Assessing Stigmasterol's Antidiabetic Potential Through Molecular Docking and DFT Approach

Introduction: Diabetes mellitus (DM) is a multimodal metabolic disease whose world inci-dence is estimated to reach approximately 366 million by the year 2030, even with the progress being made in biomedical research. The interaction of genetics, lifestyle, and environment complicates its management. Dipeptidyl peptidase IV (DPP-IV) and α-glucosidase inhibition a promising therapies: DPP-IV inhibition increases the effect of incretin and the release of insulin, and α-glucosidase inhibition postpones carbohydrate digestion and glucose absorption. Methods: Molecular docking and density functional theory (DFT) were employed to explore the anti-diabetic effect of stigmasterol, a phytosterol with Glycine max. Docking experiments were conducted to determine the binding affinities and interaction patterns between stigmasterol and DPP-IV and α-glucosidase. DFT analysis was done to obtain global reactivity descriptors and energy band gap, which estimated the electronic stability and reactivity of the molecule. Results: Stigmasterol exhibited high affinity towards the two target enzymes with docking scores of -8.8 kcal/mol to DPP-IV and -8.4 kcal/mol to α-galactosidase. The analysis of the DFT showed that it had a good (moderate) band gap and unaltered electronic configuration, which is indicative of good chemical reactivity and stability. Discussion: The binding affinities and electronic properties indicate that stigmasterol can be a dual DPP-IV and α-glucosidase inhibitor, which can be used synergistically to produce synergistic glycemic control via the regulation of incretin-mediated insulin release and postprandial carbohydrate absorption. The computational findings are in favor of its candidacy as a natural antidiabetic compound, but the weaknesses of in silico studies demand experimental confirmation. Conclusion: Stigmasterol has been suggested as a promising dual DPP-IV and alpha-glucosidase inhib-itor that could be useful in the management of diabetes mellitus. It needs to be further tested in vitro and in vivo to verify its biological efficacy, pharmacokinetics, and safety profile.