Molecular Docking and In Silico Predictive Analysis of Potential Herb-Drug Interactions Between Momordica charantia and Miglitol

Background Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a chronic metabolic disorder characterized by persistent hyperglycemia. Alpha-glucosidase inhibitors like miglitol delay carbohydrate absorption, thereby reducing postprandial glucose levels. <i>Momordica charantia</i> (bitter melon) has demonstrated hypoglycemic effects in various studies, yet its interactions with pharmaceutical antidiabetic agents remain poorly understood. This study investigates the molecular interactions between <i>M. charantia</i> phytoconstituents and miglitol's enzymatic targets using in silico methods. Methods An in silico approach was employed to assess potential herb-drug interactions between <i>M. charantia</i> and miglitol. Phytochemical screening identified 18 bioactive compounds from <i>M. charantia</i> that complied with Lipinski's Rule of Five, evaluated using SwissADME. Molecular docking was performed using AutoDock Tools (v1.5.7) to examine binding affinities between these phytoconstituents and key carbohydrate-metabolizing enzymes: lysosomal alpha-glucosidase (GAA), neutral alpha-glucosidases AB (GANAB) and C (GANC), maltase-glucoamylase (MGAM), and pancreatic alpha-amylase (AMY2A). The binding interactions were visualized using PyMOL and LigPlot+ to assess molecular stability. Results Molecular docking analysis revealed that charantin exhibited the highest binding affinity across all enzymes, particularly with neutral alpha-glucosidase AB (-12.4 kcal/mol) and maltase-glucoamylase (-12.6 kcal/mol), suggesting strong inhibitory potential. Other phytoconstituents, such as quercetin, luteolin, and kaempferol, also displayed moderate to high affinity, indicating possible synergistic effects. In contrast, compounds like cis-sabinol, myrtenol, and beta-sitosterol showed significantly weaker interactions. The binding interaction analysis confirmed stable hydrogen bonding and hydrophobic interactions between charantin and key enzymatic residues, reinforcing its role as a potent inhibitor of carbohydrate metabolism. Conclusion The study suggests that <i>M. charantia</i> phytoconstituents, particularly charantin, may enhance miglitol's effects by inhibiting the same carbohydrate-digesting enzymes. This could lead to increased glucose-lowering efficacy but also raises concerns about excessive inhibition, potentially resulting in postprandial hypoglycemia. These findings underscore the need for careful patient monitoring and dosage adjustments when combining <i>M. charantia</i> with alpha-glucosidase inhibitors. While molecular docking provides valuable insights, further in vitro and in vivo studies are essential to validate these computational predictions, assess bioavailability, and determine the clinical implications of <i>M. charantia-</i>miglitol co-administration.