Nutraceutical potential of palm oil: Molecular targets and bioinformatics evaluation of constituents against type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized primarily by abnormally regulated glucose, lipid, and protein metabolism due to decreased insulin production and/or insulin resistance. The aim of this study was to evaluate the nutraceutical potential of palm oil constituents on human T2DM targets. In silico pharmacokinetic prediction, target prediction, molecular docking, toxicokinetic prediction, molecular dynamics, and target gene network analysis were employed. Compared to other compounds screened and selected, γ-linolenic acid displayed the lowest binding affinity with peroxisome proliferator-activated receptor alpha (PPAR-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), fatty acid-binding protein 2 (FABP2), and free fatty acid receptor 1 (FFAR1), while also demonstrating better binding affinity and potential inhibition than some clinically approved inhibitors targeting these receptors. Molecular dynamics simulation illustrated the stability of γ-linolenic acid in complex with the receptors. Androgen receptor, structural maintenance of chromosomes 3, and RAD21 cohesin complex component were the most enriched transcription factors, whereas casein kinase 2 alpha, mitogen-activated protein kinase 1 and extracellular signal-regulated kinase 1/2 were the most enriched expressed kinases that regulate the expression of the target genes. Glycogen synthase kinase-3-β, alpha serine/threonine kinase 1 and epidermal growth factor receptor, were some intermediate proteins predicted to interact with the transcription factors, kinases, and each other to drive T2DM pathogenesis. Overall, these findings suggest the binding of these molecular targets by palm oil constituents, particularly γ-linolenic acid, may modulate T2DM pathogenesis through multitarget capability, favourable pharmacokinetics and strong, stable binding affinities, supporting the nutraceutical potential of palm oil.