Synergistic Multi-Enzyme Inhibition by Sri Lankan Medicinal Plants: A Promising Strategy for Effective Diabetes Management - A Comprehensive Review

Diabetes mellitus (DM) remains a major global health burden, characterized by chronic hyperglycemia that leads to severe complications such as cardiovascular diseases, nephropathy, and neuropathy, significantly contributing to its high mortality rates. Effective management of post-prandial hyperglycemia is a key therapeutic strategy, with enzyme inhibition emerging as a promising approach. While targeting individual enzymes like alpha-amylase and alpha-glucosidase—responsible for starch breakdown—has shown efficacy, growing evidence suggests that the simultaneous inhibition of multiple key enzymes, including dipeptidyl peptidase-IV (DPP-IV), offers superior glucose regulation by preserving incretin hormones like Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Peptide (GIP). Medicinal plants, rich in bioactive compounds, have demonstrated the ability to exert multi-targeted inhibitory effects on these enzymes, exhibiting potent synergistic activity that enhances their therapeutic potential. This comprehensive review explores the pivotal roles of alpha-amylase, alpha-glucosidase, and DPP-IV in glucose metabolism and highlights medicinal plants with multi-enzyme inhibitory properties. By emphasizing the significance of synergistic inhibition, this review provides insights into the development of next-generation plant-based anti-diabetic therapeutics, offering a more effective, natural, and safer approach to managing DM.