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Astragalus (Astragalus membranaceous)


Astragalus (Astragalus membranaceus) Image
Synonyms / Common Names / Related Terms
Astragalosides I-IV, Astragalus gummifera, Astragalus lentiginosus, Astragalus membranaceus, Astragalus membranaceus japonica, Astragalus mollissimus, Astragalus mongholicus, astragalus polysaccharide, Astragalus propinquus, astragalus saponin, Astragalus trigonus, astragel, baak kei, beg kei, bei qi, buck qi, calycosin, Fabaceae (family), formononetin, gaba-aminobytyric acid, goat's horn, goat's thorn, green dragon, gum dragon, gum tragacanthae, gummi tragacanthae, hoang ky, hog gum, Huang Qi, huang-chi, huangoi, huangqi, hwanggi, isoflavonoids, ji cao, Leguminosae (family), locoweed, membranous milk vetch, milk vetch, milkvetch, Mongolian milk, Mongolian milk vetch, neimeng hhuangqi, ogi, ononin, ougi, Phaca membranacea Fisch., radix astragali, spino santo, Syrian tragacanth, tai shen, tragacanth, trigonosides I-III, wong kei, yellow leader, yellow vetch, Zhongfengnaomitong.

Mechanism of Action

Pharmacology:

  • Constituents: Active constituents of astragalus root have been identified and characterized. These components include: polysaccharide cycloartane glycoside fractions (astragalosides I-IV and trigonosides I-III), four major isoflavonoids (formononetin, ononin, calycosin, and its glycoside), saponins, several minor isoflavonoids, and other biogenic amines.25,26,27,28,29,8,30,31 Astragalus also contains triterpenoids. Triterpenoids and saponins have a structural similarity to steroid hormone precursors.
  • Antidiabetic effects: According to animal and human study, saponins, isoflavones and polysaccharides in astragalus can lower blood glucose.24,5,17,32,33,6,7 Based on experimental study, astragaloside IV, a saponin isolated from Astragalus membranaceus, inhibited protein tyrosine phosphorylase and protein kinase C activation, as well as improving F-actin rearrangements, thereby altering insulin sensitivity.30,34 Several investigators have observed increased in vitro cellular uptake of glucose and increased protein synthesis in adipocytes.35,4 Isoflavones in Astragalus membranaceus, including formononectin and biochanin A, were potent activators of both peroxisome proliferator-activated receptors (PPAR) and receptors that are used to restore glycemic balance.33
  • Anti inflammatory effects: The anti-inflammatory activity in vivo may be mediated by inhibition of NF-kappaB activation and mRNA expression.36,37
  • Antimicrobial activity: Astragalus polysaccharides have been shown to induce endogenous interferon production in animals and humans and to potentiate the actions of interferon in viral infections.38,9,22,2 Mice pretreated with astragalus and exposed to Coxsachie B3, Japanese encephalitis virus, NDV, and Sendai viruses have significantly higher interferon levels and macrophage production compared to animals that are not pretreated with astragalus.39,21 Several investigators have reported that mice with viral myocarditis exhibited improvement in overall outcomes and cardiac function, as well as reduced myocardial lesions, viral load, and viral replication in response to astragalus.40,41,20,10,42 Astragalus polysaccharide fractions have also been reported to stimulate the production of IgA, IgM, IgG, and antigen-specific splenocytes in response to bacterial infections in poultry.14,15,16 In contrast, astragalus exhibited no in vitro cytotoxic or antiviral activity against HIV infection.43,39
  • Antineoplastic properties/amelioration of chemotherapy side effects: There is in vitro evidence that astragalus can potentiate the efficacy and reduce the adverse effects of chemotherapy via stimulation of the immune system.18,19,2 Wei et al. reported that astragalus extract significantly increased in vitro cytokine secretion and gene expression in blood mononuclear cells of lung cancer patients.44 Astragalus extracts have been shown to induce LAK cell activity in the lymphocytes of cancer and HIV patients and stimulate the blastogenic response of lymphocytes to mutagens in patients with various cancers.45,46,47,48,49,50 Lau et al. reported that an astragalus-containing herbal combination inhibited tumor growth in vivo while augmenting macrophage and lymphokine-activated killer cell activities.51 Treatment with astragalus-containing herbal remedies also inhibited tumor growth and prolonged survival in rats compared to rats treated with conventional chemotherapy. Other authors have reported the potentiation of interleukin-2 (IL-2)-generated cytotoxicity in animal models45,52 and reduction of mutagenesis53.
  • Antioxidant and cellular protective properties: Astragalus constituents, particularly the flavonoids, exert significant cellular antioxidant effects that appear to be protective against cardiovascular, hepatic, pulmonary, and renal pathological changes.54,55 In vitro, astragalus has been reported to protect against free radical-mediated renal tubular damage induced by high-energy shock waves56 and against radiation injury23. In the hearts of healthy animals and animal models of cardiovascular disease, astragalus polysaccharide and flavonoid fractions have been reported to scavenge mitochondrial free radicals, protect against lipid peroxidation, protect mitochondria from isoproterenol-induced injury, prevent diabetes-induced myocardial hypertrophy, and attenuate pathophysiological decrements in cardiac structure and function in congestive heart failure, diabetes, and experimental hypertension.57,58,59,11,60,61 Astragalus polysaccharide and flavonoid extracts have been shown to preserve kidney function in animal models of renal failure and liver functions in response to hepatotoxins.56,62,63,4,64,65,66 Similarly, astragalus appears to protect cells against hypoxic challenges. Astragaloside IV has been reported to protect human endothelial cells and intestinal epithelial cells against reperfusion injury in vitro following hemorrhagic shock.67 Cellular protection from anoxia has also been observed in cultured neurons68 and in mouse brains after transient focal ischemia69. Astragaloside IV has also inhibited platelet aggregation, decreased plasminogen activation, and facilitated intravascular lysis of fibrin clots in humans and in animal disease models.18,70 In a model of ototoxicity, Xuan et al. reported that astragalus protected cells from pathologic injury via enhanced DNA and RNA synthesis.65 In an animal study, Astragalus membranaceus had preventive and therapeutic potential in experimental colitis.1 The anti-inflammatory actions involved antioxidation along with the inhibition of adhesion molecule synthesis in the colonic tissues. In an in vitro study, astragalus and astragalus saponins potently protected endothelium-dependent relaxation against the acute injury from homocysteine through nitric oxide regulatory pathways, in which antioxidation played a key role.31
  • Cardiovascular effects: Experimental studies indicate that astragalosides affect cardiovascular function at the cellular, isolated tissue, and whole-body levels in both animals and humans. In isolated working rat hearts, Wang et al. reported that astragalus extract produced positive inotropic actions at higher doses and negative inotropic effects at lower doses.52 Astragalus also produces hypotensive actions via peripheral vasodilation in healthy and hypertensive animals.71,72 Chen et al. reported that astragalus significantly reduced arterial pressure in the rat model of renal hypertension and improved cardiac function in experimental congestive heart failure.73 This effect was confirmed by Ma et al. who reported that astragalus improved left ventricular systolic function and potentiated the cardiotonic, diuretic, and natriuretic renal responses to atrial natriuretic peptide in rats with experimentally induced chronic heart failure.13 There is in vitro evidence that astragalus may also stimulate angiogenesis and revascularization in ischemic myocardium66 and amnion74 and promote vascular endothelial cell proliferation and DNA synthesis74. Astragalus has been suggested to increase sodium pump activity in erythrocytes.75
  • Hormonal/reproductive effects: Astragalus has significant effects on various hormonal systems. Astragalosides are reported to significantly increase growth hormone release in rat pituitary cell culture compared to controls.12 Astragalus polysaccharide fractions have also been shown to prevent bone loss in ovariectomized rats.76 In vitro sperm motility and viability have been shown to be significantly increased in healthy rats and men.77 Astragalus has also been reported to inhibit in rats decrements in sperm production and motility caused by cadmium exposure.25 Liu et al. recently reported that astragalus extract significantly increased in vitro sperm motility and viability in 30 infertile men.78
  • Immune system effects: Astragalus flavonoids are reported to increase in vivo cell-mediated immunity in guinea pigs79 and mice42. Astragalus appears to enhance cell-mediated immunity by increasing the number of T-helper cell type 2 cytokines, increasing levels of tumor necrosis factor and interleukin-6.80,81,48,82,83,84 It has been shown to stimulate macrophage and natural killer cell activity.45,85,3 According to animal study, astragalus enhanced both cellular and humoral immune responses to bacterial infections when compared to controls.15 Marrow blood collected from patients with ischemia of the lower limbs and exposed to astragalus had a significantly increased ratio of CD34+ cells (p<0.05).86

Pharmacodynamics/Kinetics:

  • Astragalosides appear to exert their immunomodulatory actions via direct interaction with cellular membrane receptors. Shao et al. reported that astragalus root polysaccharide fractions activated mouse B cells and stimulated macrophage production via direct interaction between the polysaccharide fractions and TLR4 on cell surfaces.35 Hao et al. demonstrated in rat endothelial cells that astragalus root polysaccharide fractions stimulated the adhesion between neutrophils and endothelial cells by promoting the expression of superficial I-1 on the cell surface.87 This action would hypothetically facilitate the inflammatory response in wound healing and possibly underlie the detoxification and cellular protective actions of astragalus polysaccharides observed in several tissues. Astragalus polysaccharides also are known to increase RNA activity and protein synthesis in various tissues and increase the activity of enzymes that regulate specific cellular metabolic functions.2 Astragalus has been shown to modulate ornithine decarboxylase activity and increase insulin-induced protein tyrosine phosphorylase activity in the livers and skeletal muscles of animal models of type 2 diabetes.34
  • There is insufficient available data on the pharmacokinetic parameters for individual chemical constituents of astragalus.

References

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