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Astragalus

Scientific Name(s): Astragalus membranaceus (Moench), Astragalus mongholicus Bunge.
Common Name(s): Astragalus, Huáng chí, Huáng qí, Hwanggi, Jin Fu Kang, Membranous milk-vetch, Meng gu huang qi, Ogi, Ougi, Radix Astragali

Clinical Overview

Use

Most evidence suggests that astragalus root may modulate immune function and reported benefits are derived from this action, although studies are older and of limited quality. Evidence in the literature for other purported therapeutic uses is lacking.

Dosing

There is no recent clinical evidence to guide dosage of astragalus products; however, recommendations of 2 to 6 g daily of the powdered root are typical.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Allergy has been reported. A case report exists of increased carbohydrate antigen 19-9 and induction of reversible liver and kidney cysts in a woman consuming A. membranaceus daily for 1 month.

Toxicology

Evidence is equivocal; however, mutagenicity has been shown in the Ames test.

Botany

The genus Astragalus, commonly known as milk vetches, comprises more than 2,000 species distributed worldwide. The perennial herbs grow to approximately 1 m high, are native to the northern provinces of China, and are cultivated in China, Korea, and Japan. The plants bear tubular yellowish flowers and small (3 to 6 cm) leaves. The dried root harvested from mature plants 4 to 7 years old is used medicinally and sold as 15 to 20 cm pieces with a tough, fibrous skin and a light interior.1, 2, 3, 4

History

Astragalus root is well known in traditional Chinese medicine and is listed in the Pharmacopoeia of the People's Republic of China. It is an important component of Chinese Fu Zheng herbal therapy, in which the goal is to restore immune system function by reinforcing the body’s Qi, and is principally used as a tonic and for treatment of diabetes and nephritis. There is extensive Chinese-language literature on the herb/plant. It is sold as shredded roots and in powder, tincture, and encapsulated form. Some products are produced by frying the roots with honey and the untreated root has a sweet, licorice-like taste of its own. Astragalus root is used in the United States as an immunostimulant to counteract the immune suppression associated with cancer chemotherapy.1, 2, 3, 4

Chemistry

Compounds identified in astragalus include polysaccharides, saponins, flavonoids, isoflavonoids, sterols, amino acids (including gamma-aminobutyric acid), volatile oils, and other mineral elements (eg, zinc, iron, copper, manganese, vanadium, tin).

The polysaccharides include the astragalans and astraglucans and are of primary interest along with the triterpene saponin astragalosides. The flavones kaempferol and quercetin and isoflavones, isoflavonones, and pterocarpans are also of interest. The saponin astragaloside intravenous (IV) has been used as a marker for quality assurance of astragalus products.3, 5, 6, 7

Uses and Pharmacology

Cancer

Clinical data

Astragalus root as adjunctive therapy in cancer has been studied in limited Chinese trials, including a combination preparation (Jin Fu Kang) used in China for the treatment of non–small cell lung cancer, and IV astragalus in malignant tumor.8, 9, 10 An IV extract (PG2) from A. membranaceus has been studied for cancer-related fatigue in an open-label study, which found improvements in subjective outcomes.11

A systematic review of herbal medicines as adjuvants to the leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX-4) regimen used for treating colorectal cancer was conducted to identify evidence of safety and efficacy of treatment, as well as management of chemotherapy adverse reactions. A total of 13 randomized Chinese clinical trials involving 940 patients compared herbal medicines plus the FOLFOX-4 combination with the FOLFOX-4 regimen alone in patients with advanced (stage IV) colorectal cancer. Although 58 different herbs and/or extracts were used in 7 studies, A. membranaceus was the most common herb found in treatment preparations. Tumor response rate, overall survival at 1 year, time to progression, quality of life, body weight, nausea/vomiting symptoms, and neutropenia improved significantly (P values from P < 0.00001 to P = 0.01) with herbal adjuvants. Astragalus was included in each of the studies contributing to these results.12

Cardiovascular

Animal data

Contractility improved in isolated frog and toad hearts, and extracts produced hypotension in cats, dogs, and rabbits. Saponins from astragalus exerted positive inotropic activity in isolated rat heart tissue.3 Astragalosides also increased fibrinolytic potential in human umbilical vein tissue with effects on plasminogen expression.13

Clinical data

No clinical reports of interference with hemostasis have been published.13 Astragalus has been studied in Chinese clinical trials using patients with cardiopulmonary bypass, ischemic heart disease, angina pectoris, and chronic heart failure with positive effect.14, 15, 16, 17 No effect of astragalus has been found in improving clinical outcomes in viral myocarditis, and the quality of those studies included in the Cochrane review was reported to be poor.18

Immune effects

In vitro and animal data

Several studies on immune function have been conducted in rodents and in vitro using human cells.19, 20, 21, 22, 23, 24, 25, 26

Clinical data

A number of clinical trials have been conducted in Chinese populations with immune-related conditions including systemic lupus erythematosus, myasthenia gravis, and herpes simplex keratitis. Although the studies were small and published in Chinese, findings were generally supportive of enhanced immune function as demonstrated by indices of cytokines or other relevant measures.27, 28, 29, 30, 31 Other clinical studies have been published reporting effects of the extract on long-term fatigue (astragalus in combination), and cancer-related fatigue with improvements in subjective outcomes, but not cytokine expression.11, 32 T cell activation by A. membranaceus has been reported in healthy volunteers given the extract orally.33

Astragalus has been studied in viral diseases including HIV, herpes simplex, and coxsackie-B infections as adjunctive therapy, most likely due to immune effects rather than direct action on a virus itself. T cell responses to A. membranaceus in patients with viral myocarditis reflected an enhanced immune response; however, no reduction in deaths due to cardiac failure was shown.18 Initial interest in the extract for a therapeutic role in HIV treatment34, 35, 36 has not persisted, with no further clinical trials reported.

Other uses

Diabetes

Studies in rodents suggest potential applications of A. membranaceus in diabetes. A small clinical study in type 2 diabetes showed improvements in glucose metabolism, but not other glycemic indices.6, 37

Renal effects

Natriuretic activity of oral Radix Astragali has been demonstrated in healthy adult men.38 Chinese studies have demonstrated effects on kidney function, including reducing proteinuria in chronic kidney disease; however, methodologies have varied, and solid evidence for efficacy has not been determined.7, 39

Other

Astragaloside IV has been shown to promote the repair of sciatic nerve injury in a rodent study.40 Although astragalus is often recommended for prevention of the common cold, there are no published English-language clinical trials that support this use. Antioxidant properties and a wide range of other effects have been demonstrated in limited studies.

Dosing

There is no recent clinical evidence to guide dosage of astragalus products; however, recommendations of 2 to 6 g daily of the powdered root are typical.3, 41

The saponin astragaloside IV has been used as a marker for quality assurance of astragalus products, but is not considered a major bioactive constituent.7

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Although clinically important case reports are lacking, potentiation of acyclovir and related compounds of interleukin and interferon and suppression of immunosuppressant medicines could occur. Potentiation of thrombolytics may also be possible.13

Adverse Reactions

Allergy has been reported.7 A case report exists of increased carbohydrate antigen 19-9 and induction of reversible liver and kidney cysts in a woman consuming A. membranaceus daily for 1 month.42

Toxicology

An astragalus hot water extract was mutagenic in the Ames test in Salmonella typhimurium TA98 when activated by S9 rat liver fractions. The same preparations given by intraperitoneal injection at 1 to 10 g/kg produced chromosomal aberrations in the bone marrow of mice and increased the incidence of micronucleated cells in bone marrow. No attempt was made to isolate the mutagenic compounds responsible for these effects.43 Other tests suggest astragalus to be antimutagenic.3 At doses 100 times higher than effective oral doses in humans, no adverse effects were observed in mice, while a median lethal dose for intraperitoneal administration of 40 g/kg in mice has been reported.3

References

1. Tang W, Eisenbrand, G. Chinese Drugs of Plant Origin. Berlin: Springer-Verlag; 1992:191.
2. Khan IA, Abourashed EA. Leung's Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 3rd ed. Hoboken, NJ: Wiley; 2009.
3. Radix Astragali. In: WHO Monographs on Selected Medicinal Plants. Vol 1. Geneva, Switzerland: World Health Organization; 1999. http://apps.who.int/medicinedocs/en/d/Js2200e/7.html
4. Fu J, Wang Z, Huang L, et al. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother Res. 2014;28(9):1275-1283.25087616
5. Duke JA. Handbook of Medicinal Herbs, 2nd ed. Boca Raton, FL: CRC Press; 2003.
6. Agyemang K, Han L, Liu E, Zhang Y, Wang T, Gao X. Recent advances in Astragalus membranaceus anti-diabetic research: pharmacological effects of its phytochemical constituents. Evid Based Complement Alternat Med. 2013;2013:654643.24348714
7. Zhang HW, Lin ZX, Xu C, Leung C, Chan LS. Astragalus (a traditional Chinese medicine) for treating chronic kidney disease. Cochrane Database Syst Rev. 2014;10:CD008369.25335553
8. Cassileth BR, Rizvi N, Deng G, et al. Safety and pharmacokinetic trial of docetaxel plus an Astragalus-based herbal formula for non-small cell lung cancer patients. Cancer Chemother Pharmacol. 2009;65(1):67-71.19421753
9. Duan P, Wang ZM. Clinical study on effect of Astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002;22(7):515-517.12592686
10. Zou YH, Liu XM. Effect of astragalus injection combined with chemotherapy on quality of life in patients with advanced non-small cell lung cancer [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003;23(10):733-735.14626183
11. Chen HW, Lin IH, Chen YJ, et al. A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Clin Invest Med. 2012;35(1):E1-11.22309959
12. Chen M, May BH, Zhou IW, Xue CC, Zhang AL. FOLFOX 4 combined with herbal medicine for advanced colorectal cancer: a systematic review. Phytother Res. 2014;28(7):976-991.24343974
13. Stargrove MB, Treasure J, McKee DL. Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies. St. Louis, MO:Mosby; 2008.
14. Qu ZL, Dong H, Wang SD. Effects of astragalus injection on renal function in patients after cardiac valve replacement with cardiopulmonary bypass [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009;29(4):313-316.19526755
15. Yang QY, Lu S, Sun HR. Effects of astragalus on cardiac function and serum tumor necrosis factor-alpha level in patients with chronic heart failure [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010;30(7):699-701.20929124
16. Zhang JG, Yang N, He H. Effect of astragalus injection on serum apoptosis relevant factors in patients with chronic heart failure [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2005;25(5):400-403.15957829
17. Dai H, Jia G, Liu X, Liu Z, Wang H. Astragalus polysaccharide inhibits isoprenaline-induced cardiac hypertrophy via suppressing Ca2+mediated calcineurin/NFATc3 and CaMKII signaling cascades. Environ Toxicol Pharmacol. 2014;38(1):263-271.24975447
18. Liu ZL, Liu ZJ, Liu JP, Kwong JS. Herbal medicines for viral myocarditis. Cochrane Database Syst Rev. 2013;8:CD003711.23986406
19. Chen SM, Tsai YS, Lee SW, et al. Astragalus membranaceus modulates Th1/2 immune balance and activates PPARγ in a murine asthma model. Biochem Cell Biol. 2014;92(5):397-405.25264079
20. Calis I, Yürüker A, Tasdemir D, et al. Cycloartane triterpene glycosides from the roots of Astragalus melanophrurius. Planta Med. 1997;63(2):183-186.9140236
21. Liu X, Wang M, Wu H, Zhao X, Li H. Isolation of astragalan and its immunological activities. Tianran Chanwu Yanjiu Yu Kaifa. 1994;6:23-31.
22. Tomoda M, Shimizu N, Ōhara N, Gonda R, Ishii S, Ōtsuki H. A reticuloendothelial system-activating glycan from the roots of Astragalus membranaceus. Phytochemistry. 1991;31:63-66.
23. Shimizu N, Tomoda M, Kanari M, Gonda R. An acidic polysaccharide having activity on the reticuloendothelial system from the root of Astragalus mongholicus. Chem Pharm Bull (Tokyo). 1991;39(11):2969-2972.1799943
24. Sun Y, Hersh E, Lee SL, McLaughlin M, Loo T, Mavligit G. Preliminary observations on the effects of the Chinese medicinal herbs Astragalus membranaceus and Ligustrum lucidum on lymphocyte blastogenic responses. J Biol Response Mod. 1983;2(3):227-237.6644339
25. Lau BH, Ong P, Tosk J. Macrophage chemiluminescence modulated by Chinese medicinal herbs Astragalus membranaceus and Ligustrum lucidum. Phytother Res. 1989;3:148.
26. Sun Y, Hersh E, Talpaz M, et al. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer. 1983;52(1):70-73.6336578
27. Cai XY, Xu YL, Lin XJ. Effects of radix Astragali injection on apoptosis of lymphocytes and immune function in patients with systemic lupus erythematosus [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006;26(5):443-445.16883914
28. Mao SP, Cheng KL, Zhou YF. Modulatory effect of Astragalus membranaceus on Th1/Th2 cytokine in patients with herpes simplex keratitis [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004;24(2):121-123.15015443
29. Niu GH, Sun X, Zhang CM. Effect of compound astragalus recipe on lymphocyte subset, immunoglobulin and complements in patients with myasthenia gravia [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009;29(4):305-308.19526753
30. Su L, Mao JC, Gu JH. Effect of intravenous drip infusion of cyclophosphamide with high-dose Astragalus injection in treating lupus nephritis [in Chinese]. Zhong Xi Yi Jie He Xue Bao. 2007;5(3):272-275.
31. Yang HY, Li J, Yi M. Study on chronical hepatitis B with treatment of integrative traditional Chinese and Western medicine [in Chinese]. Zhongguo Zhong Yao Za Zhi. 2006;31(15):1277-1280.17048576
32. Cho JH, Cho CK, Shin JW, Son JY, Kang W, Son CG. Myelophil, an extract mix of Astragali Radix and Salviae Radix, ameliorates chronic fatigue: a randomised, double-blind, controlled pilot study. Complement Ther Med. 2009;17(3):141-146.19398067
33. Brush J, Mendenhall E, Guggenheim A, et al. The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans. Phytother Res. 2006;20(8):687-695.16807880
34. Yao XJ, Wainberg M, Parniak M. Mechanism of inhibition of HIV-1 infection in vitro by purified extract of Prunella vulgaris. Virology. 1992;187(1):56-62.1371029
35. Ono K, Nakane H, Meng ZM, Ose Y, Sakai Y, Mizuno M. Differential inhibitory effects of various herb extracts on the activities of reverse transcriptase and various deoxyribonucleic acid (DNA) polymerases. Chem Pharm Bull (Tokyo). 1989;37(7):1810-1812.2478305
36. Burack JH, Cohen MR, Hahn JA, Abrams DI. Pilot randomized controlled trial of Chinese herbal treatment for HIV-associated symptoms. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12(4):386-393.8673548
37. Chao M, Zou D, Zhang Y, et al. Improving insulin resistance with traditional Chinese medicine in type 2 diabetic patients. Endocrine. 2009;36(2):268-274.19728183
38. Ai P, Yong G, Dingkun G, Qiuyu Z, Kaiyuan Z, Shanyan L. Aqueous extract of Astragali Radix induces human natriuresis through enhancement of renal response to atrial natriuretic peptide. J Ethnopharmacol. 2008;116(3):413-421.18243612
39. Zhang J, Xie X, Li C, Fu P. Systematic review of the renal protective effect of Astragalus membranaceus (root) on diabetic nephropathy in animal models. J Ethnopharmacol. 2009;126(2):189-196.19735713
40. Zhang X, Chen J. The mechanism of astragaloside IV promoting sciatic nerve regeneration. Neural Regen Res. 2013;8(24):2256-2265.25206535
41. Gruenwald J, ed. PDR for Herbal Medicines. 2nd ed. Montvale, NJ: Thomson Healthcare Inc; 2000:56.
42. Tong X, Xiao D, Yao F, Huang T. Astragalus membranaceus as a cause of increased CA19-9 and liver and kidney cysts: a case report. J Clin Pharm Ther. 2014;39(5):561-563.24806627
43. Yin XJ, Liu DX, Wang HC, Zhou Y. A study on the mutagenicity of 102 raw pharmaceuticals used in Chinese traditional medicine. Mutat Res. 1991;260(1):73-82.2027343

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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