In silico computational screening and molecular dynamics analysis unveil Moringa oleifera phytochemicals as a promising PPAR-γ receptor agonist for targeted diabetes management strategies

Abstract The principal aim of this study was to detect potential pharmacologically active compounds in Moringa oleifera , which have shown promise as therapeutic agents against diabetes mellitus. Phytochemical structures obtained from verified PubChem database, andfurther analysed through molecular docking, ADMET prediction, modelling, and MMPBSA free energy calculations, with the peroxisome proliferator-activated receptor gamma (PPAR-γ) receptor protein target derived from the Protein Data Bank (PDB). This study screened 42 phytochemical compounds from M. oleifera for their binding affinity towards the catalytic site of the PPAR-γ protein. In a screening study, two specific molecules, epicatechin and genistein, exhibited remarkable binding affinity towards the catalytic site of the PPAR-γ protein. The bonding interfaces were noted to be superior to rosiglitazone,an economically available PPAR-γ agonist. Results from a comprehensive investigation showed that the bound ligands recognised collaborations with conserved protein zones through hydrogen bonding, polar contacts, and hydrophobic interactions. Specifically, molecular dynamics simulations and MM-PBSA free energy results (−22.28 ± 1.12 and −20.77 ± 0.55 kcal/mol, respectively) indicate that epicatechin and genistein exhibit good interactions with the PPAR-γ receptor. The phytochemicals identified in this researchdemonstrate their potential to effectively target this therapeutic target and establish a complex hydrogen bond network within the binding pocket. Particularly, the hydrogen binding route detected in the epicatechin and genisteinagentswas found to be more favourable and extensive when compared to the PPAR-γ agonists. This analytical approach specificallyaimed to recognise the best-performing phytochemicals from M. oleifera . This is to advance recent formulation of anti-diabetic medication, primarily for type 2 diabetes mellitus (T2DM) treatment. The results obtained revealed that the natural additives, epicatechin and genistein, can modulate PPAR-γ activitywith improved efficacy. These natural materials are more prospective and attractive for further explorationas potential therapeutic agents targeting this receptor.