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

Authors Lv, Yibing; Zhao, Ping; Pang, Kejian; Ma, Yuanren; Huang, Huiqi; Zhou, Tongxi; Yang, Xinzhou

Journal JOURNAL OF ETHNOPHARMACOLOGY , MAR 25 2021,:268

DOI 10.1016/j.jep.2020.113654 PubMed 33271248

Abstract Headings ethnopharmacological relevance: Sophora 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 study: This 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 methods: The main six chemical constituents of SA-FRE were elucidated based on an off-line semipreparative 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.Results: In vivo, 4-week treatment of SA-FRE ameliorated hyperglycemia, dyslipidemia, and insulin resistance in diabetic mice. Mechanically, SA-FRE regulated PPAR alpha and PPAR gamma 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 mu g/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 God6983, a PKC inhibitor, reversed the SA-FRE-induced GLUT4 translocation and expression at the gene and protein levels.Conclusions: Generally, SA-FRE ameliorated hyperglycemia, dyslipidemia, and insulin resistance partly through activating PKC/GLUT4 pathway and regulating PPAR alpha and PPAR gamma expression.

Species covered 苦豆子 Sophora alopecuroides