Caspase/AIF/apoptosis pathway: a new target of puerarin for diabetes mellitus therapy

Abstract Pancreatic β cell damage is one of the crucial factors responsible for the development of type 2 diabetes mellitus (T2DM). Previous studies have suggested that puerarin (PR) could regulate the activities of the mitochondrial respiratory chain complex in diabetic nephropathy (DN); however, whether PR can inhibit pancreatic β-cell apoptosis in T2DM remains to be elucidated. In the present study, T2DM mice induced by high-fat diet and streptozotocin (STZ) injection were used as a working model to investigate the mechanism of PR on pancreatic β cell apoptosis. The results showed that PR decreased the serum fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels but significantly increased the fasting blood insulin (FINS) and high-density lipoprotein (HDL) levels. Furthermore, decreased caspase-3, 8, 9 and apoptosis-inducing factor (AIF) proteins in the pancreas were detected by Western blot analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining demonstrated that the pancreatic β cell apoptosis was inhibited by PR. Furthermore, PR improved the histopathological changes in pancreatic tissue in T2DM mice. Collectively, the data show that PR can protect the β cells from apoptotic death in a mouse model of T2DM through regulating the expression of apoptosis-related protein-AIF and caspase family proteins.