Synergistic Antioxidant and Antidiabetic Effects of Caesalpinia bonduc (L.) and Gymnema sylvestre (Retz.) in Alloxan-Induced Diabetic Rats.

Caesalpinia bonduc (L.) and Gymnema sylvestre (Retz.) are traditional remedies for diabetes management. This study explored their potential synergistic effects in alloxan (ALX)-induced diabetic Wistar rats. Aqueous-methanol extracts of C. bonduc seed kernels (C. bonduc extract [CBE]) and G. sylvestre leaves (G. sylvestre extract [GSE]) were phytochemically characterized. In vivo, experimental diabetic rats were treated with metformin (MET; 150 mg/kg), CBE (400 mg/kg), GSE (400 mg/kg), and a combined dose of CBE + GSE at 400 mg/kg (200 mg/kg of each plant extract) for 28 days. Biochemical analyses revealed significant antioxidant and hypoglycemic effects of the extracts, with the combined treatment (CBE + GSE) demonstrating superior outcomes. This combination improved fasting blood glucose, insulin, glycated hemoglobin A1c (HbA1c), and oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activities. Additionally, CBE + GSE significantly modulated insulin secretion and stress-related gene expression while downregulating the c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway. Histopathological results further confirmed the enhanced antidiabetic effects of the combination therapy. These findings suggest that the combined use of C. bonduc and G. sylvestre offers a promising therapeutic approach for diabetes management due to the complementary pharmacological activities of their phytochemicals.