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⁾.