The Effect of Cherry Laurel, Rutin Flavonoid and α-Lipoic Acid on Streptozotocin and Nicotinamide Induced Type 2 Diabetic Rats Given Metformin

Type 2 diabetes, characterized by insulin resistance, is a growing global health concern. The combined use of pharmaceutical medications and natural products for diabetes has become more common in recent years, although it is still unresolved how they might interact. This study aims to investigate the interactive effects of metformin and natural antioxidants—cherry laurel, rutin flavonoids, and α-lipoic acid—on metabolic and histological outcomes in a type 2 diabetes model. Six rat groups were used, five of the groups rendered diabetic using nicotinamide (110 mg/kg) and streptozotocin (65 mg/kg, i.p.). For 12 weeks, animals received oral doses of metformin (500 mg/kg) and the combinations of metformin and natural products. Serum was analyzed for glucose, lipid profile, ceruloplasmin, plasma for nitric oxide and pancreatic tissue for histopathological changes and, insulin immunoreactivity. Ceruloplasmin levels were significantly higher in diabetic rats (22.89 ± 2.85 U/L) compared to the diabetic + metformin + rutin group (14.32 ± 0.73 U/L). Nitric oxide levels were lower in diabetic rats (61.27 ± 6.26 µmol/L) but elevated in the metformin-only group (110.22 ± 11.44 µmol/L). Histopathological evaluation showed pronounced pancreatic atrophy in the diabetic, diabetic + metformin + cherry laurel, and diabetic + metformin + rutin groups, while the diabetic + metformin group exhibited preserved tissue. Interestingly, insulin secretion was lower in the combination therapy groups (especially the use of rutin flavonoid and α-lipoic acid) compared with the control and diabetic + metformin group, suggesting potential antagonistic effects. Although glucose levels were not markedly different across treatment groups, histological findings revealed more pronounced tissue damage in antioxidant-metformin combinations than with metformin alone. These results highlight the importance of evaluating natural product–drug interactions before co-administration.