Inhibitory effects and action mechanism of five antioxidant peptides derived from wheat gluten on cells oxidative stress injury

Our previous study identified five peptides Leu-Tyr (LY), Pro-Tyr (PY), Tyr-Gln (YQ), Ala-Pro-Ser-Tyr (APSY), and Arg-Gly-Gly-Tyr (RGGY) from wheat gluten. However, the mechanism of antioxidant action and structure-function relationship of these five peptides were still unclear. In this study, we found that five peptides induced by AAPH in human embryonic kidney cells (HEK-293) suppressed the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, they also upregulated the antioxidant activity-related enzymes (SOD, CAT and GSH-Px) and GSH activities. Additionally, five peptides treatment decreased Keap1 protein level and increased Nrf2 and HO-1proteins levels. It was concluded that five peptides showed promise in activating the Keap1-Nrf2-HO-1 signaling pathway and enhancing the antioxidant defense system. Quantum chemical calculation and molecular docking technologies were used to explore the action mechanism of five wheat peptides. Five antioxidant peptides were able to effectively bind Keap1, and the peptides predominantly formed hydrogen and π bonds during their binding with the active pocket region of Keap1.