ANTIHYPERGLYCEMIC POTENTIAL OF BITTER MELON THROUGH ENZYME INHIBITION AND MOLECULAR PATHWAY ACTIVATION

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels due to impaired insulin secretion, insulin resistance, or both. The increasing global prevalence of DM has driven the search for natural-based therapies with fewer side effects. Bitter melon ( Momordica charantia L.), traditionally used for diabetes management, contains a diverse array of bioactive compounds with proven antihyperglycemic potential. This review assesses the antihyperglycemic activity of M. charantia, based on both in vitro and in vivo studies, with a focus on mechanisms involving enzyme inhibition and the activation of glucose metabolism signaling pathways. A systematic review of 17 research articles published between 2015 and 2025 revealed that M. charantia exerts strong antihyperglycemic effects through multiple mechanisms. In vitro findings showed significant inhibition of α-amylase and α-glucosidase enzymes, comparable to acarbose, mediated by polyphenols, flavonoids, saponins, and cucurbitane-type triterpenoids, which also protect pancreatic β-cells from oxidative stress. In vivo studies have demonstrated that extracts from the fruit, seeds, and leaves effectively reduce blood glucose levels, enhance insulin sensitivity, restore β-cell function, and improve lipid profiles in diabetic animal models. Key bioactive compounds such as charantin, polypeptide-P, cucurbitacin, lectin, and mcIRBP-9 peptide act synergistically by activating the IRS-1/PI3K/Akt signaling pathway, promoting GLUT4 translocation, and reducing oxidative damage. Overall, these findings indicate that M. charantia L. exhibits potent, multi-targeted antihyperglycemic activity through enzymatic and molecular pathways, supporting its potential as a safe and effective natural therapeutic agent for the management and prevention of diabetes mellitus and its complications