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Dong Quai

Scientific Name(s): Angelica sinensis (Oliv.) Diels.
Common Name(s): Chinese angelica, Danggui, Dong quai, Tang-kuei

Clinical Overview

See also: Orencia

Use

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

See Drug Interactions section.

Adverse Reactions

Case reports exist of fever, gynecomastia, 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.Tang 1992, Mizukami 1995

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.Medline 2009 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.Haines 2008

Chemistry

The chemistry of A. sinensis is distinct from that of other species in the genus. While coumarins have been reported from this speciesHata 1967 a recent comparative study of commercial dong quai products and related speciesZschocke 1998 found coumarins to be lacking, while the lactone Z-ligustilide was a major constituent.Chen 1984 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.Sheu 1987, Hon 1990, Chen 1984 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.Ji 1999

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.Okuyama 1990 Ferulic acid was also detected in this species.Kwon 1997

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.Kozawa 1980, Baba 1982

The common polyacetylene falcarindiol has been isolated from various species of Angelica.Zschocke 1998 Polysaccharides have been isolated from different species of Angelica; however, they have not been characterized sufficiently to permit comparison.Choy 1994 Simple plant sterols and lipids have also been found.Tani 1984 Reviews of the phytochemistry of Radix A. sinensis have been published.Chen 2013, Wei 2016

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. Results from studies evaluating dong quai’s estrogenic effects have been conflicting, possibly due to differences in the preparations studied, and there is some data to suggest serotonergic activity.Hajirahimkhan 2013

A. sinensis is most commonly administered as a multi-ingredient preparation (often combined with Astragalus membranaceus), making both attribution of effect and comparison of traditional Chinese medicine applications with Western medicine difficult.Hook 2014, Lin 2017

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.Lam 2008, Zhao 2008, Yang 2002 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.Sung 1982 The simple lactone ligustilide is thought to be a major bioactive principle of dong quai. Its antiasthmatic action was studied in guinea pigs.Tao 1984

Anti-inflammatory effects

Chemical constituents from related species have demonstrated anti-inflammatory effects in vitro and in animal experiments.Kosuge 1985, Ko 1992, Guh 1996, Chen 1995, Liu 1998, Magdalou 2015 Histamine antagonism and analgesic properties have also been demonstrated.Chen 1995, Kimura 1997

Antioxidant

An in vitro study demonstrated a protective effect of A. sinensis on hydrogen peroxide-induced endothelial cell damage.Hou 2004

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.Ko 1980

Cancer

In vitro experiments evaluating A. sinensis extracts found induced apoptosism activity against cervical and hepatocellular carcinoma and leukemia cell linesChen 2007, Chae 2004 and inhibitory actions against a number of tumors.Lee 2006, Tsai 2005

A large, prospective observational study in postmenopausal women during a 7-year period found that dong qui use was not associated with an increased risk of breast cancer (hazards ratio 1.27 [95% confidence interval, 0.76 to 2.13]), but the number of patients reporting use was less than 500 out of a study population of more than 30,000 patients.Brasky 2010

CNS

The furocoumarin phellopterin has been characterized as a competitive partial agonist of central benzodiazepine receptors by gamma-aminobutyic acid (GABA) and TBPS shift assaysDekermendjian 1996 and to bind with high affinity to benzodiazepine receptors in vitro; however, other closely related furocoumarins were weaker or inactive.Bergendorff 1997 The ligustilide and butylidenephthalide constituents of Japanese angelica root may exert central noradrenergic or GABA activity.Matsumoto 1998

Female reproductive system disorders

Animal data

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. 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-stimulant effect is due to the water-soluble components.Ko 1980

Clinical data

Premenstrual syndrome/Dysmenorrhea

Limited clinical trials have been conducted in settings other than China, and those for which efficacy is suggested often utilise multi-ingredient preparations. Ethnic differences in hormonal levels and menopausal symptoms may account for variation in attribution of effect. Reviews suggest evidence for effect in dysmenorrhea exists; however studies included were of short duration and low quality.Hook 2014

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.Haines 2008, Hirata 1997, Menopause 2004, Cheema 2007 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.Hirata 1997, Hook 2014 In addition, Chinese traditional medicine does not recommend the use of dong quai alone, but rather in combination with other plant extracts.Menopause 2004 The North American Menopause Society concludes that dong quai is no more effective than placebo and that data on estrogenic activity are inconclusive.Menopause 2004 The Society of Obstetricians and Gynaecologists of Canada revised clinical practice guidelines (2014) on managing menopause do not recommend dong quai for reducing menopausal symptoms based on a lack of evidence to support clinical benefit.Reid 2014 The Endocrine Society clinical practice guidelines for the treatment of symptoms of the menopause (2015) recommend counseling patients on the lack of consistent evidence for benefit of complementary medicine therapies, including dong quai, as an alternative nonhormonal therapy for vasomotor symptoms (weak recommendation; low quality evidence).Stuenkel 2015

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.Kronenberg 2002, Haimov-Kochman 2008, Haimov-Kochman 2005, Lau 2005

A small pilot study conducted on the effects of dong quai on hot flashes in prostate cancer patients receiving lutenizing hormone-releasing hormone therapy found no significant benefit compared with placebo for the frequency, severity, or duration of hot flashes. There was also no difference between dong quai and placebo groups for prostate-specific antigen levels and digital rectal examination results during the 3-month study.Al-Bareeq 2010

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.Burke 2002 Dong quai has not been investigated alone for its effect in this indication.

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.Wang 2004

Dosing

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.Burke 2002, Hirata 1997, Haimov-Kochman 2005, Lau 2005

The content of A. sinensis in some commercially available preparations has been questioned.Hook 2014

Pregnancy / Lactation

Avoid use.Brinker 1998 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.Ko 1980

Interactions

Studies indicate A. sinensis extracts increase liver CYP2D6 and CYP3A4 activity, with potential for herb-drug interactions.Hook 2014

Agents with Antiplatelet Properties: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification.Stanger 2012, Ulbricht 2008, Tsai 2013

Anticoagulants: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification.Stanger 2012, Ulbricht 2008, Tsai 2013

Herbs (Anticoagulant/Antiplatelet Properties): May enhance the adverse/toxic effect of other Herbs (Anticoagulant/Antiplatelet Properties). Bleeding may occur. Consider therapy modification.Stanger 2012, Ulbricht 2008, Tsai 2013

Nonsteroidal Anti-Inflammatory Agents: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Consider therapy modification.Stanger 2012, Ulbricht 2008, Tsai 2013

Salicylates: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Consider therapy modification.Tsai 2013, Ulbricht 2008

Thrombolytic Agents: Herbs (Anticoagulant/Antiplatelet Properties) may enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Consider therapy modification.Stanger 2012, Ulbricht 2008, Tsai 2013

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, the risk appears to be limited.Kronenberg 2002, Haimov-Kochman 2005, Hann 1991, Leung 1996

Fever was reported in a clinical trial.Page 1999

Hypertension has been reported with the use of this herb.Jalili 2013

A case of gynaecomastia was reported, but causality is unclear.Goh 2001 The possibility of dong quai tablet contamination has been raised.Fugh-Berman 2003, Kiong 2001

In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, dong quai has been recognized as a product with anticoagulant effects which may increase bleeding risk when used with anticoagulants. The guidance noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].Page 2016

Toxicology

To date, phytoestrogen-containing herbs have not been associated with the negative health effects seen with synthetic estrogen. However, use with caution in individuals on hormone replacement therapy, oral contraceptives, or those with a history of estrogen-dependent tumors, endometrial cancer, thromboembolic disease, or stroke.Piersen 2003, Menopause 2004

The oral median lethal dose (LD50) 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.Yang 2002

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