In Silico Screening of Indian Medicinal Herb Compounds for Intestinal α-Glucosidase Inhibition with ADMET and Toxicity Assessment for Postprandial Glucose Management in Type-2 Diabetes

Abstract Postprandial hyperglycemia is a major concern in type 2 diabetes, and inhibition of intestinal α-glucosidases [maltase–glucoamylase (MGAM)] is an established method for controlling post-meal glucose excursions. In this study, we conducted an in-silico screening of phytochemicals from different well-known medicinal plants (Withania somnifera, Rauwolfia serpentina, Curcuma longa, and Camellia sinensis) against MGAM, using the clinically approved inhibitor miglitol as reference for docking protocol validation. Molecular docking revealed that miglitol binds to MGAM with a binding energy of −6.86kcal/mol and an RMSD of 1.04 (with co-crystal structure; PBD ID:3L4W); however, several phytochemicals exhibited binding affinities equal to or stronger than miglitol. Among these, Withanolide B (−9.25kcal/mol) and Withanone (−7.57kcal/mol) from Withania somnifera showed the highest predicted affinities, indicating robust engagement of the MGAM catalytic pocket. Rauwolfia serpentina alkaloids such as yohimbine (−8.50kcal/mol) and raubasine (−8.46kcal/mol) also displayed strong binding energies, whereas curcuminoids (curcumin −6.36kcal/mol; deoxycurcumin −6.35kcal/mol) and tea catechins (e.g., epicatechin gallate −6.85 kcal/mol) demonstrated moderate affinity. Interaction analysis showed that top-ranking compounds formed extensive hydrogen-bonding and hydrophobic interactions with key catalytic residues of MGAM, suggesting stable occupancy of the active site. In-silico ADME profiling predicted favorable gastrointestinal absorption for lead phytochemicals, supporting their potential for oral intestinal action. Collectively, these results identify plant-derived ligands with binding energies comparable to or exceeding that of miglitol, highlighting Withania somnifera withanolides as priority candidates for experimental validation in enzyme inhibition assays and glucose tolerance models, and providing a focused set of natural MGAM inhibitors for further translational investigation in postprandial glucose control. Competing Interest Statement The authors have declared no competing interest.