Dong Quai

Scientific Name(s): Angelica sinensis (Oliv.) Diels. Family: Apiaceae (carrot) Synonym: Umbelliferae family

Common Name(s): Dong quai , danggui , tang-kuei , Chinese angelica

Uses

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.

Dosing

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.

Contraindications

Relative contraindications in patients receiving warfarin, heparin, or other anticoagulant/antiplatelet therapy, in those with breast cancer, or in the first trimester of pregnancy.

Pregnancy/Lactation

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.

Interactions

Warfarin, heparin, and other antiplatelet therapy due to anticoagulant/antiplatelet action of A. sinensis .

Adverse Reactions

Case reports exist of fever, gynaecomastia, and bleeding with concurrent warfarin use. A risk of photosensitization exists.

Toxicology

Data are limited. Chemical constituents have demonstrated cytotoxic properties.

Botany

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

History

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

Chemistry

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 , 27

Other effects
Angiogenesis

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. 32

Anti-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 , 38

Antioxidant

An in vitro study demonstrated a protective effect of A. sinensis on hydrogen peroxide-induced endothelial cell damage. 39

Antispasmodic

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. 19

Cancer

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 , 42

CNS

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. 45

Renal

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

Dosage

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

Pregnancy/Lactation

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

Interactions

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

Adverse Reactions

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

A case of gynaecomastia was reported, but causality is unclear. 54 The possibility of dong quai tablet contamination has been raised. 55 , 56

Toxicology

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

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