An integrated investigation combining network pharmacology and computer simulation dissects the potential mechanism of anti-obesity of Monascus pigments (MPs)

Monascus pigments (MPs), the secondary metabolites of Monascus-fermented foods, have been widely studied for their anti-obesity effects. However, the specific targets and potential mechanism of MPs for anti-obesity remain unclear. In this study, we applied network pharmacology and computer simulation to investigate the anti-obesity potential and action mechanism of MPs. Based on public databases, 117 potential therapeutic obesity targets of MPs were predicted. Five key targets (STAT3, ESR1, BCL2, PPARG, and MMP9) were obtained by protein-protein interaction (PPI) analysis and microarray data validation. The enrichment results showed that MPs exerted anti-obesity effects through multiple targets and multiple pathways, especially insulin resistance. Molecular docking demonstrated the binding of five key targets to MPs ligands through hydrophobic interactions and hydrogen bonding. Molecular dynamics simulation and binding free energy analysis revealed a higher stability in the binding of ESR1, BCL2, and PPARG targets with MPs ligands. In addition, free energy landscape (FEL) and independent gradient model (IGM) analysis showed that van der Waals forces were also the main driving force in stabilizing the binding of key targets and MPs ligands. This study systematically illustrated the potential anti-obesity mechanism of MPs and established the foundation for the development and application of MPs as anti-obesity functional additives.