Astragaloside IV ameliorates insulin induced insulin resistance in HepG2 cells through reactive oxygen species mediated c-Jun N-terminal kinase pathway.

Abstract

To investigate the effects and elucidate the mechanism of Astragaloside IV (AS-IV) for insulin resistance (IR) and type 2 diabet es mellitus (T2DM). CCK8 kit was used to detect cell viability, glucose detection kit was used to detect the concentration of glucose in cell supernatant, reactive oxygen species (ROS) detection kit and Western blot were used to explore the mechanism of Astragaloside IV (AS-IV) in improving IR. A diabetic rat model was also established by feeding high sugar and fat diet and streptozotocin (STZ) injection. After treatment with AS-IV, rosiglitazone (ROZ), or normal saline, the fasting blood glucose (FBG), C peptide (C-P), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and the glucose tolerance were assessed. AS-IV could effectively reduce the content of ROS and increase the glucose uptake in high insulin-treated IR-type HepG2 cells. The results of molecular mechanisms indicated that AS-IV could improve insulin resistance by reducing JNK phosphorylation and regulating c-Jun N-terminal kinase (JNK) downstream protein expression. Additionally, AS-IV could significantly reduce the levels of FBG, TNF-α, IL-6 and the glucose tolerance in diabetic rats ( < 0.05 or < 0.01). The high and medium dose groups of AS-IV could significantly increase the C-P levels in diabetic rats ( < 0.05 or < 0.01). Our results indicated that AS-IV improve liver IR through the JNK pathway and ROS, which meant a new molecular target for the treatment of diabetes. The AS-IV also helped to prevent and improved the insulin resistance of rats.