The transepithelial transport and membrane diffusion pathways of the walnut meal-derived antioxidant peptide YR-10 were investigated using Caco-2 monolayer cells and DPPC liposome models

The transport and absorption of antioxidant peptides are critical for their biological activity. The walnut meal-derived peptide YWSPNDEQFR (YR-10) has been shown to alleviate oxidative stress–induced liver injury, but its absorption mechanisms remain unclear. In this study, we employed a Caco-2 monolayer, DPPC liposomes, and molecular docking to characterize the transepithelial transport of YR-10 across the intestinal epithelium. YR-10 was absorbed through clathrin-mediated endocytosis and paracellular pathway, with significantly promotes the restoration of ZO-1 and closure protein gene expression, indicating its ability to restore the integrity of the epithelial barrier. Further research revealed that YR-10 binding to lipid bilayers was predominantly entropy-driven, involving electrostatic, hydrogen-bonding, and hydrophobic interactions that regulated membrane fluidity and order. These findings collectively elucidate the intestinal absorption mechanism of YR-10 and provide a theoretical basis for improving the bioavailability of walnut powder-derived bioactive peptides in functional food applications.