Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model

BACKGROUND: The increased prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients is becoming a worldwide health burden. Studies have indicated, however, that the onset of NAFLD occurs during pre-diabetes, a condition that often precedes the onset of T2DM. Oleanolic acid has been reported to improve glucose homeostasis in diet-induced pre-diabetes; however, the effects of this triterpene on liver function have not been evaluated. PURPOSE: This study was aimed at evaluating the therapeutic effects of oleanolic acid (OA) on selected markers of NAFLD in a pre-diabetes rat model. METHODS AND MATERIALS: Pre-diabetes was induced by exposing Sprague Dawley rats to a high-fat high-carbohydrate diet for 20 weeks. The pre-diabetic rats were then treated with OA (80 mg/kg) or metformin (500 mg/kg) in the presence and absence of dietary interventions for a period of 12 weeks. The effects of OA were evaluated on parameters including plasma triglycerides (TGs), very low-density lipoprotein (VLDL) particles, bilirubin, AST, ALT, SREBP and antioxidant profile while the livers were collected for histological analysis. RESULTS: The findings of this study showed that the administration of OA to pre-diabetic rats ameliorated body/liver weights ratio and significantly decreased plasma triglycerides (TGs) and VLDL. Furthermore, OA also ameliorated hepatic oxidative stress, lowered the SREBP expression and intrahepatic TGs. In addition, OA administration decreased plasma concentrations of bilirubin and liver damage enzyme biomarkers. CONCLUSION: The findings of the study suggest that OA ameliorates the risk of developing pre-diabetes-related NAFLD through the prevention of intrahepatic fat accumulation while also lowering hepatic inflammation.