Elucidating the alpha-glucosidase inhibitory activity of Parinari curatellifolia: An in vitro and in silico study

Alpha-glucosidase catalyzes glycosidic bond hydrolysis to release glucose, and its inhibition slows intestinal glucose absorption, offering a therapeutic strategy for type 2 diabetes management. Given Parinari curatellifolia 's traditional hypoglycemic use and reported antidiabetic activity, this study evaluated its leaf extract and bioactive compounds as potential alpha-glucosidase inhibitors. An in vitro alpha-glucosidase inhibition assay was performed on the ethanol extract, followed by GC-MS analysis, molecular docking, induced fit docking (IFD), molecular dynamics simulations, and ADMET predictions. Results showed concentration-dependent enzyme inhibition. GC-MS analysis tentatively identified biologically active molecules including Cinnamic acid derivatives, Phenolics, Dihydroartemisinin, Phytol, Levoglucosan, and Stevioside. Docking analysis highlighted Compound NP-002173 and Stevioside with scores of −9.776 and −9.73 kcal/mol, comparable to Acarbose (−9.764 kcal/mol). IFD yielded higher docking scores: Compound NP-002173 (−10.412 to −9.488 kcal/mol; consensus −9.952 kcal/mol) and Stevioside (−11.183 to −9.308 kcal/mol; consensus −10.082 kcal/mol). Both compounds formed multiple hydrogen bonds with key residues (ASP 34, ASP 305, ARG 634, ASP 640, HIE 698, ASP 451, TRP 423) and π-π stacking interactions with TRP 423, TRP 525, and PHE 673. Molecular dynamics simulations confirmed Stevioside's stable binding, maintaining interactions with ASP 640 and ASP 564. Most compounds exhibited favorable ADMET profiles, although Compound NP-002173 and Stevioside may require optimization to improve bioavailability. These findings suggest Parinari curatellifolia and its constituents, particularly Stevioside and Compound NP-002173, as promising candidates for anti-diabetic drug development.