Osteopontin-Derived Peptide YPDAVATWL Modulates NF-κB Signaling and Exhibits Anti-Inflammatory Activity in Mammary...

Osteopontin (OPN) and its digestion-derived peptides exhibit anti-inflammatory potential, yet the specific functional peptides and their cellular mechanisms remain incompletely understood. In this study, an OPN-derived peptide YPDAVATWL, was identified following simulated gastrointestinal digestion and characterized in terms of its stability and bioactivity. The peptide exhibited resistance to digestive protease hydrolysis and demonstrated antioxidant activity in vitro. Using goat mammary epithelial cells (GMECs) as an epithelial cell model, YPDAVATWL was found to modulate the expression of key inflammation-related factors and suppress NF-κB pathway activation, as indicated by reduced IKKβ and IκBα phosphorylation and decreased nuclear translocation of p65. Structure prediction analysis suggested that YPDAVATWL may associate with the scaffold dimerization domain of IKKβ, potentially affecting its activation process. Collectively, these results indicate that YPDAVATWL modulates inflammatory signaling in epithelial cells and provide mechanistic insights into the structure-function relationship of food-derived bioactive peptides at the cellular level.