Screening of phytochemicals from Withania somnifera, Rauwolfia serpentina, Curcuma longa, and Camellia sinensis for potential maltase-glucoamylase (MGAM) inhibition using molecular docking, molecular dynamics simulation, and ADMET analysis

Postprandial hyperglycemia is a major concern in type 2 diabetes, and inhibition of intestinal α-glucosidases [maltase-glucoamylase (MGAM)] is an established approach for controlling postprandial glucose excursions. In this study, an in silico screening of phytochemicals from different medicinal plants, including Withania somnifera, Rauwolfia serpentina, Curcuma longa, and Camellia sinensis, was conducted against MGAM using the clinically approved inhibitor miglitol as a reference for protocol validation. Molecular docking predicted that miglitol binds to MGAM (PDB ID: 3L4W) with a binding energy of -6.86 kcal/mol; however, several phytochemicals exhibited comparatively stronger predicted binding affinities. Among these, Withanolide B (-9.25 kcal/mol), yohimbine (-8.50 kcal/mol), raubasine (-8.46 kcal/mol), and Withanone (-7.57 kcal/mol) demonstrated higher predicted binding affinities than the other screened compounds. Furthermore, molecular dynamics simulation of the MGAM-Withanolide B complex suggested stable hydrophobic interactions between Withanolide B and key catalytic residues of MGAM, together with a favorable predicted MM-GBSA free energy (-17.33 kcal/mol). In silico ADME profiling further predicted favorable gastrointestinal absorption for the lead phytochemicals, supporting their potential for oral intestinal activity. Collectively, these findings suggest that plant-derived phytochemicals, particularly Withanolide B from Withania somnifera, may serve as promising candidates for further experimental validation in enzyme inhibition assays and glucose tolerance models. The results also indicate that enrichment of Withanolide B may improve the therapeutic potential of Withania somnifera extracts.