Identification and characterization of anti-NAFLD peptides from fish maw using in silico analysis, molecular docking, and DFT quantum calculation.

Natural products are increasingly explored as potential remedies for non-alcoholic fatty liver disease (NAFLD). In this study, large yellow croaker fish maw (FM) peptides with potential anti-NAFLD were isolated using flavourzyme hydrolysis and LC-MS/MS sequencing. Three anti-NAFLD peptides, GPTGPPGPR (P6), GPPGPSGPS (P10), and GPSGPGGER (P12), were identified that exhibited strong binding to PPAR-γ, LXR-α, and LXR-β receptors. MD revealed H-bonding to key residues-Cys285 on PPAR-γ, His435 on LXR-β, and Arg305 on LXR-α-and extensive π-bonds strengthening receptor binding. GPTGPPGPR and GPPGPSGPS effectively inhibited lipid accumulation in oleic acid-induced HepG2 cell model, reducing intracellular triglycerides and total cholesterol, comparable to pioglitazone, while maintaining high CAT, SOD, and GSH-Px activities. This suggests that the isolated FM peptides could suppress hepatic steatosis, inhibit fatty acid and cholesterol accumulation, and activate intracellular antioxidants for free-radical scavenging and inflammation suppression, essential for NAFLD management.