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Astragalus (Astragalus membranaceous)
Astragalus
(Astragalus Synonyms / Common Names / Related Terms
membranaceu
s) Image
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 vira
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
52
 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.
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