Simulated gastrointestinal digestion of walnut protein yields anti-inflammatory peptides

The impact of the simulated gastrointestinal digestion process on walnut protein and the potential anti-inflammatory properties of its metabolites was studied. Structural changes induced by digestion, notably in α-Helix, β-Turn, and Random Coil configurations, were unveiled. Proteins over 10,000?Da significantly decreased by 35.6?%. Antioxidant activity in these metabolites paralleled increased amino acid content. Molecular docking identified three walnut polypeptides—IPAGTPVYLINR, FQGQLPR, and VVYVLR—with potent anti-inflammatory properties. RMSD and RMSF analysis demonstrated the stable and flexible interaction of these polypeptides with their target proteins. In lipopolysaccharide (LPS)-induced inflammation in normal human colon mucosal epithelial NCM460 cells, these peptides decreased 5-hydroxytryptamine (5-HT), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) expression, while mitigating cell apoptosis and inflammation. Our study offers valuable insights into walnut protein physiology, shedding light on its potential health benefits.