Antidiabetic effect of a flavonoid-rich extract from Sophora alopecuroides L. in HFD- and STZ- induced diabetic mice through PKC/GLUT4 pathway and regulating PPARα and PPARγ expression

Abstract

Headings ethnopharmacological relevanceSophora alopecuroides L. is a traditional ethnopharmacological plant, which is widely used in traditional Chinese medicine and Mongolian and Uighur medicine to ameliorate “thirst disease”. Aim of the studyThis study aimed to investigate the antidiabetic activities and mechanisms of a flavonoid-rich extract from Sophora alopecuroides L. (SA-FRE) both in vivo and vitro. Materials and methodsThe main six chemical constituents of SA-FRE were elucidated based on an off-line semi-preparative liquid chromatography nuclear magnetic resonance (LC-NMR) protocol. Myc-GLUT4-mOrange-L6 cell models and mouse model with diabetes induced by high-fat diet combined with STZ injection were respectively adopted to investigate the antidiabetic effects of SA-FRE both in vitro and vivo. ResultsIn vivo, 4-week treatment of SA-FRE ameliorated hyperglycemia, dyslipidemia, and insulin resistance in diabetic mice. Mechanically, SA-FRE regulated PPARα and PPARγ expression in white adipose tissue (WAT) and liver, thereby ameliorating dyslipidemia. Moreover, SA-FRE increased the phosphorylation of PKC and further stimulated the GLUT4 expression in WAT and skeletal muscle, thus increasing the glucose utilization in vivo. In vitro, 50 μg/mL SA-FRE increased GLUT4 translocation to about 1.91-fold and glucose uptake to 1.82-fold in L6-myotubes. SA-FRE treatment increased the GLUT4 expression at both gene and protein levels. Furthermore, only Gö6983, a PKC inhibitor, reversed the SA-FRE-induced GLUT4 translocation and expression at the gene and protein levels. ConclusionsGenerally, SA-FRE ameliorated hyperglycemia, dyslipidemia, and insulin resistance partly through activating PKC/GLUT4 pathway and regulating PPARα and PPARγ expression.