Computational investigation of lignans as potential target for non-alcoholic fatty liver disease: Insights from network pharmacology, docking, DFT, and dynamics simulation analysis

NAFLD is a major cause of morbidity and mortality worldwide. The present study aims to investigate the therapeutic potential of selected lignans, including 6-hydroxy enterodiol and secoisolariciresinol, against the key molecular targets involved in the pathogenesis of the disease. A network pharmacology approach was employed to elucidate the interaction between the proteins of bioactive compounds and disease targets, while docking and density functional theory (DFT) calculations were conducted to assess the electronic properties and reactivity profiles of the ligands. GO and KEGG pathway enrichment analysis was done to understand the core targets that are involved in various biological pathways and biological functions. Furthermore, dynamic validation of the stability and conformational behavior of the protein-ligand complexes under the physiological condition was done through MM-GBSA free energy calculations, Free Energy Landscape (FEL) mapping, and Principal Component Analysis (PCA). AKT1, CASP3, and IL6 exhibited highly favorable binding free energies, which range from 75.0196 to 75.2026 kcal/mol, indicating the stability and binding of the proteins. Moreover, CASP3 exhibited a low energy gap and a high electrophilicity index, underscoring its potential as an effective electron acceptor. In conclusion, the present computational study provides substantial evidence for the efficacy of a group of peptides as natural therapies for the treatment of nonalcoholic fatty liver disease.