Structure–Activity Relationship and Antioxidant Properties of Walnut Peptides with High Intestinal Absorption Capacity

Abstract

Walnut peptides are a good source of natural antioxidants, but intestinal digestion and absorption may limit this activity. In this work, 5 antioxidant peptides were identified from among 33 walnut peptides, which exhibited good intestinal absorption. The basis of the antioxidant activity of the five peptides was analyzed using quantum chemical methods, and the structure–activity relationships of the peptides with cellular targets were investigated using molecular docking software. The antioxidant properties of the peptides were evaluated through in vitro assays and an oxidative stress model in PC12 cells. Among the five walnut peptides, WSPSGR exhibited the lowest ELUMO, ΔEL–H, and binding energy values (–9.9 kcal/mol), along with excellent radical scavenging capacity (the clearance rate of ABTS reached 94.83±1.39%). It significantly enhanced cellular antioxidant defenses, increasing the survival rate of scopolamine–treated cells from 52.89±1.36% to 70.84±1.45%. In addition, WSPSGR improved mitochondrial function while reducing oxidative stress and promoting membrane fluidity and permeability in Caco–2 cells. This study provides the basis for developing bioavailable walnut peptides as antioxidant ingredients in foods.