The Role of Naringenin in Enhancing Metformin Efficacy in Diabetic Rats

Background: Diabetes mellitus is linked to hepatic dysfunction, requiring effective therapeutic strategies. Metformin (MET), a standard antidiabetic agent, and naringenin (NAR), a citrus flavonoid, have shown complementary actions in enhancing insulin sensitivity and reducing oxidative damage through activation of AMP-activated protein kinase (AMPK). This study explores the dose-dependent effects of MET and NAR combinations on liver function and antioxidant status in diabetic rats. Methods: Sixty male wistar rats were divided randomly into six groups: G1, normal control; G2 vehicle control (MET 50 mg/kg + NAR 50 mg/kg); G3, diabetic group (injected ip with nicotinamide (230 mg/kg) followed by streptozotocin (65 mg/kg), and three diabetic treated groups G4, G5 and G6 received MET (50 mg/kg) with NAR at 25, 50, or 100 mg/kg. respectively. Treatments were administered orally for five weeks. Body weight and fasting blood glucose (FBG) were recorded weekly, along with biochemical liver function parameters and total antioxidant capacity at the end of the experiment. Results: Diabetic rats showed significant weight loss, elevated FBG, liver enzymes (ALT, AST), and bilirubin, alongside reduced total protein and total antioxidant capacity (TAC). Treatment with MET plus NAR significantly resulted in body weight increase, FBG, liver enzymes and TAC normalized compared to untreated diabetic rats. Conclusion: These findings suggest that the combination of metformin and naringenin exerts synergistic antidiabetic and hepatoprotective effects. At the same time improve the antioxidant status in diabetic rats.