Identification and molecular mechanism of novel antioxidant peptides from fermented pork trimmings: Integrated peptidomics, molecular docking/dynamics, and cell experiments

Pork trimmings, a major and underutilized by-product of pork processing, possess considerable potential for further exploitation. In this study, antioxidant peptides were isolated and identified from fermented pork trimmings, and their protective mechanisms against ethanol-induced oxidative damage in HepG2 cells were investigated. Utilizing a strategy integrating peptidomic analysis with molecular dynamics simulations, four novel peptides—VGWGR, LPPPR, LGPRYR, and WGGR—were identified, and their specific molecular interactions with Keap1 were elucidated. Among these, VGWGR exhibited the strongest binding affinity to Keap1, outstanding free radical scavenging capacity in vitro , and significant cytoprotective effects. Mechanistic studies further revealed that VGWGR activates the Keap1/Nrf2 pathway, leading to substantial upregulation of downstream antioxidant proteins (HO-1 and NQO1) and increased activities of endogenous antioxidant enzymes. This study not only enhances the value-added utilization of pork trimmings but also supports the potential of VGWGR as a functional food ingredient.