Scientific Name(s): Angelica sinensis (Oliv.) Diels. Family: Apiaceae (carrot) Synonym: Umbelliferae family
Common Name(s): Dong quai , danggui , tang-kuei , Chinese angelica
Dong quai is used in combination with other plant extracts in Chinese traditional medicine as an analgesic for rheumatism, an allergy suppressant, and in the treatment of menstrual disorders. Dong quai and its chemical constituents possess antiasthmatic, antispasmodic, anti-inflammatory, and anticoagulant properties. Clinical trials supporting traditional uses are limited. It has also been used to flavor liqueurs and confections.
Several forms of the plant exist and dosages vary widely: crude root extract by decoction ranges from 3 to 15 g/day; while in combination, preparations 75 mg to 500 mg may be taken up to 6 times a day.
Relative contraindications in patients receiving warfarin, heparin, or other anticoagulant/antiplatelet therapy, in those with breast cancer, or in the first trimester of pregnancy.
Avoid use. Uterine stimulant and relaxant activity have been reported with A. sinensis , while a related species, Angelica archangelica L., was a reported abortifacient and affected the menstrual cycle.
Warfarin, heparin, and other antiplatelet therapy due to anticoagulant/antiplatelet action of A. sinensis .
Case reports exist of fever, gynaecomastia, and bleeding with concurrent warfarin use. A risk of photosensitization exists.
Data are limited. Chemical constituents have demonstrated cytotoxic properties.
A. sinensis (Oliv.) Diels is synonymous with A. polymorpha var. sinensis (Oliv.). Three species of angelica are monographed separately in the Pharmacopoeia of the People's Republic of China : dong quai, the root of A. sinensis ; bai zi, the root of Angelica dahurica (Fisch.) Benth. et. Hook. f. or A. dahurica var. formosana (Boiss.) Shan et Yuan; and du huo, the root of A. pubescens Maxim. f. biserrata Shan et Yuan. In Korea, A. gigas Nakai is used medicinally, while in Japan, A. acutiloba Kitagawa is used. The European A. archangelic L. is used to flavor liqueurs and confections. While botanically related, the various species of Angelica , which differ in chemistry, pharmacology, and toxicology should not be confused. A molecular biology study of A. acutiloba may lead to efficient methods for distinguishing raw materials. 1 , 2 , 3
Dong quai has been used for thousands of years in traditional Chinese, Korean, and Japanese medicine and continues to be popular in China and elsewhere. It is used primarily for health issues in women and has been termed “female ginseng.” It reported to be a blood strengthener and has been used for cardiovascular conditions, inflammation, headache, infections, and nerve pain. 4 It is also used to treat a wide range of conditions including menstrual disorders and other gynecological issues, as an analgesic in rheumatism, and in suppressing allergy symptoms. It is promoted for similar uses in the American herb market. 5
The chemistry of A. sinensis is distinct from that of other species in the genus. While coumarins have been reported from this species, 6 a recent comparative study of commercial dong quai products and related species 7 found coumarins to be lacking, while the lactone Z -ligustilide was a major constituent. 8 In this study, A. sinensis more closely resembled Levisticum officinale in chemical composition than other species of Angelica . Thus, there is justification for terming the latter plant European dong quai. Several other lactones related to ligustilide have been found in A. sinensis . 9 , 10 , 11 Ferulic acid and its esters were also found in A. sinensis . A capillary electrophoresis method for measuring ferulic acid in A. sinensis has been published. 12
In contrast, the roots of A. dahurica were found to contain an abundance of coumarins. Imperatorin and isoimperatorin are the major constituents, with many other related compounds (eg, bergapten, phellopterin, scopoletin) reported. 13 Ferulic acid was also detected in this species. 14
The root of A. pubescens contains coumarins, but with some differences from A. dahurica . The simple prenylcoumarin, osthole, and the linear furocoumarins, columbianadin and columbianetin acetate, are the major constituents, while the coumarins, angelols A-H, are characteristic of the species. 15 , 16
The common polyacetylene falcarindiol has been isolated from various species of Angelica . 7 Polysaccharides have been isolated from different species of Angelica ; however, they have not been characterized sufficiently to permit comparison. 17 Simple plant sterols and lipids have also been found. 18
Uses and Pharmacology
Dong quai is widely used in the United States to treat hot flashes and other symptoms of menopause, despite a lack of clinical data.Dysmenorrhea
In vivo animal studies suggest that the basis for dong quai use in dysmenorrhea lies in its action of increasing excitability of the uterus; the rhythm of contraction changed from fast, weak, and irregular to slow, strong, and more regular. 19 It has been postulated that the antispasmodic effects of dong quai are related to the volatile oil constituents ligustilide, butylidenephthalide, and butylphthalide, while the uterine-stimulating effect is due to the water-soluble components. 19 Clinical trials are lacking.Menstrual migraine
Among women with either menstrual migraine or simple migraine without aura, a combination preparation of soy isoflavones, black cohosh, and dong quai taken daily for 24 weeks decreased the frequency and severity of attacks. 20 Dong quai has not been investigated alone for its effect in this indication.Menopausal vasomotor symptoms
Randomized, double-blind, placebo-controlled trials of A. sinensis as a single agent and in combination found no difference for dong quai over placebo for menopausal vasomotor symptoms. 5 , 21 , 22 , 23 No effect on endometrial thickness or on the level of estradiol or estrone was found in a trial of dong quai alone. The study material was standardized for ferulic acid content. 21 In addition, Chinese traditional medicine does not recommend the use of dong quai alone, but rather in combination with other plant extracts. 22 The North American Menopause Society concludes that dong quai is no more effective than placebo and that data on estrogenic activity are inconclusive. 22
Despite evidence that dong quai does not bind to estrogen receptors, experiments have demonstrated the ability of A. sinensis extracts to stimulate breast cancer cells lines (MCF-7 and BT-20). Considering the lack of evidence for effect on menopausal vasomotor symptoms, dong quai should not be used by menopausal women with breast cancer. 24 , 25 , 26 , 27Other effects
In vitro and in vivo animal experiments suggest that A. sinensis possesses angiogenic activity. Experiments on human periodontal and bone tissue have been conducted. 28 , 29 , 30 The clinical relevance of these findings has yet to be confirmed.Antiallergy
An aqueous extract of A. sinensis inhibited IgE-antibody production in a mouse model of atopic allergy. The extract was active orally and the activity was retained on dialysis, indicating that it was caused by high molecular weight components of the extract. 31 The simple lactone ligustilide is thought to be a major bioactive principle of dong quai. Its antiasthmatic action was studied in guinea pigs. 32Anti-inflammatory effects
Chemical constituents from related species have demonstrated anti-inflammatory effects in vitro and in animal experiments. 33 , 34 , 35 , 36 , 37 Histamine antagonism and analgesic properties have also been demonstrated. 36 , 38Antioxidant
An in vitro study demonstrated a protective effect of A. sinensis on hydrogen peroxide-induced endothelial cell damage. 39Antispasmodic
Ligustilide and the related butylidenephthalide and butylphthalide were found to have antispasmodic activity against rat uterine contractions and other smooth muscle systems. The compounds were characterized as nonspecific antispasmodics with a mechanism different from that of papaverine. 19Cancer
In in vitro experiments, A. sinensis extracts have induced apoptosism activity against cervical and hepatocellular carcinoma and leukemia cell lines, 8 , 40 and inhibitory actions against a number of tumors. 41 , 42CNS
The furocoumarin phellopterin has been characterized as a competitive partial agonist of central benzodiazepine receptors by gamma-aminobutyic acid (GABA) and TBPS shift assays, 43 and to bind with high affinity to benzodiazepine receptors in vitro; however, other closely related furocoumarins were weaker or inactive. 44 The ligustilide and butylidenephthalide constituents of Japanese angelica root may exert central noradrenergic or GABA activity. 45Renal
Nephrotic syndrome has been traditionally treated with A. senensis and Astragalus mongholicus by Chinese practitioners. Animal models demonstrated an efficacy with these plant extracts similar to that of enalapril in preventing renal fibrosis and limiting the deterioration of renal function. 46
Several forms of the plant exist and dosages vary widely: crude root extract by decoction ranges from 3 to 15 g/day; powdered root, 1 to 2 g 3 times a day; and tablets 500 mg up to 6 times a day.
In a clinical trial investigating use in menopause, dong quai 4.5 g was administered daily for 24 weeks. In combination, dong quai 100 mg standardized to 1% ligustilide was similarly used daily. 20 , 21 , 26 , 27
Avoid use. 48 A. sinensis , reported uterine stimulant and relaxant activity have been reported with, while a related species, Angelica archangelica L., was a reported abortifacient and affected the menstrual cycle. 19
The coumarins of Angelica species have been associated with their bioactivity and toxicity; however, the low coumarin content of A. sinensis minimizes the significance in dong quai pharmacology. In other species of Angelica , coumarins clearly play an important role. 49
Case reports of warfarin potentiation exist 47 ; however, the mechanism for this interaction is unclear. Studies in rabbits demonstrated effects on clotting time. 47 Inhibition of platelet aggregation has been demonstrated in animal experiments, 47 , 50 while sodium ferulate exerted antiplatelet action in a trial of patients with ulcerative colitis. 51
The Angelica species has demonstrated photosensitization, and a theoretical interaction exists with other photosensitizers, such as St. John's wort or sulfa and quinolone antimicrobials. 52
Furanocoumarins, such as bergapten and psoralen, have been widely studied for their photoactivated toxicity; however, only A. gigas (Korean angelica) has caused photodermatitis. The risk of phototoxicity should be correlated with the content of specific toxic furocoumarins; in the case of A. sinensis , there appears to be little risk. 24 , 26 , 53
Fever was reported in a clinical trial. 47
The oral LD 50 of concentrated dong quai extract has been estimated at 100 mg/kg. Intravenous administration of 1 mL/kg of the essential oil in rabbits resulted in hypotension and respiratory suppression. Phenol and certain furocoumarin groups found in dong quai have demonstrated cytotoxic properties. 30
Bibliography1. USDA, ARS, National Genetic Resources Program. Germplasm Resources Information Network - (GRIN) [Online Database]. National Germplasm Resources Laboratory, Beltsville, Maryland. http://www.ars-grin.gov/cgi-bin/npgs/html/taxon.pl?406655 . 11 March 2009. (Accessed October 2008)
2. Tang W, Eisenbrand G. Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine . Berlin: Springer-Verlag; 1992:113-125.
3. Mizukami H. Amplification and sequence of a 5s-rRNA gene spacer region from the crude drug “angelica root”. Biol Pharm Bull . 1995;18(9):1299-1301.
4. Dong quai ( angelica sinesis [oliv.] Dies), Chinese angelica. http://www.nlm.nih.gov/medlineplus/druginfo/natural/936.html . Accessed February 26, 2009.
5. Haines CJ, Lam PM, Chung TK, Cheng KF, Leung PC. A randomized, double-blind, placebo-controlled study of the effect of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women. Climacteric . 2008;11(3):244-251.
6. Hata K, Kozawa M, Ikeshiro Y. [On the coumarins of the roots of Angelica polymorpha Maxim. [in Japanese] Yakugaku Zasshi . 1967;87(4):464-465.
7. Zschocke S, Liu J-H, Stuppner H, Bauer R. Comparative study of roots of Angelica sinensis and related Umbelliferous drugs by thin layer chromatography, high-performance liquid chromatography, and liquid chromatography-mass spectrometry. Phytochem Anal . 1998;9(6):283-290.
8. Chen QC, Lee J, Jin W, et al. Cytotoxic constituents from Angelicae sinensis radix. Arch Pharma Res . 2007;30(5):565-569.
9. Sheu Sj, Ho VS, CHen YP, Hsu HY. Analysis and processing of Chinese herbal drugs; VI. The study of Angelicae radix . Planta Med . 1987;53(4):377-378.
10. Hon P-M, Lee C-M, Choang TF, Chui K-Y, Wong HN. A ligustilide dimer from Angelica sinensis . Phytochemistry . 1990;29(4):1189-1191.
11. Chen Y, et al. Analysis of the composition of Angelica sinensis – determination of the essential oil composition by capillary column GC/MS. Gaodeng Xuexiao Huaxue Xuebao . 1984;5:125.
12. Ji SG, Chai YF, Wu YT, et al. Determination of ferulic acid in Angelica sinensis and Chuanxiong by capillary zone electrophoresis. Biomed Chromatogr . 1999;13(5):333-334.
13. Okuyama T, Takata M, Nishino H, Nishino A, Takayasu J, Iwashima A. Studies on the antitumor-promoting activity of naturally occurring substances. II. Inhibition of tumor-promoter-enhanced phospholipid metabolism by umbelliferous materials. Chem Pharm Bull . 1990;38(4):1084-1086.
14. Kwon YS, Kobayashi A, Kajiyama S, Kawazu K, Kanzaki H, Kim CM. Antimicrobial constituents of Angelica dahurica roots. Phytochemistry . 1997;44(5)887-889.
15. Kozawa M, Baba K, Matsuyama Y, Hata K. Studies on coumarins from the root of Angelica pubescens Maxim. III. Structures of various coumarins including angelin, a new prenylcoumarin. Chem Pharm Bull . 1980;28(6):1782-1787.
16. Baba K, Matsuyama Y, Kozama M. Studies on coumarins from the root of Angelica pubescens Maxim. IV. Structures of angelol-type prenylcoumarins. Chem Pharm Bull . 1982;30(6):2025-2035.
17. Choy Y, Leung KN, Cho CS, Wong CK, Pang PK. Immunopharmacological studies of low molecular weight polysaccharide from Angelica sinensis . Am J Chin Med . 1994;22(2):137-145.
18. Tani S, Fujiwara H, Kato A. Studies on constituents of Angelica dahurica . II. Identification of gamma-nonalactone and gamma-decalactone by GC and GC/MS as a part of the odor components. J Nat Prod . 1984;47(4):734.
19. Ko WC. A newly isolated antispasmodic - butylidenephthalide. Jpn J Pharmacol . 1980;30(1):85-91.
20. Burke BE, Olson RD, Cusack BJ. Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine. Biomed Pharmacother . 2002;56(6):283-288.
21. Hirata JD, Swierz LM, Zell B, Small R, Ettinger B. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril . 1997;68(6)981-986.
22. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause . 2004;11(1):11-33.
23. Cheema D, Coomarasamy A, El-Toukhy T. Non-hormonal therapy of post-menopausal vasomotor symptoms: a structured evidence-based review. Arch Gynecol Obstet . 2007;276(5):463-469.
24. Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med . 2002;137(10):805-813.
25. Haimov-Kochman R, Brzezinski A, Hochner-Celnikier D. Herbal remedies for menopausal symptoms: are we cautious enough? Eur J Contracept Reprod Health Care . 2008;13(2):133-137.
26. Haimov-Kochman R, Hochner-Celnikier D. Hot flashes revisited: pharmacological and herbal options for hot flashes management. What does the evidence tell us? Acta Obstet Gynecol Scand . 2005;84(10):972-979.
27. Lau CB, Ho TC, Chan TW, Kim SC. Use of dong quai ( Angelica sinensis ) to treat peri- or postmenopausal symptoms in women with breast cancer: is it appropriate? Menopause . 2005;12(6):734-740.
28. Lam HW, Lin HC, Lao SC, et al. The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo. J Cell Biochem . 2008;103(1):195-211.
29. Zhao H, Alexeev A, Sharma V, Guzman LD, Bojanowski K. Effect of SBD.4A – a defined multicomponent preparation of Angelica sinensis – in periodontal regeneration models. Phytother Res . 2008;22(7):923-928.
30. Yang Q, Populo SM, Zhang J, Yang G, Kodama H. Effect of Angelica sinensis on the proliferation of human bone cells. Clin Chim Acta . 2002;324(1-2):89-97.
31. Sung C, Baker AP, Holden DA, Smith WJ, Chakrin LW. Effect of extracts of Angelica polymorpha on reaginic antibody production. J Nat Prod . 1982;45(4):398-406.
32. Tao JY, Ruan YP, Mei QB, et al. [Studies on the antiasthmatic action of ligustilide of dang-gui, Angelica sinensis (Oliv.) Diels. [in Chinese] 1984;19(8):561-565.
33. Kosuge T, Yokota M, Sugiyama K, et al. Studies on bioactive substances in crude drugs used for arthritic diseases in traditional Chinese medicine. II. Isolation and identification of an anti-inflammatory and analgesic principle from the root of Angelica pubescens Maxim. Chem Pharm Bull . 1985;33(12):5351-5354.
34. Ko FN, Wu TS, Lion MJ, Huang TF, Teng CM. Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens . Eur J Pharmacol . 1992;219(1):29-34.
35. Guh J, Yu SM, Ko FN, Wu TS, Teng CM. Antiproliferative effect in rat vascular smooth muscle cells by osthole, isolated from Angelica pubescens . Eur J Pharmacol . 1996;298(2):191-197.
36. Chen Y, Tsai HY, Wu TS. Anti-inflammatory and analgesic activities from roots of Angelica pubescens . Planta Med . 1995;61(1):2-8.
37. Liu J, Zschocke S, Reininger E, Bauer R. Inhibitory effects of Angelica pubescens f. biserrata on 5-lipoxygenase and cyclooxygenase. Planta Med . 1998;64(6):525-529.
38. Kimura Y, Okuda Hl. Histamine-release effectors from Angelica dahurica var. dahurica root. J Nat Prod . 1997;60(3):249-251.
39. Hou YZ, Zhao GR, Yang J, Yuan YJ, Zhu GG, Hiltunen R. Protective effect of Ligusticum chuanxiong and Angelica sinensis on endothelial cell damage induced by hydrogen peroxide. Life Sci . 2004;75(14):1775-1786.
40. Chae HJ, Park KM, Lee GY, et al. Je-chun-jun induced apoptosis of human cervical carcinoma HeLa cells. Acta Pharmacol Sin . 2004;25(10):1372-1379.
41. Lee WH, Jin TS, Tsai WC, et al. Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology . 2006;73(3):141-148.
42. Tsai NM, Lin SZ, Lee CC, et al. The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Clin Cancer Res . 2005;11(9):3475-3484.
43. Dekermendjian K, Ai J, Nielsen M, et al. Characterisation of the furanocoumarin phellopterin as a rat brain benzodiazepine receptor partial agonist in vitro. Neurosci Lett . 1996;219:151-154
44. Bergendorff O, Dekermendjian K, Nielsen M, et al. Furanocoumarins with affinity to brain benzodiazepine receptors in vitro. Phytochemistry . 1997;44(6):1121-1124.
45. Matsumoto K, Kohno S, Ojima K, et al. Effects of methylenechloride-soluble fraction of Japanese angelica root extract, ligustilide and butylidenephthalide, on pentobarbital sleep in group-housed and socially isolated mice. Life Sci . 1998;62(23):2073-2082.
46. Wang H, Li J, Yu L, Zhao Y, Ding W. Antifibrotic effect of the Chinese herbs, Astragalus mongholicus and Angelica sinensis , in a rat model of chronic puromycin aminonucleoside nephrosis. Life Sci . 2004;74(13):1645-1658.
47. Page RL II, Lawerence JD. Potentiation of warfarin by dong quai. Pharmacotherapy . 1999;19(7):870-876.
48. Brinker FJ. Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
49. Hoult JR, Payá Ml. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol . 1996;27(4):713-722.
50. Liu J, Xu SX, Yao XS, Kobayashi H. Angelol-type coumarins from Angelica pubescens f. biserrata and their inhibitory effect on platelet aggregation. Phytochemistry . 1989;39(5):1099-1101.
51. Dong WG, Liu SP, Zhu HH, et al. Abnormal function of platelets and role of angelica sinensis in patients with ulcerative colitis. World J Gastroenterol . 2004;10(4):606-609.
52. Scott GN, Elmer GW. Update on natural product–drug interactions. Am J Health Syst Pharm . 2002;59(4):339-347.
53. Hann S, Park YK, Im S, Byun SW. Angelica-induced phytophotodermatitis. Photodermatol Photoimmunol Photomed . 1991;8(2):84-85.
54. Goh SY, Loh KC. Gynaecomastia and the herbal tonic “Dong Quai”. Singapore Med J . 2001;42(3):115-116.
55. Fugh-Berman A. “Bust enhancing” herbal products. Obstet Gynecol . 2003;101(6):1345-1349.
56. Kiong HN. Article: gynaecomastia and the herbal tonic “Dong Quai”. Singapore Med J . 2001;42(6):286-287.
Copyright © 2009 Wolters Kluwer Health