common traditional chinese medicinal herbs for dysmenorrhea

CHINESE HERBS FOR DYSMENORRHEA 819

Copyright © 2006 John Wiley & Sons, Ltd. Phytother. Res. 20, 819–824 (2006)DOI: 10.1002/ptr

Copyright © 2006 John Wiley & Sons, Ltd.

PHYTOTHERAPY RESEARCHPhytother. Res. 20, 819–824 (2006)Published online 11 July 2006 in Wiley InterScience(www.interscience.wiley.com) DOI: 10.1002/ptr.1905

REVIEW ARTICLECommon Traditional Chinese Medicinal Herbsfor Dysmenorrhea

Wei Jia1,2*, Xiaorong Wang1, Desheng Xu2, Aihua Zhao1 and Yongyu Zhang2

1The School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China2Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai,China

Dysmenorrhea is painful menstrual cramps, which negatively impacts the quality of life of those diagnosed.The paper reviews traditional Chinese medicine’s treatment of dysmenorrhea through the use of combination-herbal-formula therapeutics. These herbal treatments are effective for dysmenorrhea with minimal sideeffects. Pharmacological studies suggest Chinese herbal dysmenorrhea therapies likely decrease prostaglandinlevels, modulate nitric oxide, increase plasma βββββ -endorphin (βββββ -EP) levels, block calcium-channels and improvemicrocirculation. Conventional therapy for dysmenorrhea, which usually includes non-steroidal antiinflammatorydrugs (NSAIDs), provides symptomatic relief but has increasing adverse effects with long-term use. Therefore,Chinese herbal medicines, including simple herbal and combination formulas, are perhaps the ideal therapeu-tics of choice. Copyright © 2006 John Wiley & Sons, Ltd.

Keywords: dysmenorrhea; traditional Chinese medicine; Chinese herbs; combined formulas.

Received 3 February 2006Accepted 2 March 2006

with clinically diagnosed dysmenorrhea, compared withcontrols (Ostad et al., 2001). Vasopressin increasespremenstrually and was found in non-pregnant womento be five times more effective on uterine activity thanthat of oxytocin (Deligeoroglou, 2000; Dawood, 1990).As a result, dysmenorrhea is caused by uterine musclehypercontractility, subsequent blood flow reduction andconcurrent uterine ischemia (Akerlund, 1979). Corre-spondingly, there is a significant reduction in uterineblood flow associated with the time of maximal pain(Khamis et al., 2003). Studies suggest uterine diameterand endometrial thickness are related to severe pri-mary dysmenorrhea (Dmitrovic, 2004).

Current dysmenorrhea therapies include non-steroidal antiinflammatory drugs (NSAIDs), combinedwith oral contraceptives, beta-blockers, vitamin B1,vitamin B6, magnesium and calcium channel-blockers(Pei et al., 2001; Milsom et al., 2002; Vercellini, 2003;Hendrix and Alexander, 2002; Wilson and Murphy,2001).

NSAIDs relieve dysmenorrheal effects by inhibitingcyclooxygenase production, a component of the arachi-donic acid cascade (Ostad et al., 2001). However, themajority of NSAIDs have adverse long-term effectsinvolving disorders of the liver, kidney and digestivesystems. In addition, acute liver injury and acute renalfailure have also been reported (Garcia-Rodriguezet al., 1994; Perez-Gutthann et al., 1996). Whileoral contraceptives can be an effective dysmenorrhealtreatment, by reducing PGs, inhibiting endocardiumproliferation and reducing blood flow, this treatmentmay not be suitable for all women, especially thosepursuing pregnancy (Hendrix and Alexander, 2002;Vercellini et al., 2003). Beta (β)-blockers, vitamin B1,B6, magnesium, calcium channel-blockers and psycho-therapeutic method (Wilson and Murphy, 2001) areall recommended as potential treatments for primary

INTRODUCTION

Dysmenorrhea causes severe pain which negativelyimpacts on a woman’s quality of life. Dysmenorrheais classified as either primary or secondary. Primarydysmenorrhea results from elevated prostaglandins(PGs), has no visible pelvic disease and produces uterineischemia and pain. Secondary dysmenorrhea presentswith both high PG levels and uterine pathologiessuch as endometriosis and pelvic inflammation (Harel,2002; Coll Capdevila, 1997). Primary and secondary dys-menorrhea are both common gynecological complaints,with 30–60% of reproductive age women reporting painduring menstruation. Of those reporting pain, 13.5%suffer pain too severe to maintain their normal life orjob during 1–3 days of the menstrual cycle (Liao, 2004).Though the mechanisms of primary dysmemorrheaoccurring most frequently in teens have not beenelucidated, prostaglandin (PGs), leukotrienes (LTs)and vasopressin are likely involved. Before menstrua-tion but after progesterone withdrawal, a PG and LTcascade is initiated in the uterus. The inflammatoryresponse, which is mediated by these PGs and LTs,produces abdominal pain, cramps, headaches and othersystemic discomfort exhibited as facial paleness, coldsweats, nausea, vomiting and bloating (Deligeoroglou,2000). Furthermore, PG plasma and vasopressin levelsare elevated (Ostad et al., 2001; Dawood, 1990). UterinePG production is up to seven times greater in women

* Correspondence to: Dr W. Jia, School of Pharmacy, Shanghai Jiao TongUniversity, Shanghai 200240, China.E-mail: [email protected]/grant sponsor: Shanghai Leading Academic Discipline Project;contract/grant number: T0301.


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dysmenorrhea. Cervical dilatation and laparoscopicresection of the uterosacral ligaments are used inpatients with severe dysmenorrhea (Andersson, 1988;Vercellini, 2003). In China, traditional Chinese medi-cine and herbs are considered as an alternative treat-ment for dysmenorrhea. This paper reviews traditionalChinese medical herbal therapies used for the treat-ment of dysmenorrhea.

TRADITIONAL CHINESE MEDICINE (TCM)TREATMENT OF DYSMENORRHEA

Traditional Chinese medicine (TCM) differs from West-ern medicine not only in theory and diagnosis but alsoin interpretation of both normal physiological functionand pathological changes in the human body. In a word,TCM emphasizes the harmony between the humanbody and the illness that is caused by the ‘Yin’ and‘Yang’ imbalance resulting from invasion of exogenousfactors. Dysmenorrhea was first documented in GinGui Yao Lu by Zhongjing Zhang of Donghan dynasty(A.D.196). In TCM, the main cause of dysmenorrheais qi stasis in the liver by the invasion of six exo-genous pathogenic factors. Qi stasis concurrently blocksthe blood flow, which further forms blood stasis andlumps. Menstrual pain resulting from qi is due tostagnated and retained blood. Blood deficiency andcoldness in the whole human body are two additionalcauses of dysmenorrhea. Thus, dysmenorrhea can bedivided into qi stasis, blood stasis, or blood deficiencytypes according to different situations. The essenceof the TCM theory for treating nonspecific disorders,such as dysmenorrhea, involves eliminating the intrinsiccauses.

Treatment of the qi stasis type of dysmenorrhea, aimsto promote fluid qi movement. To promote qi andblood flow, traditional medicinal herbs such as Cyperusrotundus, Foeniculum vulgare, Angelicae sinensis andLigusticum chuanxiong, are often recommended. In theblood stasis type, Angelicae sinensis, Ligusticum chuan-xiong, Paeonia lactiflora and Typha angustifolia arerecommended to break blood stasis and resolve lumps,thereby activating blood circulation. Angelicae sinensis,Codonopsis pilosula, Rehmannia glutinosa, Paeonia veit-chii, Paeonia lactiflora and Polygoum multiflorum herbsare prescribed for the blood deficiency type to preventasthenia and strengthen the body to withstand patho-genic invasion.

Approximately 136 Chinese medicinal herbs areprescribed in the TCM treatment of dysmenorrhea.According to the literature, the 30 herbs listed belowhave been used most frequently by clinicians (Dong,2003) (Table 1).

Combined prescriptions, according to the compara-bility principle in TCM, are often used to streng-then herbal effectiveness and to mitigate toxic effects.Hundreds of combined formulas to treat symptomaticdysmenorrhea have been documented in various his-torical Material Medica and contemporary journals.Currently 13 unique prescriptions for treating dysmenor-rhea are approved by the Chinese State Food and DrugAdministration (SFDA). The most frequently used,compositions and usage interpretations of TCM arelisted in Table 2.

Table 1. 30 herbs used most frequently in TCM for dysmenorrhea

Pharmacopea name Binomial name

Caulis Sargentodoxae Sargentodoxa cuneataCortex Cinnamomi Cassiae Cinnamomum cassiaCortex Moutan Paeonia suffruticosaFaeces Trogopterorum Trogopterus xanthipes

or Pteromys volansFlos Carthami Carthamus tinctoriusFlos Rosae Chinensis Rosa chinensisFructus Akebiae Akebia quinataFructus Foeniculi Foeniculum vulgareFructus Jujubae Ziziphus jujubeHerba Leonuri and Leonurus heterophyllusFructus LeonuriHerba Selaginellae Selaginella tamariscinaHerba Lycopi Lycopus iucidusHerba Verbenae Verbena officinalisLignum Sappan Lignum sappanPollen Typhae Typha angustifoliaRadix Angelicae Sinensis Angelicae sinensisRadix Astragali Astragalus membranaceusRadix Curcumae Aromaticae Curcuma aromaticaRadix Linderae Lindera strychnifoliaRadix Paeoniae Alba and Paeonia veitchii andRadix Paeoniae Rubra Paeoni lactifloraRadix Rehmanniae Rehmannia glutinosaRadix Salviae Miltiorrhizae Salvia miltiorrhizaRhizima Chuanxiong Ligusticum chuanxiongRhizoma Corydalis Corydalis yanhusuoRhizoma Curcumae Longae Curcuma longaRhizoma Cyperi Cyperus rotundusSemen Persicae Prunus persicaSemen Vaccariae Vaccaria segetalis

PHARMACOLOGICAL STUDIES ANDCLINICAL SURVEY OF 5 WIDELY USED TCMHERBAL TREATMENTS IN DYSMENORRHEA

Current research suggests several mechanisms by whichTCM herbal treatments effectively treat dysmenorrheaincluding: modulation of PGs levels, nitric oxide reduc-tion, calcium channel inhibition, β-endorphin upregula-tion and microcirculation regulation (Wei and Wu, 2000;Ma et al., 2004; Liu et al., 2004a; Peng et al., 2001; Liuand Jiang, 2000). Combined herbal formulas would beexpected to incorporate several mechanisms to treatsymptoms of dysmenorrhea. The following section de-scribes the potential mode of action of five frequentlyused herbal prescriptions for dysmenorrheal treatment.

Aifu Nuangong pill. Aifu Nuangong pills, administeredgastrointestinally at three doses of 6 × 10−5, 12 × 10−5

and 24 × 10−5 g/kg on an oxytocin-induced rat model,significantly (p < 0.01) decreased the frequency of writh-ing in rats observed when compared with a positivecontrol group (morphine solution at dose of 6 × 10−4 g/mL) (Wang et al., 2003). Subsequently, the average β-EP concentrations were 169.3 and 176.5 ng/L in themedian and highest dose groups. These data were con-sistent with that of the blank group (150.1 ng/L). Theabove results implied that increasing the blood serumβ-EP concentration is likely to contribute to the abilityof the Aifu Nuangong pill to alleviate pain, in additionto its direct influence on uterine smooth muscular con-traction. Further, Radix Angelicae Sinensis (Angelicae



Table 2. Combination formulas and their traditional use in dysmenorrheal treatments

Chinese name

Aifu Nuangong pill

Bazhen decoctionDanggui Shaoyao powder

Gexia Zhuyu decoction

Jiuqi Niantong pill

Peikun pillShaofu Zhuyu decoction

Shaoyao Gancao decoction

Tiaogan decoction

Composition

Folium ArtemisiaeRhizoma CyperiFructus EvodiaeCortex Cinnamomi CassiaeRadix Angelicae SinensisRhizima Chuanxiong RadixPaeoniae AlbaRadix RehmanniaeRadix ScutellariaeRadix Dipsaci

Radix CodonopsisRhizoma AtractylodisMarcroephalae PoriaRadix Angelicae SinensisRadix Paeoniae AlbaRhizoma Rehmanniae PraeparataRadix GlycyrrhizaeRadix AstragaliRadix AucklaneliaeRadix Angelicae SinensisRadix Paeoniae RubraRhizima ChuanxiongRhizima AtractylodisMacrocephlae PoriaRhizoma Alismatis

Radix Angelicae SinensisFaeces TrogopterorumRhizima ChuanxiongRadix LinderaeRadix Paeoniae RubraRhizoma Corydalis YanhusuoRhizoma Cyperietc.

Rhizoma CyperRadix AucklandiaeRhizoma Alpiniae officinarumRhizoma CorydalisPericarpium Citri ReticulataeRadix curcumaeRhizoma CurcumaeSemen ArecaeRadix GlycyrrhizaeFaeces Trogopterorum

Radix Angelicae SinensisRhizoma Rehmanniae PraeparataRadix Astragalietc.Radix Angelicae SinensisPollen TyphaeFaeces TrogopterorumRadix Paeoniae RubraFructus FoeniculiRhizoma CorydalisCommiphora MyrrhaRhizima ChuanxiongCinnamomum ZeylanicumRhizoma Zingiberis Preparara

Radix Paeoniae AlbaRadix Glycyrrhizae

Rhizoma DioscoreaeColla Corii AsiniRadix Angelicae SinensisRadix Paeoniae AlbaFructus Coni

Chinese traditional use

Regulating qi and supplementing blood to warmuterine for menoxenia and dysmenorrhea

Strengthening the spleen and nourishing qi,invigorating blood and stopping bleedingApplicable to the treatment of cold coagulationand blood stasis

Smoothing the liver to regulate qi and resolvingstasis to stop pain

Regulating qi and activating blood to relieve pain

Nourishing blood and regulating the liver, replenishingthe kidney and enriching essenceDissolving the stagnation in blood vessels to promoteblood circulation and dispersing coldness for relievingpain

Treatment of dysmenorrhea with cold coagulation andblood stasis

Nourishing blood and regulating the liver, replenishingthe kidney and enriching essence


822 W. JIA ET AL.

Table 2. (Continued)

Chinese name

Tongjing pill

Xuefu Zhuyu decoction

Yueyueshu powder

Yuanhu Zhitong tablet

Composition

Radix Morindae OfficinalisFructus LyciiRhizoma CyperiRhizoma Rehmanniae PraeparataSemen Astragali ComplanatiRadix Glycyrrhizae

Radix Angelicae SinensisRadix Paeoniae AlbaRhizima ChuanxiongRhizoma Rehmanniae PraeparataRadix Aucklaneliaeetc.

Radix Angelicae SinensisRhizima ChuanxiongRadix Paeoniae RubraFlos CarthamiSemen PersicaeRadix CyathulaeRhizoma CyperiPericarpium CitriReticulatae VirideFructus AurantiiRadix Aucklaneliae

Rhizoma Corydalis YanhusuoFaeces TrogopterorumRadix GlycyrrhizaeRadix Salviae MiltiorrhizaeCortex Cinnamomi CassiaeFlos CarthamiFaeces TrogopterorumRhizoma SparganiiRhizoma CurcumaeRhizoma Corydalis YanhusuoRadix Angelicae SinensisRadix AucklaneliaeRhizoma Corydalis Yanhusuo

Radix Angelicae Dahuricae

Chinese traditional use

Warming human body to disperse cold coagulationand blood stasis resulting in coldness

Smoothing the liver to regulate qi and resolving stasisto stop pain

Applicable to the treatment of cold coagulation andblood stasis

Applicable to the treatment of dysmenorrhea due to‘qi’ stagnation and blood stasis

in mice with oxytocin-induced dysmenorrhea. At dosesof 1 and 2 g/kg in rats, the Shaofu Zhuyu Pill alsoalleviated uterine contractions (Wu, 2003). Furtherstudies verified the usefulness of the Shaofu Zhuyupill for chronic inflammation, uterine hyperplasia,improving perimetrium microcirculation, and decreas-ing whole blood viscosity in animals. In 126 patientswith dysmenorrhea treated with the Shaofu Zhuyupill for 4 days, 102 showed significantly reducedlower abdominal pain (Zhou et al., 2002). Thus, theShaofu Zhuyu pill relieves pain from uterine smoothmuscle contractions, and decreases blood viscosity andinflammation.

Peikun capsule. Isolated uterine muscle preparationsfrom female rats and dysmenorrheal mouse models,induced by diethylstilbestrol and oxytocin, were usedto evaluate the effectiveness of the Peikun capsule onuterine contractile force, frequency and degree ofactivity. When graded concentrations (from 0.1, 0.2, 0.4,0.8, 1.6 g/L) were added to isolated uterine muscle,contractile forces were inhibited by 11.6–65.7%, fre-quencies were reduced by 28.2–60.2%, and activities

sinensis), a component of the Aifu Nuangong pill,relaxes uterine smooth muscle and increases bloodcirculation. Ligustilide, isolated from Radix AngelicaeSinensis, is used to treat dysmenorrhea, because it canrelax the contraction of uterine smooth muscle (Liuet al., 2004a, 2004b). Lastly, 95% of dysmenorrheapatients in the Shenzhen traditional Chinese hospitalof Guanzhou traditional Chinese Medical College, whowere treated with the modified Aifu Nuangong formula,recovered (Wang et al., 2003).

Jiuqi Niantong capsule. Peng Zhipei demonstrated thatthe Jiuqi Niantong capsule, used to treat dysmenorrhea,increased β-EP, NO and ET-1 in blood plasma ofuterine tissue (Peng et al., 1999b). In mice with oxytocin-induced dysmenorrhea, the Jiuqi Niantong pill produceda statistically significant reduction in latent periods andwrithing times, a proxy for pain, compared with thecontrol group (treated with distilled water) (Peng et al.,1999a).

Shaofu Zhuyu pill. The Shaofu Zhuyu pill at doses of1.8 and 3.6 g/kg significantly extended the latent period



were reduced by 36.6–84.6% with IC50 of 0.69 g/L,0.83 g/L and 0.23 g/L, respectively in vitro (Cao et al.,2002). In addition, the writhing of times of dysmenor-rhea mice were significantly reduced at doses of 2.0and 5.0 g/kg. The results showed that Peikun capsulecan effectively inhibit uterine contraction, therebyalleviating pain from dysmenorrhea. In another investi-gation, the Peikun capsule reduced oxygen consump-tion, raised the pain threshold and lowered bodytemperature (Cao et al., 2001). This combinationformula exerts a holistic effect in the treatment ofdysmenorrhea by nourishing yin and supplementingthe kidney.

Yueyueshu powder. Zhao Shumei reported treatingprimary and secondary dysmenorrhea in 97 patientswith either Yueyueshu powder or the PG blocker,indomethacin, at the Baotou Medical College Hospital.Patients received 10 g of Yueyueshu powder twice dailyor 25 mg indomethacin three times daily. The efficacyof Yueyueshu powder was 77.8% and 69.1% in pri-mary and secondary dysmenorrhea, respectively, whilethe efficacy of indomethacin was 76.1% and 36.1%for primary and secondary dysmenorrhea, respectively(Zhao and Hong, 1996). In traditional Chinese medi-cine, this formula can dispense cold coagulation anddissolve blood stasis to ‘warm up’ the body and pro-mote blood flow, which could be a multicomponents-to-multitargets approach, rather than a singlePG-blocking mechanism.

CONCLUSION

Dysmenorrhea is one of the most common gynecologicalailments directly influencing a woman’s quality of life.

Non-steroidal antiinflammatory drugs (NSAIDs) areusually employed rapidly to reduce the symptomsof dysmenorrhea. However, long term treatment withNSAIDs can have severe side effects. TraditionalChinese medicine and medicinal herbs have been usedto protect and treat conventional chronic diseasesthroughout China’s long history. In other words, theeffectiveness of TCM herbs was first verified in patientsand then contemporary scientific technologies havegradually validated their effectiveness.

Since Chinese herbal treatments (simple or combi-natorial) are effective and often have reduced sideeffects, medicinal herbs are considered to be an alter-native to conventional remedies for many diseases.Herbal prescriptions, containing unique herbal formu-lations, effectively treat dysmenorrhea by dispellingqi stasis, dissolving blood stasis and dissociating lumpsin blood vessels, thereby promoting qi and blood flow.Herbal formulations improve the benefits of eachconstituent while minimizing the toxic effects of others,thereby promoting the best therapeutic benefit withminimal side-effects. In fact, most herbs can eliminateintrinsic causes of disease. In TCM, qi and stasis result-ing from splenic deficiency can be effectively treated bysupplementing with splenic herbs, which directly dispelqi and dissolve stagnation in the blood vessels.

The precise mechanisms of TCM herbal action needto be further investigated via phytochemical analysis,to identify the active compounds from herbs and herbalformulations and meet the growing demands for herbalmedicine and phytotherapies in the coming decades.

Acknowledgement

This study was financially supported by Shanghai Leading AcademicDiscipline Project, Project Number, T0301.

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common traditional chinese medicinal herbs for dysmenorrhea

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