The PPAR family of transcription factors are ligand-activated and regulate diverse functions including metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction in the body. Specifically, PPARα is known to play a role in reducing the levels of circulating triglycerides and regulating energy homeostasis in livestock animals. This study aimed to identify phytochemicals that could serve as ligands for modulation of the bovine nuclear peroxisome proliferator-activated receptor alpha (PPARα) using molecular docking studies. Therefore, we investigated 1000 flavonoids belonging to different groups for their ability to bind to PPARα using molecular docking. Out of 1000, 6 top lead compounds with maximum binding affinity, evaluated through molecular docking, were further analysed for physicochemical properties and drug-likeness attributes. The results revealed that two flavonoids, Quercetin-3-o-rhamnoside and (-)- epicatechingallate, which are known fatty acid synthase inhibitors, demonstrated high docking scores with PPARα (-8.66 kcal/mol and -8.49 kcal/mol, respectively) and low RMSD values with PPARα (1.61 kcal/mol and 1.28 kcal/mol, respectively) as compared to PPARα agonist (synthetic), fenofibrate (-6.24 kcal/mol and 2.19 kcal/mol) and thus analyzed further for prediction of stability of docked complexes through MD simulations. MD simulation studies predicted the stability of complexes and the complex of Quercetin-3-o-rhamnoside and (-)- epicatechingallate were found to be stable at 100 ns based on RSMD value and RMSF residue index. Through computational analysis, the screened compounds showed good pharmacokinetic parameters, including non-toxicity, non-carcinogenic, high gastrointestinal absorption and thus can serve as potential drug candidates. Finally, the findings suggest that these phytochemicals have the potential to act as potent PPARα pharmacological agonists to prevent disease mechanisms and their related complications, providing insights into the role of phytochemicals as feed additives in animals for modulating PPARα functions.Communicated by Ramaswamy H. Sarma.
Keywords: (-)- epicatechingallate; PPARα; Phytochemicals; quercetin-3-o-rhamnoside.