 1692–1695.

oshihara, Y., Fujimoto, Y., Inone, H., 1998. A new 5-lipoxygenase selective inhibitorderived from Artocarpus communis strongly inhibits arachidonic acid inducedear edema. Biochemical Pharmacology 37, 2161–2165.

ansky, E.P., Paavilainen, H.M., Pawlus, A.D., Newman, R.A., 2008. Ficus spp. (fig):ethnobotany and potential as anticancer and anti-inflammatory agents. Journalof Ethnopharmacology 119, 195–213.

e Cointe, P., 1947. Amazonia Brasileira III. Arvires e plantas uteis. Companhia editoraNacional, Rio de Janeiro.

ikhitwitayawuid, K., Sritularak, B., 2001. A new dimeric stilbene with tyrosinaseinhibitory activity from Artocarpus gomezianus. Journal of Natural Products 64,1457–1459.

ikhitwitayawuid, K., Chaiwiriya, S., Sritularak, B., Lipipun, V., 2006. Antiherpeticflavones from the heartwood of Artocarpus gomezianus. Chemistry & Biodiversity3, 1138–1143.

ikhitwitayawuid, K., Sritularak, B., Benchanak, K., Lipipun, V., Mathew, J., Schi-naz, R.F., 2005. Phenolics with antiviral activity from Millettia erythrocalyx andArtocarpus lakoocha. Natural Product Research 19, 177–182.

im, S.B., Chua, C.T., Hashim, O.H., 1997. Isolation of a mannose-binding and IgE- andIgM-reactive lectin from the seeds of Artocarpus integer. Journal of Immunolog-ical Methods 209, 177–186.

in, K.W., Liu, C.H., Tu, H.Y., Ko, H.H., Wei, B.L., 2009. Antioxidant prenylflavonoidsfrom Artocarpus communis and Artocarpus elasticus. Food Chemistry 115,558–562.

ahanta, S.K., Krishnasastry, M.V., Surolia, A., 1990. Topography of the combiningregion of a Thomsen-Friendenreich-antigen specific lectin Jacalin (Artocarpusintegrifolia agglutinin). Biochemical Journal 265, 831–840.

ahanta, S.K., Sanker, S., Prasad Rao, N.V.S.A.V., Swamy, M.J., Surolia, A., 1992. Pri-mary structure of a Thomsen-Friendenreich-antigen specific lectin Jacalin [A.integrifolia (jackfruit) agglutinin]. Biochemical Journal 284, 95–101.

aia, J.G.S., Andrade, E.H.A., Zoghbi, M.G.B., 2004. Aroma volatiles from twofruit varieties of jackfruit (Artocarpus heterophyllus Lam.). Food Chemistry 85,195–197.

oreira, R.A., Castelo-Branco, C.C., Monteiro, A.C.O., Tavares, R.O., Beltramini, L.M.,1998. Isolation and partial characterization of a lectin from Artocarpus incisa L.seeds. Phytochemistry 47, 1183–1188.

usthapa, I., Juliawaty, L.D., Syah, Y.M., Hakim, E.H., Latip, J., Ghisalberti, E.L., 2009.An oxepinoflavone from Artocarpus elasticus with cytotoxic activity against P-388 cells. Archives of Pharmal Research 32, 191–194.

amdaung, U., Aroonrerk, N., Suksamrarn, S., Danwisetkanjana, K., Saenboonrueng,J., Arjchomphu, W., Suksamrarn, A., 2006. Bioactive constituents of the rootbark of Artocarpus rigidus subsp. rigidus. Chemical & Pharmaceutical Bulletin54, 1433–1436.

goc, D.D.T., Catrina, A.I., Lundberg, K., Harris, H.E., Ha, N.T., Anh, P.T., Lars-son, P., 2005. Inhibition by Artocarpus tonkinensis of the development ofcollagen-induced arthritis in rats. Scandinavian Journal of Immunology 61,234–241.

ng, B.T., Nazimah, S.A.H., Osman, A., Quek, S.Y., Voon, Y.Y., Hashim, D.M., Chew, P.M.,Kong, Y.W., 2006. Chemical and flavour changes in jackfruit (Artocarpus hetero-phyllus Lam.) cultivar J3 during ripening. Post Harvest Biology and Technology40, 279–286.

thman, Y., Subhadrabandhu, S., 1995. The Production of Economic Fruits in SouthEast Asia. Oxford University Press.

anunto-Castelo, A., Souza, M.A., Roque-Barreira, M.C., Silva, J.S., 2001. KM+, a lectinfrom Artocarpus integrifolia, induces IL-12 p40 production by macrophages andswitches from type 2 to type 1 cell mediated immunity against Leishmaniamajor antigens, resulting in BALB/c mice resistant to infection. Glycobiology 11,1035–1042.

ereira, M.E.A., Loures, M.A., Villalta, F., Andrade, A.B., 1980. Lectin receptorsas a markers for Trypanosoma cruzi. Journal of Experimental Medicine 152,1375–1392.

ereira-da-Silva, Moreno, A.N., Marques, F., Oliver, C., Jamur, M.C., Panunto-Castelo,A., Roque-Barreira, M.C., 2006. Neutrophil activation induced by the lectin Km+involves binding to CXR2. Biochimica et Biophysica Acta 1760, 86–94.

harmacology 129 (2010) 142–166 165

Perry, L.M., 1980. Medicinal Plants of East and South East Asia Attributed Propertiesand Uses. MIT Press, Cambridge.

Peumans, W.J., Hause, B., Van Damme, E.J., 2000. The galactose binding and mannosebinding Jacalin-related lectins are located in different sub cellular compartment.FEBS Letter 477, 186–192.

Pilatte, Y., Hammer, C.H., Frank, M.M., Fries, L.F., 1989. A new simplified proce-dure for C1 inhibitor purification. A novel use for jacalin-agarose. Journal ofImmunological methods 120, 37–43.

Pineau, N., Aucouturier, P., Brugier, J.C., Prendhomme, J.L., 1990. Jacalin: a lectin mito-genic for human CD4 T-lymphocytes. Clinical and Experimental Immunology 80,420–425.

Pitaksuteepong, T., Somsiri, A., Waranuch, N., 2007. Targeted transfollicular deliv-ery of artocarpin extracts from Artocarpus incisus by means of microparticles.European Journal of Pharmaceutics and Biopharmaceutics 67, 639–645.

Pratap, J.V., Jeyaprakash, A.A., Geetha Rani, P., Sekar, K., Surolia, A., Vijayan, M., 2002.Crystal structures of artocarpin, a Moraceae lectin with mannose specificity,and its complex with methyl-�-d-mannose. Implications to the generation ofcarbohydrate specificity. Journal of Molecular Biology 317, 237–247.

Rahman, M.A., Karsani, S.A., Othaman, I., Rahman, P.S.A., Hashim, O.H., 2002. Galac-tose binding lectin from the seeds of champedak (Artocarpus integer): sequencesof its subunits and interactions with human serum o-glycosylated glycoproteins.Biochemical and Biophysical Research Communications 295, 1007–1013.

Ray, S., Chatterjee, B.P., 1989. Purification of Ant-Egg glycoprotein and its interactionwith Jacalin. Carbohydrate Research 191, 305–314.

Rosa, J.C., Garrat, R., Beltramini, L., Resing, K., Roque-Barreira, M.C., Greene, L.J.,1999. KM+, a mannose-binding lectin from Artocarpus integrifolia: amino acidsequence, predicted tertiary structure, carbohydrate recognition and analysis ofthe beta-prism fold. Protein Science 8, 13–24.

Rudiger, H., Gabius, H.J., 2001. Plant lectins: occurrence, biochemistry, functions andapplications. Glycoconjugate Journal 18, 189–613.

Ruffet, E., Paquet, N., Frutiger, S., Hughes, G., Jaton, J.C., 1992. Structural and electronmicroscopic studies of Jacalin from jackfruit (Artocarpus integrifolia) show thatthis lectin is a 65 kDa tetramer. Biochemical Journal 286, 131–134.

Rujinirum, C., Phinyocheep, P., Prachyabrued, W., Laemsak, N., 2005. Chemical treat-ment of wood for musical instruments. Part I. Acoustically important propertiesof wood for the Ranad (Thai traditional xylophone). Wood Science Technology39, 77–85.

Sahasrabuddhe, A.A., Gaikwad, S.M., Krishnasastry, M.V., Islam Khan, M., 2004.Studies on recombinant single chain Jacalin lectin reveal reduced affinity forsaccharides despite normal folding like native Jacalin. Protein Science 13,3264–3273.

Sahasrabuddhe, A.A., Ahmed, N., Krishnasastry, M.V., 2006. Stress induced phos-phorylation of caveolin-1 and p38, and down regulation of EGFr and ERK bythe dietary lectin Jacalin in two human carcinoma cell lines. Cell Stress andChaperones 11, 135–147.

Salguero, C.P., 2003. A Thai Herbal Traditional Recipes for Health and Harmony.Findhorn Press, Scotland, pp. 119.

Sankarnarayanan, R., Sekar, K., Banerjee, R., Sharma, V., Surolia, A., Vijayan, M., 1996.A novel mode of carbohydrate recognition in Jacalin, a Moraceae plant lectinwith a �-prism fold. Nature Structural Biology 3, 596–603.

Santos-de-Olievira, R., Dias-Baruffi, M., Thomaz, S.M., Beltramini, L.M., Roque-Barreira, M.C., 1994. A neutrophil migration inducing lectin from Artocarpusintegrifolia. Journal of Immunology 153, 1798–1807.

Saowakon, N., Tansatit, T., Wanichanon, C., Chaakul, W., Reutrakul, V., Sobhan, P.,2009. Fasciola gigantica: anthelmintic effect of the aqueous extract of Artocarpuslakoocha. Experimental Parasitology 122, 289–298.

Sastry, M.V., Banarjee, P., Patanjali, S.R., Swamy, M.J., Swarnalatha, G.V., Surolia,A., 1986. Analysis of saccharide binding to Artocarpus integrifolia lectin revealsspecific recognition of T-antigen (�-d-Gal(1–3)d-GalNAc). Journal of BiologicalChemistry 261, 11726–11733.

Sato, M., Fujiwara, S., Tsuchiya, H., Fujii, T., Iimuna, M., Tosa, H., Ohkawa, Y.,1996. Flavones with antibacterial activity against cariogenic bacteria. Journalof Ethnopharmacology 54, 171–176.

Saxon, A., Tsui, F., Martinez-Maza, O., 1987. Jacalin, an IgA-binding lectin, inhibitsdifferentiation of human B cells by both a direct effect and by activating T-suppressor cells. Cell Immunity 104, 134–141.

Seo, E.K., Lee, D., Shin, Y.G., Chai, H.B., Navarro, H.A., Kardono, L.B.S., Rahman, I.,Cordell, G.A., Farnsworth, N.R., Pezzuto, J.M., Kinghorn, A.D., Wani, M.C., Wall,M.E., 2003. Bioactive prenylated flavonoids from the stem bark of Artocarpuskemando. Archives of Pharmalogical Research 26, 124–127.

Shimizu, K., Fukuda, M., Kondo, R., Sakai, K., 2000. The 5-�-reductase inhibitory com-ponents from heartwood of Artocarpus incisus: structure–activity investigations.Planta Medica 66, 16–19.

Singh, S., Krishnamurthy, S., Katyal, S., 1963. Fruit Culture in India. ACAR, New Delhi.Soong, Y.Y., Barlow, P.J., 2004. Antioxidant activity and phenolic content of selected

fruit seeds. Food Chemistry 88, 411–417.Soubir, T., 2007. Antioxidant activities of some local bangladeshi fruits (Artocar-

pus heterophyllus, Annona squamosa, Terminalia bellirica, Syzygium samarangense,Averrhoa carambola and Olea europa). Chinese Journal of Biotechnology 23,257–261.

Suhartati, T., Achmad, S.A., Aimi, N., Hakim, E.H., Kitajima, M., Takayama, H., Takeya,K., 2001. Artoindonesianin L, a new prenylated flavone with cytotoxicity activityfrom Artocarpus rotunda. Fitoterapia 72, 912–918.

Suhartati, T., Yandri, Hadi, S., 2008. The bioactivity test of artonin E from thebark of Artocarpus rigida Blume. European Journal of Scientific Research 23,330–337.

1 thnop

S

S

T

T

T

T

U

V

Young, M.N., Johnston, R.A.Z., Szabo, A.G., Watson, D.C., 1989. Homology of the d-galactose specific lectins from Artocarpus integrifolia and Maclura pomifera andthe role of an unusual small polypeptide subunit. Archives of Biochemistry and


yah, Y.M., Achmad, S.A., Ghisalberti, E.L., Hakim, E.H., Mujahidin, D., 2004. Two newcytotoxic isoprenylated flavones, artoindonesianin U and V from heartwood ofA. chempeden. Fitoterapia 75, 134–140.

yah, Y.M., Juliawaty, L.D., Achmad, S.A., Hakim, E.H., Ghisalberti, E.L., 2006. Cytotoxicprenylated flavones from Artocarpus chempeden. Journal of Natural Medicine 60,308–312.

amma, S.M.L., Kalyanaraman, V.S., Pahwa, S., Dominguez, P., Modesto, R.R., 2003.The lectin Jacalin induces phosphorylation of ERK and JNK in CD4+ T cells. Journalof Leukocyte Biology 73, 682–688.

engamnuay, P., Pengrungruangwong, K., Pheansri, I., Likhitwitayawuid, K., 2006.Artocarpus lakoocha heartwood extract as a novel cosmetic ingredient: eval-uation of the in vitro anti-tyrosinase and in vivo skin whitening activities.International Journal of Cosmetic Science 28, 269–276.

oda, S., Shirataki, Y., 2006. Inhibitory effect of prenylated flavonoid in Euchrestajaponica and Artocarpus heterophyllus on lipid peroxidation by interaction ofhemoglobin and hydrogen peroxide. Pharmaceutical Biology 44, 271–273.

rindade, M.B., Lopes, J.L.S., Costa, A.S., Moreira, A.C.M., Moreira, R.A., Oliva, M.L.V.,Beltramini, L.M., 2006. Structural characterization of novel chitin binding lectinsfrom the genus Artocarpus and their antifungal activity. Biochimica et BiophysicaActa 1764, 146–152.

ddin, M.T., Rukanuzzaman, Md., Khan, Md.M.R., Islam, Md.A., 2009. Adsorption ofmethylene blue from aqueous solution by jackfruit (Artocarpus heterophyllus)leaf powder: a fixed-bed column study. Journal of Environmental Management90, 3443–3450.

erheij, E.W.M., Coronel, R.E., 1992. Plant Resources of South-East Asia No. 2. EdibleFruits and Nut. Prosea, Bogor Indonesia.

harmacology 129 (2010) 142–166

Verpoorte, R., Choi, Y.H., Kim, H.K., 2005. Ethnopharmacology and systems biology:a perfect holistic match. Journal of Ethnopharmacology 100, 53–56.

Wang, Y., Deng, T., Lin, L., Pan, Y., Zheng, X., 2006. Bioassay guided isolationof antiatherosclerotic phytochemicals from Artocarpus altilis. PhytotherapyResearch 20, 1052–1055.

Wei, B.L., Weng, J.R., Chiu, P.H., Hung, C.F., Wang, J.P., Lin, C.N., 2005. Antiinflamma-tory flavonoids from Artocarpus heterophyllus and Artocarpus communis. Journalof Agricultural and Food Chemistry 53, 3867–3871.

Weng, J.R., Chan, S.C., Lu, Y.H., Lin, H.C., Ko, H.H., Lin, C.N., 2006. Antiplateletprenylflavonoids from Artocarpus communis. Phytochemistry 67, 824–829.

Widyawaruyanti, A., Subehan, Kalauni, S.K., Awale, S., Nindatu, M., Zaini, N.C.,Syafruddin, D., Asih, P.B.S., Tezuka, Y., Kadota, S., 2007. New prenylated flavonesfrom Arocarpus champeden and their antimalarial activity in vitro. Jouranl ofNatural Medicine 61, 410–413.

Wongkham, S., Wongkham, C., Boonsiri, P., Simasathiansophon, S., Trisonthi, C., Ati-sook, K., 1995. Isolectins from seeds of Artocarpus lakoocha. Phytochemistry 40,1331–1334.

Biophysics 270, 596–603.Young, M.N., Johnston, R.A.Z., Watson, D.C., 1991. The amino acid sequences of Jacalin

and the Maclura pomifera agglutinin. FEBS Letters 282, 382.

artocarpus: a review of its traditional uses, phytochemistry and … · 2014-08-13 · journal of...

Documents