Synergistic Effects of Metformin and Naringenin in Diabetes Management

Naringenin, a flavonoid found in citrus fruits, has demonstrated antidiabetic effects similar to metformin via stimulation of AMPK (adenosine monophosphate-activated protein kinase) pathways. This study investigated the combined effects of naringenin (NAR) and metformin (MET) on body weight regulation, glycemic control, lipid profiles, and various metabolic parameters in diabetic and non-diabetic rat models. Male wistar rats were divided into six groups: non-diabetic control, non-diabetic treated with metformin and naringenin, diabetic control (induced with nicotinamide and streptozotocin), and three diabetic groups treated with metformin (50 mg/kg) plus varying doses of naringenin (25, 50, and 100 mg/kg). The study duration was 35 days, with daily oral administration of treatments. Diabetic rats showed significant weight loss compared to normal controls, but treatment with different combinations showed weight recovery. Elevated fasting blood glucose (FBG) levels and reduced glycogen content were observed in diabetic rats, which were significantly improved by all tested combinations of MET and NAR. Cholesterol and triglyceride levels decreased significantly in diabetic rats treated with all MET+NAR combinations, while HDL-cholesterol increased across all treatments. Inflammatory markers were elevated in diabetic rats but showed dose-dependent reductions with MET + NAR treatments, alongside improvements in antioxidant enzymes and glucokinase (GCK) levels. Histological analysis revealed that (MET 50 +NAR 25) provided the most effective restoration of pancreatic and liver architecture, minimizing damage compared to other treatment groups. The combination of metformin and naringenin demonstrates significant potential in managing diabetes through synergistic effects on glycemic control, lipid metabolism, oxidative stress, and inflammation.