angelica sinensis (dong quai)

8/12/2019 Angelica Sinensis (Dong Quai)

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ngelica sinensi

Angelica sinensis(Dong quai)DescriptionAngelica sinensis (commonlyknown as dong quai) isa fragrant, peren-nial herb found in mainland C hina. Japan,and K orea. Other common names for dongquai include Chinese Angelica, danggui(Chinese), toki (Japanese), tanggwi (Ko-rean), and kinesisk kvan (Danish). A member of the Um belliferae family, Angelica produces w hite flowersthat bloom in um brella-like clusters in June-July. A typical plant grows to a height of approxim ately six feet(two meters). The dried rootisvaluedfor its therapeutic properties. Its flavoris a distinet blendofbitter,sweet, and pungent, and its overall effeet iswarminginnature. Chinese herbalists have used Angelicaforthousands of years to strengthen heart, lung, and liver meridians, as well as lubricate the bowe l.Itis con sid-eredablood tonic, and has been used by generationsofwomen for health eoncerns such as menstrual painand regulating the menstrual cycle.

Active ConstituentsDong quai root contains 0.4-0.7 percent volatile oil, the keycomponents of which are n-butylidenephthalide. ligustilide. n-butylphthalide. ferulic acid, nicotinic acid, and succinic acid.'"* Signifi-cant amountsof vitamin A and carotenoids (0.675%). vitamin B12 (0.25-0.40 meg/100 g), vitamin E. ascor-bic acid, folinic acid, biotin. various phytosterols (e.g.. beta-sitosterol). ealcium, magnesium, andotheressential macrominerals are also found indong quai root.' ^^ Other constituents include n-valerophen one-O-carbo\ylic acid, delta-2.4-dihydrophthalic anhydride, uracil. adenine, carvacrol. safrole, isosafrole, ses-quiterpenes, beta-cadinene, n-dodeeanol. n-tetiadeeanol. palmitic acid, angelic acid, myristic acid, sucrose(40%).andapolysaccharide withamolecular weightofapproximately 3.000.''^Natural coumarin derivatives have been attributed to dong quai. but reports differ regarding whichonesaretruly p resent. The coumarin derivatives include angelo l, angelicone, bergapten. oxypeu eedanin,osthole, psoralen, and 7-desmethylsuberosin.' *'

M echanism s of ActionDueto itsvaried con stituents, several pharm acological actionsmay beattributed to dong quai.Such characteristics include anticoagulation^ and antiplatelet activity,' as well as hematop oiesis/ immunesupport.'^'' and uterine tonicity.'-"^"'

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Anticoagulant ActivityCoumarins and coumarin derivatives,

natural anticoagulantsinAngelica spp., have beenassociated with both the bioactivity and toxicityofthe plants: however.A. sinensiscontains a lowercoumarin content compared to other closely re-lated species.^Antiplatelet Action

Ferulic acid, oneoi the constituentsofdong quai, can inhibit the polymerization of plate-lets in blood circulation. It retards platelet releaseof 5-hydroxytryptamine (5-HT) and adenosinediphosphate (ADP).' Both ferulic acid andanaqueous extractofdong quai were found toin-hibit platelet aggregation and serotonin relea.se.-Immune Support and Hematopoiesis

Lymphocyte proliferation assays indicatedong quai consis tently exer ts aninimunostim ulatory effe ct/' ' A high m olecularweight poiysaccharide found in dong quai has dem-onstrated imm unostimulating activity and a bloodtonifying effect by inducing hematopoiesis in thebone marrow. This is accomplished, in part, by ei-ther direct or indirect stimulation of macrophages.fibroblasts. erythrocytes. granulocytes. and lym-phocytes, and can induce an increased secretion ofhuman growth factors from muscle tissue.^

Hematopoiesis is further supported by thepresenceofsignificant amoun tsofvitamin B I2.folinic acid, and biotin in dong quai.^Antijibrotic Action

A mixtureofdong quai and A stragalusdemonstrated antifibrotic activity in a recent ani-mal study. Rat models with chronic puromycin-induced nephrosis were treated with either a dongquai and Astragalus mixture (3mL/day)orenalapril (10 mg/kg). The normal control groupreceived saline, and another group received puro-mycin but no treatme nt." After 12 weeks the un-treated rats showed marked renal fibrosis. How-ever, dong quai and Astragalus significantlyre-tarded the progression of renal fibrosis and dete-rioration of renal histological dam age, with effectscomparable to enalapril.' '

Antispasmodic ActivityLigustil ide, butylidenephthaiide.andbutylphthalide were found to have antispasmodic

activity against rat uterine contractions and in othersmooth muscle systems. The components werecharacterized as non-specific antispasmodics witha mechanism different from papaverine.^'- linical IndicationsCardiovascular Disease

Dong quai has demonstrated quinidine-like activity on the heart.-Itcan prolong the re-fractory period, low er blood pressure, and correctexperimental atrial fibrillation induced by atro-pine.pituitrin. strophanthin. acetylcholine. or elec-trical stim ulation.'" Dong quai can dilate the coro-nary vessels, increase ctironary flow, and reducerespiratory rate. An animal study usingawater-based extract of dong quai demonstrated a markedprotective effect against myocardial dysfunctionand myocardial injury induced by ischemia.*

A recent histological study demonstrateda preparation ofdong quai and Ligusticum sig-nificantly protected human umbilical vein endo-thelial cells against hydrogen peroxide damage,primarilybyinhibiting reactive oxygen speciesformation and promoting endothelial nitric oxidesynthase (eNOS) expression.'' This might be themechanism ofthe above-noted cardio-protectiveaetivity.Nephrotic Syndrome

An herbal preparation of Astragalus anddong quai has long been used inChinatotreatnephrotic syndrome,as it was thought toelicitantifibrotic effects. In arecent anim al study theAstragalus/dong quai mixture was found to retardthe progression of renal fibrosis and deteriorationof renal function with an effect similar to the drugenaiapril."Dysmenorrhea

Two general components of dong quaiaffect uterine smooth muscle inopposite ways.The antispasmodic componentof the herbisat-tributed to constituents ofthe volatile oil. such as

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l ig u s t i l id e . b u ty i id e n c p h th a l id e . andbutylphth alide. As a balance, the uterine stim ulat-ing aspect is attributedtothe water-soluble, non-volatile constituentsofthe he rb.' -^'"Animal experimentsin vivo have demon-strated increased excitability ofthe uterus., wherethe contractive rhythm ol' uterine smooth musclechanged from fast. weak, and irregular to slower,stronger, and more coordinated (more rhythmic),depending on uterine tone. This i.s believedto bethe pharmacological basis for use of dong quaiduring dysmenorrhea.' The root does notexertestrogenic activity.""^

MenopauseOne ofthe most common applications fordong quaiinthe U nited Statesis forreliefofva-somotor symptoms associated with menopau.se.Such symptoms include hoiflashes, skin flush-ing, perspiration,andchills.The meehanismofaction, however,is still unclear. Inarandomized,double-blind, placebo-controlled clinical trial. 71postmenopausal women received either dong quairoot (4.5 g) or placebo daily for 24 weeks.'"'Therewere no differences invasomotor symptomsbe-tweenthetwo groups,andthere appearedto beno estrogen-like effectson vaginal epithelial ti.s-sue. The useofdong quai alone can be criticizedbecause traditional Chinese practitioners neverprescribeitalone, but rather in combination withseveral otherherbs.The researchers chose to studydong quai alone because many women in theUnited States who takeit to relieve menopausalsymptoms purchase the herb over-the-counterasa single entity. Women should be discouraged fromusing dong quai alone for the relief of menopausalcomplaints.An herbal mixture containing Attgeiica.sitietisisroot.Paeonia iactiflorctroot. Liguslicumrhizome. Atraetylodes rhizome. Alismatisrhi-zome, andScleroTiumpoiia has been reportedtoreduce menopausal disturbances, including vaso-motor symptoms by 70 percent."* '^

Drug-Botanical InteractionsDong quai may potentiate the therapeuticand adverse effeets associated with antiplatelet

medication. A small pharmacokinetic study con-ducted on rabbits observed the interaction betweendong quai and warfarin. Single subcu taneous do.sesof warfarin(2 mg/kg) were administered withorwithout oral dong quai extract (2 g/kg. twice dailyfor three days). The dong quai treatmentdid noteffeet prothrombin timeon itsown.but signifi-cantly loweredthevalue three days after co-ad-ministration with warfarin. No significant varia-tion in the phariiiacokineiic p arameters of warfarinwere observed after dong quai treatmentfor ei-ther single-dose administration or steady-stateconcentrationsof warfarin.-'^

Ina ca.se report,a46-year-old woman,w hohad been taking5mg/day warfarin for nearlytwo years and had an international normalized ra-tio (INR) stabilized at2-3.experienced an increa.sein her INR to 4.9 over the course of approximatelytwo months."' Changes in medication regimen,diet, alcohol consumption,orother lifestylefac-tors thatmayaffect INR we re sufficiently ruledout. However,the patient stated thatfor the pastfour weeks she hadbeen taking dong quaiforperimenopausal symptoms as recommended by anherbalist,and hadforgotten to mention thisear-lier. The dosage was one 565-mg tablet 1-2 tim es/day. The patient was instmcted to discontinue dongquai. and within four weeksher INR declinedtothe therapeutic rangeof2.48.Inviewofthisin-formation, cautionisadvisedfor patients receiv-ing chronic treatment with warfarin.Side Effects and Toxicity

Although noreported .side effects haveoccurred with the use of authentic dong quai. vari-ous sources continuetowarnofpotential p hoto-sensitivity reactions due to psoralen and bergaptencontent.^ Both psoralen and bergapten arefuranocoumarins widely studiedfortheir p hoto-sensitizing properties.'^ Other related .speciesofAngelica (e.g..A. gigas. A. dahurica andA.piihescen.s)pose a greater risk than d ong quai du eto their higher furanoeoumarin content.'

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The re ha.s been one isolated case of a manwho developed gynecom astia (mamm ary glandu-lar hyperplasia) after taking dong quai capsulesdailyforapproximately one m onth.' The labelonthe bottle indicated "l()09f dong quai {Aiii>elicasinensis) root powderONo fillersoradditives."Th epat ient discontinued the "dong qua i" pills andhis gynecom astiahadregressed com pletely whenexamined three months later.Itis important to notethatthepillsin question werenotproperlyana-lyzedtoctinfirmorrefute the purityof the prod-uct. Consequently,theauthors couldnotruleoutpresenceofa pharmacologically active contami-nant that mayhave contributed to thepatient'scondition.'''The oral LD^,^of aconcentrated (8:1to16:1) dong quai extract inratswasmeasuredat100g/kgbody w eight.- Intravenous administra-tionoftheessentialoil toanimalsatdosesof 1mL/kgcancausea drop in blood pressureanddepressionofrespiration.^Contraindications

Dong quai isco ntraindicated in preg-nancy, particularly in the first trimester,due topotentia l uter ine s timulant and relaxant ef-fects.--'^-"Dosage

Dong quai isavailable inseveral differ-ent forms,anddosages vary accordingly. Typicaloral dosages-' '^ are asfollows:Dried root:3-15gdailybydecoctionPowdered root: 1-2g3times dailyTea:I cup1-3times daily(I gpercup)Tincture (1:2):4-Sm L( l- 2 tsp)perdayCapsules/Tablets: 500 mg1-6times daily

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11. WangH. Li J,YuL. et al.Antifibrotic effectofthe Chinese herbs.Astragalus mongholicusandAngelica sinensis. in a ratmodelofchrt>nic pun)mycin aminonuclcosidc ncphro-sis.LifeSci2004:74:1645-1658.

12. KoWC.Anewly i.solated antispasmodic -butylidenephthalidc.Jpn JPhannacol1980:30:85-91.

13. HouYZ. ZhaoGR.YangJ. et al.Protectiveeffect ofLigiisticum chuanxiongandAngelicasinensisonendothelial cell damage inducedbyhydrogen peroxide.LifeSci2004:75:1775-1786.^

14. HirataJD. Swiers/LM. ZellB. et al.Doesdong quai have estrogenic effects inpostmeno-pausal women? A double-blind, placebo-controlled trial.Eertil Sterit 1997:68:981-986.

15. Heck AM. DeWitt BA.Lukes AL. Potentialinteractions between alternative therapiesandwarfarin.Am JHealth Svsi Phann2000:57:1221-1227.

16. PageRL 2nd.Lawrence JD. Potentiationofwarfarinbydong quai.Pharmacotherapy1999;19:870-876.

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ngelica sinensi17. Jcllin JM. GregoryP.Bat/. F.clal.Pharm acist s L etter/Prescriher sLetterNatural Medicines Comprehensive Database.3"'ed. S luckion. CA : ThcrapciiiiL' R esearchFaculty: 2(){)():3S()-3HI.18. OohSY.LdhKC. Gynaecoma.stiaandtheherbal ionic "Don>2 Quai". Singapore Med J2()()l;42:i 15-116.

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Kiong HN. Article: gynaecom astiaand theherbal tonic "Dotiij Quai"*. Singapore Med J2001:42:286-287.^Brinker F.Herb C oniralndicatlons and Drughueraclions. Sandy. OR: Eclectic MedicalPublication.s: 1998:117.

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