Abstract
Astragalus membranaceus (AM) is a traditionally used medicinal herb in Asia for the treatment of diabetes. Recent studies have shown that the extracts from AM roots exert anti‐diabetic effects in animals and humans, however the major bioactive constituents and the potential mechanism by which AM improves insulin sensitivity still remains unclear. Here, we investigated the effect of formononetin, a major bioactive compound isolated from AM, on adipocyte differentiation and insulin sensitivity in C3H10T1/2 pluripotent mesenchymal stem cells. Formononetin at 1 to 20µM concentrations dose‐dependently enhanced adipocyte differentiation, consistent with increased expression of PPARγ and C/EBPα proteins. Formononetin also markedly induced the expression of PPARγ target genes such as fatty acid binding protein 4 (FABP4) and GLUT4 proteins. In addition, formononetin treatment significantly increased glucose uptake as well as the expression of insulin receptor substrate‐1 (IRS‐1), a key molecule for insulin signaling and action. Moreover, the effects of formononetin on differentiation and PPARγ expression were blunted in the presence of PPARγ antagonist (BADGE). These findings suggest that the insulin‐sensitizing effect of AM is mediated by formononetin through activation of PPARγ and insulin‐mediated signaling pathway, resulting in increased insulin sensitivity.
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