Sanbai Melon Seed Oil Exerts Its Protective Effects in a Diabetes Mellitus Model via the Akt/GSK-3β/Nrf2 Pathway

Traditional Chinese medicine (TCM) plays an important role in the treatment of type 2 diabetes mellitus (T2DM). However, the lack of adequate and scientifically rigorous evidence has limited its application in this disorder. Sanbai melon seed oil (SMSO) is used in folk medicine to treat DM; however, only few literature reports exist regarding its mechanism. Herein, we aimed to confirm the antidiabetic activity of SMSO in a T2DM model and further elucidate its possible mechanisms. The T2DM rat model was induced by high-fat and sugar diet and streptozocin (STZ, 40 mg/kg). SMSO was administered at doses of 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg. Several biochemical parameters and antioxidant protein levels were measured to evaluate the hyperglycemic and antioxidant activities of SMSO. Western blotting was performed to determine its potential mechanism. Based on the results, SMSO treatment significantly reduced blood glucose levels, increased plasma insulin, and repaired islet tissue injury in diabetic rats (P < 0.05). To add, it markedly reduced MDA levels and increased that of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Western blot results showed that SMSO induced n-Nrf2 and HO-1 expression and Akt and GSK-3β phosphorylation in a dose-dependent manner. Further studies showed that LY294002, aPI3K inhibitor, abolished the effects of SMSO on GSK-3β phosphorylation and Nrf2 nuclear translocation as well as the protective effects on pancreatic β cells. Together, these results suggest that SMSO regulates the Akt/GSK-3β/Nrf2 pathway and induces the expression of antioxidant proteins to impede oxidative stress in rats with T2DM.