Structure–activity relationship and antioxidant properties of walnut peptides with high intestinal absorption capacity

Walnut peptides are a good source of natural antioxidants; however, intestinal digestion and absorption might limit this antioxidant activity. In this research, 5 antioxidant peptides were identified among 33 walnut peptides, exhibiting good intestinal absorption. Quantum chemical methods were used to analyze the electronic structure characteristics of the five peptides. In addition, molecular docking was used to preliminarily predict the interaction patterns between the peptides and potential targets. In vitro assays and an oxidative stress model in PC12 cells were used to evaluate the antioxidant properties of the peptides. Among the five walnut peptides, WSPSGR exhibited the lowest E_LUMO, Δ_EL-H, and binding energy values (-9.9 kcal mol^-1), along with excellent radical scavenging capacity (ABTS clearance rate reached 94.83 ± 1.39%). It significantly enhanced cellular antioxidant defense, increasing the survival rate of scopolamine-treated cells from 52.89 ± 1.36% to 70.84 ± 1.45%. Additionally, WSPSGR improved mitochondrial function while decreasing oxidative stress. WSPSGR can activate the MLCK signaling pathway and improve paracrine transport efficiency, providing a theoretical basis for the development of bioavailable walnut peptide-based antioxidant food ingredients.