Dong Quai

• How It Works

  Dong quai is an herb that has been used in traditional Chinese medicine to nourish blood and treat menstrual and menopausal symptoms.

  Dong quai has been part of traditional Chinese medicine for thousands of years. It is often combined with other herbs in special formulations, and is used to treat menstrual and menopausal symptoms and nourish the blood. Root extracts of dong quai were shown to stop growth of cancer cells in lab studies, but human data are lacking. Results of a few studies that tested whether dong quai could be effective for menopausal symptoms were inconclusive.

  Dong quai has estrogen-like effects and it was shown to increase growth of breast cancer cells in lab experiments. It may also contain compounds that can cause cancer if taken in high doses.

• Purported Uses
  • To relieve symptoms of menopause
    Results from a few studies done in postmenopausal women are inconclusive.
  • To treat dysmenorrhea
    Traditional medicine uses dong quai to treat dysmenorrhea but there is no scientific basis to support this use.
  • To treat premenstrual syndrome
    Although traditionally used to treat premenstrual symptoms, there are no clinical studies to support this claim.
• Do Not Take If
  • You are taking anticoagulants such as warfarin: Dong quai may increase the risk of bleeding, but a human study suggests this effect may be limited.
  • You are pregnant or breastfeeding.
  • You are undergoing radiation therapy: Dong quai can cause photodermatitis, and therefore might worsen the effects of radiation therapy on the skin.
  • You have a hormone-sensitive cancer: Dong quai has estrogenic effects and can further stimulate the growth of cancer cells.
  • You are taking Lisinopril [angiotensin converting enzyme (ACE) inhibitor]: Simultaneous use of dong quai worsened anemia in a study of rats. Whether it has the same effect in humans is not known.
• Side Effects
  • Sensitivity of the skin and eyes to light, causing swelling, itching, and/or redness
  • Excessive development of breasts in men
  • Excessive bleeding due to blood-thinning effect
  • Diarrhea
  • Fever
  • High blood pressure

  Case report

  • Intracranial hemorrhage: In a 53-year-old woman following use of an herbal supplement containing red clover, dong quai, and Siberian ginseng for hot flashes associated with perimenopause. Her symptoms resolved after discontinuing use of the supplement.
• Scientific Name

  Angelica sinensis

• Clinical Summary

  Dong quai is an herb, the root of which has been used in traditional Chinese medicine for thousands of years. It is often combined with other herbs in formulations. Dong quai is also available as a dietary supplement and promoted as a woman’s herb to treat menstrual and menopausal symptoms. In vitro, dong quai extracts have demonstrated antitumor ^{(7) (8) (9) (10)}, pro-apoptotic ^(40) (41), anti-metastatic ⁽⁴¹⁾, anti-tuberculosis (TB) ⁽¹¹⁾, neuroprotective ⁽³²⁾, and hematopoeitic ⁽³⁴⁾ effects. In animal studies, polysaccharides extracted from dong quai root showed protective effects against cyclophosphamide-induced toxicity ⁽¹²⁾, doxorubicin-induced cardiotoxicity ⁽¹³⁾, and radiation-induced pneumonitis ⁽¹⁴⁾. However, these effects have not been evaluated in humans.

  Data from an epidemiologic study suggest that dong quai consumption is associated with reduced risk of subsequent endometrial cancer in breast cancer survivors ⁽³⁹⁾. However, clinical trial data regarding efficacy of dong quai for menopausal symptoms are inconclusive ^{(1) (2) (3) (4) (5) (6) (29) (33)}. A small study done in men with hot flashes did not find dong quai effective ⁽³¹⁾.

  Dong quai exhibits estrogenic activity in vitro ⁽¹⁵⁾ and stimulates proliferation of MCF-7 cells ^(16) (17). Until definitive efficacy and safety data are available, patients with hormone-sensitive cancers should avoid this herb.

• Purported Uses
  • Dysmenorrhea
  • Health maintenance
  • Menopausal symptoms
  • Premenstrual syndrome
  • Spasms
• Mechanism of Action

  Ferulic acid, a constituent of dong quai, may play an important role in treating osteoarthritis by reducing hydrogen peroxide-induced interleukin IL-1beta, tumor necrosis factor TNF-alpha, matrix metalloproteinases MMP-1 and MMP-13, and by increasing SOX9 gene expression. SOX9 is a protein involved in the establishment and maintenance of the phenotype of chondrocytes  ⁽³⁵⁾. Dong quai polysaccharides demonstrated anti-osteoarthritic activity by stimulating insulin-like growth factor 1 (IGF1) and IGF1 receptor gene expression, thereby promoting UDP-sugars and glycosaminoglycan synthesis ⁽³⁷⁾. Another compound promotes wound healing and bone regeneration by inducing osteoblast proliferation and hyaluronic acid deposition ⁽²⁵⁾.

  An aqueous extract from dong quai was reported to have estrogen-agonist activity, and stimulated proliferation of both estrogen receptor-positive and -negative breast cancer cells ⁽¹⁷⁾. It also protected against radiation-induced pneumonitis by downregulating proinflammatory cytokines such as TNF-alpha and TGF-beta1 in a murine model ⁽¹⁴⁾. Subcutaneous injection of dong quai extract protected mice against cyclophosphamide-induced cytotoxicity by promoting recovery from leukopenia ⁽¹²⁾. The antitumor effects of dong quai may be due to its inhibitory effects on invasion and metastasis of carcinoma cells ⁽⁹⁾ and by suppression of tumor growth ^{(7) (8) (10)} that may be mediated by Nur77-dependent apoptosis ^(23) (24). However, dong quai extracts also promote angiogenesis – which plays a key role in both physiologic and disease processes – by inducing proliferation and migration of endothelial cells by upregulating VEGF expression ⁽²⁶⁾.

• Contraindications
  • Pregnant and breastfeeding women should avoid dong quai ⁽²⁷⁾.
  • Patients with hormone-sensitive cancers should avoid dong quai because it has estrogenic effects ⁽¹⁵⁾.
• Adverse Reactions

  Bloating, apetite loss ⁽¹⁸⁾, diarrhea, photosensitivity ⁽¹⁹⁾, gynecomastia ⁽²⁰⁾, and hypertension ⁽⁴³⁾.

  Case Report
  Subarachnoid hemorrhage: In a 53-year-old woman following use of an herbal supplement containing red clover, dong quai, and Siberian ginseng for hot flashes. Her symptoms resolved after discontinuing use of the supplement ⁽³⁰⁾.

• Herb-Drug Interactions

  Anticoagulants: Dong quai may have additive anticoagulant effect ⁽²¹⁾. However, such effect appears to be limited in a human study ⁽⁴⁴⁾.
  Cytochrome P450 substrates: Prolonged use of dong quai can induce CYP3A4 by activating pregnane X receptor ⁽³⁶⁾. This may reduce the blood levels and effectiveness of substrate drugs.
  Lisinopril [angiotensin converting enzyme (ACE) inhibitor]: Concurrent use with dong quai exacerbated anemia in a murine model ⁽⁴²⁾. Clinical relevance has yet to be determined.

• Herb Lab Interactions

  Elevated PT / INR  ⁽²¹⁾

• References

  1. Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am Fam Physician. 2006;73(3):457-464.

  2. 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.

  3. Fugate SE, Church CO. Nonestrogen treatment modalities for vasomotor symptoms associated with menopause. Ann Pharmacother. 2004;38(9):1482-1499.

  4. Kupfersztain C, Rotem C, Fagot R, Kaplan B. The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report. Clin Exp Obstet Gynecol. 2003;30(4):203-206.

  5. Rotem C, Kaplan B. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecol Endocrinol. 2007;23(2):117-122.

  6. TNAM Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause. 2004;11(1):11-33.

  7. Lee WH, Jin JS, Tsai WC, et al. Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology. 2006;73(3):141-148.

  8. Ng SS, Figg WD. Antitumor activity of herbal supplements in human prostate cancer xenografts implanted in immunodeficient mice. Anticancer Res. 2003;23(5A):3585-3590.

  9. Shang P, Qian AR, Yang TH, et al. Experimental study of anti-tumor effects of polysaccharides from Angelica sinensis. World J Gastroenterol. 2003;9(9):1963-1967.

  10. 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.

  11. Deng S, Wang Y, Inui T, et al. Anti-TB polyynes from the roots of Angelica sinensis. Phytother Res. Jul 2008;22(7):878-882.

  12. Hui MK, Wu WK, Shin VY, et al. Polysaccharides from the root of Angelica sinensis protect bone marrow and gastrointestinal tissues against the cytotoxicity of cyclophosphamide in mice. Int J Med Sci. 2006;3(1):1-6.

  13. Xin YF, Zhou GL, Shen M, et al. Angelica sinensis: a novel adjunct to prevent doxorubicin-induced chronic cardiotoxicity. Basic Clin Pharmacol Toxicol. Dec 2007;101(6):421-426.

  14. Xie CH, Zhang MS, Zhou YF, et al. Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-alpha and TGF-beta1 in mice. Oncol Rep. 2006;15(6):1429-1436.

  15. Liu J, Burdette JE, Xu H, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. 2001;49(5):2472-2479.

  16. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause. 2002;9(2):145-150.

  17. 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.

  18. Foster S, Tyler VE. Tyler’s Honest Herbal: A Sensible Guide to the use of Herbs and related remedies. 3rd ed. New York: Haworth Herbal Press; 1993.

  19. DerMarderosian A. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999.

  20. Goh SY, Loh KC. Gynaecomastia and the herbal tonic “Dong Quai”. Singapore Med J. 2001;42(3):115-116.

  21. Page RL, 2nd, Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy. 1999;19(7):870-876.

  22. Chao WW, Lin BF. Bioactivities of major constituents isolated from Angelica sinensis (Danggui). Chin Med. 2011 Aug 19;6:29.

  23. Chen YL, Jian MH, Lin CC, et al. The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma (HCC) cells therapy. Mol Pharmacol. Jun 24 2008.

  24. Lin PC, Chen YL, Chiu SC, et al. Orphan nuclear receptor, Nurr-77 was a possible target gene of butylidenephthalide chemotherapy on glioblastoma multiform brain tumor.J Neurochem. Aug 2008;106(3):1017-1026.

  25. 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. Jul 2008;22(7):923-928.

  26. 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. Jan 1 2008;103(1):195-211.

  27. Tyler V. The Honest Herbal: A Sensible Guide to Herbs and Related Remedies. Philadelphia: George Stickley Company; 1982.

  28. Hirata JD, Swiersz LM, Zell B, Small R, Ettinger B. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril. Dec 1997;68(6):981-986.

  29. Haines CJ, Lam PM, Chung TK, et al. 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 Jun;11(3):244-51.

  30. Friedman JA, Taylor SA, McDermott W, Alikhani P. Multifocal and recurrent subarachnoid hemorrhage due to an herbal supplement containing natural coumarins. Neurocrit Care. 2007;7(1):76-80.

  31. Al-Bareeq RJ, Ray AA, Nott L, Pautler SE, Razvi H. Dong Quai (Angelica sinensis) in the treatment of hot flashes for men on androgen deprivation therapy: results of a randomized double-blind placebo controlled trial. Can Urol Assoc J. 2010 Feb;4(1):49-53.

  32. Bu Y, Kwon S, Kim YT, Kim MY, et al. Neuroprotective effect of HT008-1, a prescription of traditional Korean medicine, on transient focal cerebral ischemia model in rats. Phytother Res. 2010 Feb 10. [Epub ahead of print]

  33. Wong VC, Lim CE, Luo X, Wong WS. Current alternative and complementary therapies used in menopause. Gynecol Endocrinol. 2009 Mar;25(3):166-74.

  34. Liu PJ, Hsieh WT, Huang SH, Liao HF, Chiang BH. Hematopoietic effect of water-soluble polysaccharides from Angelica sinensis on mice with acute blood loss. Exp Hematol. 2010 Jun;38(6):437-45.

  35. Chen MP, Yang SH, Chou CH, et al. The chondroprotective effects of ferulic acid on hydrogen peroxide-stimulated chondrocytes: inhibition of hydrogen peroxide-induced pro-inflammatory cytokines and metalloproteinase gene expression at the mRNA level. Inflamm Res. 2010 Aug;59(8):587-95.

  36. Yu C, Chai X, Yu L, Chen S, Zeng S. Identification of novel pregnane X receptor activators from traditional Chinese medicines. J Ethnopharmacol. 2011 Jun 14;136(1):137-43.

  37. Wen Y, Li J, Tan Y, et al. Angelica sinensis Polysaccharides Stimulated UDP-Sugar Synthase Genes through Promoting Gene Expression of IGF-1 and IGF1R in Chondrocytes: Promoting Anti-Osteoarthritic Activity. PLoS One. 2014 Sep 9;9(9):e107024.

  38. Hook IL. Danggui to Angelica sinensis root: Are potential benefits to European women lost in translation? A review. J Ethnopharmacol. 2014 Feb 27;152(1):1-13.

  39. Wu CT, Lai JN, Tsai YT.The prescription pattern of Chinese herbal products that contain dang-qui and risk of endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan: a population-based study. PLoS One. 2014 Dec 8;9(12):e113887.

  40. Zhang WF, Yang Y, Li X, et al. Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo. Phytomedicine. 2017 Sep 15;33:21-27.

  41. Chiu SC, Chiu TL, Huang SY, et al. Potential therapeutic effects of N-butylidenephthalide from Radix Angelica sinensis (Danggui) in human bladder cancer cells. BMC Complement Altern Med. 2017 Dec 6;17(1):523.

  42. Younas F, Aslam B, Muhammad F, et al. Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats. Pharm Biol. 2017 Dec;55(1):108-113.

  43. Nambiar S, Schwartz RH, Constantino A. Hypertension in mother and baby linked to ingestion of Chinese herbal medicine. West J Med. 1999 Sep;171(3):152.

  44. Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017 Aug 15;32:88-96.