Astragalus

• Purported Uses
  • To stimulate the immune system
    Laboratory studies suggest that astragalus stimulates the immune system.
  • To reduce severity of chemotherapy side effects, including immune suppression
    Studies in animals show that astragalus reverses immune suppression caused by cyclophosphamide and stimulates certain cells of the immune system. Astragalus may also reduce the side effects of other types of chemotherapy such as nausea, vomiting, and fatigue. In addition, it may enhance the effectiveness of some types of chemotherapies, but these observations need to be confirmed in well-designed human studies.
  • To prevent and treat heart disease
    Lab and animal studies suggest astragalus and its compounds have heart-protective properties as well as blood-thinning effects.
  • To treat diabetes
    Although astragalus has not been specifically studied for this purpose, long-term population studies suggest that it is among several herbs used in Chinese medicine that may improve diabetes-related complications. Clinical trials are needed to confirm such effects.
  • To increase strength and stamina
    An herbal formula containing astragalus reduced fatigue in athletes by increasing uptake and use of oxygen. Another small study showed that a purified astragalus extract infusion may also help manage cancer-related fatigue, but whether an oral formula would work the same way is not known.
• Do Not Take If
  • You are taking immunosuppressants such as tacrolimus and cyclosporine: Astragalus may lessen their effects.
  • You have hormone-sensitive cancer: Because astragalus has demonstrated estrogenic effects, it is unknown how it may affect hormone-sensitive cancers or hormonal chemotherapy.
  • You are undergoing cancer treatment: Laboratory studies suggest that certain properties of astragalus might interfere with the effectiveness of some types of cancer treatment.
  • You are taking anticoagulants: Lab studies suggest that astragalus may increase bleeding risk.
  • You are undergoing surgery: Lab studies suggest that astragalus may increase bleeding risk.
  • You are taking diuretic medications: A small study suggests that astragalus may increase their effects.
  • You are taking blood pressure medications: Astragalus may increase the blood pressure-lowering effect.
• Side Effects

  Fatigue, unease, and headache were reported in a study.

• Scientific Name

  Astragalus membranaceus

• Clinical Summary

  Astragalus belongs to a group of medicinal plants from the Leguminosae family. The root of A. membranaceus has a long history of use in traditional Chinese medicine (TCM), and is often used along with other herbs as a tonic to increase stamina, strength, and vitality. Extracts of astragalus are sold as dietary supplements to improve immune function and to decrease fatigue. Beneficial effects of astragalus are attributed to its polysaccharides and triterpenoid saponin compounds. In vitro and animal studies indicate that astragalus and its constituents have antioxidant ⁽²⁷⁾, anti-inflammatory ⁽²⁸⁾, and antiviral ⁽²⁹⁾ activities, along with exerting protective effects on heart ^{(30) (31) (32)}, kidney ^{(33) (34) (35)}, bones ⁽³⁶⁾ , and the nervous system ^{(11) (17) (37)}.

  In small studies involving healthy individuals, astragalus exhibited sodium-excreting properties ⁽⁸⁾ and produced a viral-type immune response ⁽³⁸⁾. A formula containing astragalus as a major ingredient reduced fatigue in athletes ⁽¹⁰⁾. Used as an injection, astragalus may benefit patients with IgA nephropathy ⁽²⁶⁾, and when used in Chinese medicine, it helped reduce diabetic ketoacidosis ⁽³⁹⁾. In dialysis patients, an astragalus-based TCM formula was shown to preserve residual renal function ⁽⁴⁰⁾. A case report suggests that it may reduce proteinuria associated with idiopathic membranous nephropathy ⁽⁷⁾, and a systematic review concluded that adjunctive use of astragalus in addition to conventional therapies may be effective for short-term reductions of albuminuria, proteinuria, and serum creatinine in patients with diabetic kidney disease ⁽⁶⁰⁾.

  Anticancer properties have been observed as well against gastric ⁽⁴¹⁾, colon ^{(42) (43) (44) (45)}, hepatic ⁽⁴⁶⁾ and ovarian ⁽⁵⁹⁾ cancers. Astragalus has also been associated with prolonged survival times in acute myeloid leukemia patients ⁽⁴⁷⁾, and data suggest beneficial effects when used with chemotherapy ^(1) (2). In vitro, concomitant treatment with aldesleukin and astragalus potentiated tumoricidal activity while decreasing side effects ⁽¹⁴⁾. Astragalus also enhanced platinum-based chemotherapy ⁽³⁾ and protected against oxaliplatin neurotoxicity ⁽⁴⁸⁾. Its saponins were shown to reverse toxicities of fluorouracil ^(42) (28) and augmented the therapeutic benefit of vinblastine while reducing neutropenic and anemic effects in vivo ⁽⁴⁴⁾.
  An injectable form of astragalus with vinorelbine and cisplatin improved quality of life in patients with advanced non-small cell lung cancer ⁽²⁰⁾, but whether orally administered astragalus would exert similar effects is not known. In another study, an astragalus extract helped to manage cancer-related fatigue ⁽²²⁾. Meta-analyses suggest astragalus to be associated with reductions in chemotherapy-induced nausea and vomiting ⁽⁴⁹⁾, and to have benefits in patients with hepatocellular cancers ⁽¹⁶⁾. Larger well-designed trials are needed to confirm these findings.

  Although astragalus is generally safe, due to its antioxidant ⁽²⁷⁾ and estrogenic ^(23) (50) activities, it may interfere with some chemotherapy drugs and/or affect hormone-sensitive cancers. However, these findings are based on preclinical studies and cannot be extrapolated to clinical recommendations. The physiological concentration used in these studies is unlikely to be achieved in humans, which makes it difficult to predict the downstream effects/interactions.

• Purported Uses
  • Cardiovascular disease
  • Chemotherapy side effects
  • Diabetes
  • Immunostimulation
  • Microbial infection
  • Strength and stamina
• Mechanism of Action

  Polysaccharides, triterpenoid saponins, and flavonoids are the main constituents of astragalus with immunomodulating, antioxidant, anti-inflammatory, and anticancer effects ^(27) (51). In vitro studies suggest the saponin astragaloside I promotes osteoblastic differentiation by regulating the Wnt/beta-catenin signaling pathway ⁽³⁶⁾. Cardioprotective effects from astragaloside IV may occur via the notch1/hes1 signaling pathway ⁽³⁰⁾. In addition, it augments fibrinolytic potential via increases in tissue-type plasminogen activator (t-PA) synthesis and downregulation of PA inhibitor type 1 (PAI-1) ⁽²¹⁾. Other anticoagulant activities are attributed to upregulation of KLF2 mRNA expression and inhibition of NF-kB signaling pathway ⁽⁵²⁾.

  Polysaccharides isolated from astragalus produce immunomodulating effects via activation of toll-like receptor 4 (TLR4)-related mitogen-activated protein kinase (MAPK) activities ⁽⁵³⁾. In murine models, they reduced colitis via inhibition of NOD-like receptor protein 3 inflammasome, which decreases inflammatory factors such as interleukin (IL)-18 and IL-1beta ⁽⁵⁴⁾, and reduced multiorgan iron overload via upregulated hepcidin and IL-6 expression and enhanced p38 MAPK phosphorylation ⁽⁵⁵⁾. Cardioprotective effects with this constituent were attributed to anti-inflammatory properties and improved balance between reactive oxygen species (ROS) and NO ⁽³²⁾. In a diabetic rat model, astragalus polysaccharides exerted effects on glucose and lipid metabolism and insulin resistance ⁽³⁷⁾. Astragalus was also found to reduce the secretion of inflammatory cytokines via increasing levels of CD4⁺ CD25⁺ Foxp3⁺ T cells and by inhibiting the activation of NF-κB ⁽⁶¹⁾.

  Benefits to counteract memory disorders were seen with astragalus due to its activity as a nerve-growth promoting factor ⁽¹⁷⁾ and due to its ability to increase M-cholinergic receptor density in senile rats ⁽¹¹⁾.

  In dialysis patients, an astragalus-based TCM formula enhanced NO production and transforming growth factor beta suppression ⁽⁴⁰⁾. In IgA nephropathy patients, an astragalus injection decreased Core I β3-Gal-T-specific molecular chaperone (Cosmc) gene expression and increased IgA1 O-glycosylation levels ⁽²⁶⁾. In healthy individuals, a sublingual/ingested astragalus root extract produced increases in monocytes, neutrophils, lymphocytes, and platelets, as well as circulating cytokines levels, and self-reported symptoms similar to viral type immune responses such as fatigue, malaise, and headache ⁽³⁸⁾. In another study, a formula containing astragalus reduced fatigue in athletes by increasing the uptake and utility of oxygen ⁽¹⁰⁾.

  Mechanisms by which astragalus and its constituents may exert anticancer effects have also been examined. In human colorectal cancers cell lines, astragalus suppressed chromosome organization, histone modification, and regulation of macromolecule metabolism, as well as several cancer signaling pathways ⁽⁵⁶⁾. Saponins induced S phase and G2/M arrest and suppressed p21 expression and cyclin-dependent kinase activity ⁽⁴²⁾. Modulation of mTOR signaling and COX2 downregulation also occurred, which in turn can reduce VEGF levels to suppress angiogenesis ⁽⁴³⁾. In gastric adenocarcinoma cells, caspase 3 activation, G2/M phase cell cycle arrest, cyclin B1, p21 and c-myc regulation, and downregulation of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP)-2 and MMP-9 occurred ⁽⁴¹⁾. Combined with vinblastine, saponins boosted downregulation of proangiogenic and proliferative factors while attenuating neutropenia and anemia seen with this chemotherapy ⁽⁴⁴⁾. In combination with calpain inhibitors, these saponins may also exert more pronounced apoptotic effects ⁽⁴⁵⁾. Polysaccharides potentiate immune-mediated antitumor activity of interleukin-2 in vitro ⁽¹³⁾, improve lymphocyte responses, enhance natural killer cell activity, potentiate monocyte activity ⁽¹⁴⁾, increase phagocytosis perhaps by regulating tumor necrosis factor production ⁽⁵⁾, and activate macrophages to release nitric oxie and tumor necrosis factor-alpha, which directly blocks growth of breast cancer cells ⁽⁶²⁾. Apoptotic effects by polysaccharides in hepatocellular carcimona cells were attributed to decreased Notch1 expression ⁽⁴⁶⁾.

  Formononetin derived from astragalus was shown to have estrogen-receptor-modulating effects ⁽⁵⁰⁾. Angiogenic effects of astragaloside IV appear to be synergized when combined with ferulic acid from Angelica sinsensis ⁽⁵⁷⁾.

• Adverse Reactions

  Fatigue, malaise, headache, and lowering of blood pressure have been reported (38)

• Herb-Drug Interactions
  • Immunosuppressants: Theoretically, astragalus may antagonize the effects of immunosuppressants such as tacrolimus and cyclosporine.
  • Hormonal therapies: Astragalus and its constituents have estrogenic ^(23) (50) properties and may interfere with their actions.
  • Anticoagulants: In vitro studies suggest that astragalus and its constituents have anticoagulant properties ⁽⁵²⁾, which may increase bleeding risk when used with these drugs.
  • Diuretics: In a small study, astragalus was shown to have natriuretic effects ⁽⁸⁾ and may therefore have additive effects with these medications.
  • Antihypertensive drugs: Astragalus extract can lower both systolic and diastolic blood pressure and may have additive effects with other antihypertensive drugs ⁽³⁸⁾.
  • P-glycoprotein substrates: Astragalus polysaccharides can inhibit P-glycoprotein efflux pump function. This may increase the cytotoxicity of chemotherapy drugs, including doxorubicin, etoposide, and vincristine ⁽⁵⁸⁾.
  • Gemcitabine: Pretreatment with an astragalus extract was found to affect pharmacokinetics of gemcitabine in a murine model. Clinical relevance is not known ⁽⁶³⁾.
• References

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  2. Taixiang W, Munro AJ, Guanjian L. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004540.

  3. McCulloch M, See C, Shu XJ, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials. J Clin Oncol. 2006 Jan 20;24(3):419-30.

  4. Cui R, He J, Wang B, et al. Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemother Pharmacol. 2003 Jan;51(1):75-80.

  5. Cho WC, Leung KN. In vitro and in vivo anti-tumor effects of Astragalus membranaceus.Cancer Lett. Jul 8 2007;252(1):43-54.

  6. Yu L, Lu Y, Li J, Wang H. Identification of a gene associated with astragalus and angelica’s renal protective effects by silver staining mRNA differential display. Chin Med J (Engl) 2002;115:923-7.

  7. Ahmed MS, Hou SH, Battaglia MC, et al. Treatment of idiopathic membranous nephropathy with the herb Astragalus membranaceus. Am J Kidney Dis. Dec 2007;50(6):1028-1032.

  8. Ai P, Yong G, Dingkun G, et al. Aqueous extract of Astragali Radix induces human natriuresis through enhancement of renal response to atrial natriuretic peptide. J Ethnopharmacol. Mar 28 2008;116(3):413-421.

  9. Shen HH, Wang K, Li W, et al. Astragalus membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition.J Ethnopharmacol. Mar 5 2008;116(2):363-369.

  10. Chen KT, Su CH, Hsin LH, et al. Reducing fatigue of athletes following oral administration of huangqi jianzhong tang. Acta Pharmacol Sin. 2002 Aug;23(8):757-61.

  11. Shi R, He L, Hu Y, et al. The regulatory action of radix astragali on M-cholinergic receptor of the brain of senile rats. J Tradit Chin Med 2001;21:232-5.

  12. Tang W, et al. Chinese Drugs of Plant Origin. Berlin: Springer-Verlag; 1992.

  13. Qun L, Luo Q, Zhang ZY, et al. Effects of astragalus on IL-2/IL-2R system in patients with maintained hemodialysis. Clin Nephrol. 1999 Nov;52(5):333-4.

  14. Chu DT, Lepe-Zuniga J, Wong WL, et al. Fractionated extract of Astragalus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2. J Clin Lab Immunol 1988;26:183-7.

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  16. Wu P, Dugoua JJ, Eyawo O, Mills EJ. Traditional Chinese medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis. J Exp Clin Cancer Res. 2009 Aug 12;28(1):112.

  17. Lu MC, Yao CH, Wang SH, et al. Effect of Astragalus membranaceus in rats on peripheral nerve regeneration: in vitro and in vivo studies. J Trauma. 2010 Feb;68(2):434-40.

  18. Wojcikowski K, Wohlmuth H, Johnson DW, Gobe G. Effect of Astragalus membranaceus and Angelica sinensis combined with Enalapril in rats with obstructive uropathy. Phytother Res. 2010 Jun;24(6):875-84.

  19. Auyeung KK, Woo PK, Law PC, Ko JK. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol. 2012;141(2):635-41.

  20. Guo L, Bai SP, Zhao L, Wang XH. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival. Med Oncol. 2012;29(3):1656-62.

  21. Zhang WJ, Wojta J, Binder BR. Regulation of the fibrinolytic potential of cultured human umbilical vein endothelial cells: astragaloside IV downregulates plasminogen activator inhibitor-1 and upregulates tissue-type plasminogen activator expression. J Vasc Res. 1997 Jul-Aug;34(4):273-80.

  22. 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 Feb 1;35(1):E1-11.

  23. Zhang CZ, Wang SX, Zhang Y, Chen JP, Liang XM. In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J Ethnopharmacol. 2005 Apr 26;98(3):295-300.

  24. Fu J, Wang Z, Huang L, et al. Review of the Botanical Characteristics, Phytochemistry, and Pharmacology of Astragalus membranaceus (Huangqi). Phytother Res. 2014 Sep;28(9):1275-83.

  25. Xu X, Li F, Zhang X, et al. In vitro synergistic antioxidant activity and identification of antioxidant components from Astragalus membranaceus and Paeonia lactiflora. PLoS One. 2014 May 9;9(5):e96780. doi: 10.1371/journal.pone.0096780. eCollection 2014.

  26. Ji L, Chen X, Zhong X, et al. Astragalus membranaceus up-regulate Cosmc expression and reverse IgA dys-glycosylation in IgA nephropathy. BMC Complement Altern Med. 2014 Jun 18;14:195. doi: 10.1186/1472-6882-14-195.

  27. Shahzad M, Shabbir A, Wojcikowski K, et al. The Antioxidant Effects of Radix Astragali (Astragalus membranaceus and Related Species) in Protecting Tissues from Injury and Disease. Curr Drug Targets. 2016;17(12):1331-1340.

  28. Wang Y, Ren T, Zheng L, et al. Astragalus saponins Inhibits Lipopolysaccharide-Induced Inflammation in Mouse Macrophages. Am J Chin Med. 2016;44(3):579-593.

  29. Wang S, Li J, Huang H, et al. Anti-hepatitis B virus activities of astragaloside IV isolated from radix Astragali. Biol Pharm Bull. Jan 2009;32(1):132-135.

  30. Huang H, Lai S, Wan Q, et al. Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein. Can J Physiol Pharmacol. May 2016;94(5):542-553.

  31. Hu JY, Han J, Chu ZG, et al. Astragaloside IV attenuates hypoxia-induced cardiomyocyte damage in rats by upregulating superoxide dismutase-1 levels. Clin Exp Pharmacol Physiol. Apr 2009;36(4):351-357.

  32. Han R, Tang F, Lu M, et al. Protective effects of Astragalus polysaccharides against endothelial dysfunction in hypertrophic rats induced by isoproterenol. Int Immunopharmacol. Sep 2016;38:306-312.

  33. Shan G, Zhou XJ, Xia Y, et al. Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting tubular epithelial-mesenchymal transition in vivo and in vitro. Exp Ther Med. May 2016;11(5):1611-1616.

  34. Shahzad M, Small DM, Morais C, et al. Protection against oxidative stress-induced apoptosis in kidney epithelium by Angelica and Astragalus. J Ethnopharmacol. Feb 17 2016;179:412-419.

  35. Meng LQ, Tang JW, Wang Y, et al. Astragaloside IV synergizes with ferulic acid to inhibit renal tubulointerstitial fibrosis in rats with obstructive nephropathy. Br J Pharmacol. Apr 2011;162(8):1805-1818.

  36. Cheng X, Wei B, Sun L, et al. Astragaloside I Stimulates Osteoblast Differentiation Through the Wnt/beta-catenin Signaling Pathway. Phytother Res. Jul 10 2016.

  37. Dun C, Liu J, Qiu F, et al. Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model. Neuropsychiatr Dis Treat. 2016;12:1617-1621.

  38. Denzler K, Moore J, Harrington H, et al. Characterization of the Physiological Response following In Vivo Administration of Astragalus membranaceus. Evid Based Complement Alternat Med. 2016;2016:6861078.

  39. Lien AS, Jiang YD, Chih-Hsin Mou MS, et al. Integrative Traditional Chinese Medicine Therapy Reduces the Risk of Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus. J Ethnopharmacol. Jun 20 2016.

  40. Lui SL, Zhu D, Cheng SW, et al. Effects of Astragalus membranaceus-based Chinese Medicine Formulae on Residual Renal Function in Patients on Peritoneal Dialysis. Perit Dial Int. Sep-Oct 2015;35(5):595-597.

  41. Auyeung KK, Woo PK, Law PC, et al. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol. Jun 1 2012;141(2):635-641.

  42. Tin MM, Cho CH, Chan K, et al. Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis. Jun 2007;28(6):1347-1355.

  43. Law PC, Auyeung KK, Chan LY, et al. Astragalus saponins downregulate vascular endothelial growth factor under cobalt chloride-stimulated hypoxia in colon cancer cells. BMC Complement Altern Med. 2012;12:160.

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  45. Wang Y, Auyeung KK, Zhang X, et al. Astragalus saponins modulates colon cancer development by regulating calpain-mediated glucose-regulated protein expression. BMC Complement Altern Med. 2014;14:401.

  46. Huang WH, Liao WR, Sun RX. Astragalus polysaccharide induces the apoptosis of human hepatocellular carcinoma cells by decreasing the expression of Notch1. Int J Mol Med. Aug 2016;38(2):551-557.

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  53. Wei W, Xiao HT, Bao WR, et al. TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells. J Ethnopharmacol. Feb 17 2016;179:243-252.

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  55. Ren F, Qian XH, Qian XL. Astragalus polysaccharide upregulates hepcidin and reduces iron overload in mice via activation of p38 mitogen-activated protein kinase. Biochem Biophys Res Commun. Mar 25 2016;472(1):163-168.

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  57. Wang H, Zhang Y, Xia T, et al. Synergistic promotion of blood vessel regeneration by astragaloside IV and ferulic acid from electrospun fibrous mats. Mol Pharm. Jun 3 2013;10(6):2394-2403.

  58. Tian QE, De Li H, Yan M, et al. Effects of Astragalus polysaccharides on P-glycoprotein efflux pump function and protein expression in H22 hepatoma cells in vitro. BMC Complement Altern Med. 2012 Jul 11;12:94. doi: 10.1186/1472-6882-12-94.

  59. Zhang J, Liu L, Wang J, Ren B, Zhang L, Li W. Formononetin, an isoflavone from Astragalus membranaceus inhibits proliferation and metastasis of ovarian cancer cells. J Ethnopharmacol. 2018 Jul 15;221:91-99.

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