MECHANISTIC INSIGHTS INTO THE SYNERGISTIC ANTIDIABETIC ACTIVITY OF OCIMUM SANCTUM AND METFORMIN THROUGH OXIDATIVE STRESS AND INSULIN SIGNALING PATHWAYS

Abstract

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia, insulin resistance, oxidative stress, and progressive pancreatic β-cell dysfunction. Metformin is the first-line oral antidiabetic drug widely used for the management of type 2 diabetes; however, long-term therapy is often associated with gastrointestinal intolerance and incomplete glycemic control in many patients. Ocimum sanctum (Tulsi), a traditional medicinal herb, is known for its potent antioxidant, antidiabetic, and cytoprotective properties. The present study investigates the mechanistic basis of the synergistic antidiabetic activity of Ocimum sanctum extract combined with metformin, with special emphasis on oxidative stress modulation and insulin signaling pathways. Experimental diabetes was induced in laboratory animals using streptozotocin, and treatment was carried out using Ocimum sanctum, metformin, and their combination. Key biochemical parameters including fasting blood glucose, serum insulin, HbA1c, lipid profile, and oxidative stress markers such as malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were evaluated. Additionally, the expression of insulin signaling pathway mediators including IRS-1, PI3K, Akt, and GLUT4 was analyzed to elucidate the molecular mechanism of synergy. The results demonstrated that the combination therapy produced significantly enhanced glycemic control compared to monotherapies. The synergistic effect was mediated through marked reduction in oxidative stress, restoration of antioxidant enzymes, and upregulation of insulin signaling proteins, resulting in improved glucose uptake and insulin sensitivity. These findings suggest that Ocimum sanctum potentiates the pharmacological efficacy of metformin by targeting both oxidative and insulin resistance pathways. The study highlights the therapeutic potential of herbal–allopathic combination strategies for effective and safer diabetes management.