Novel antioxidant peptides from chicken bone hydrolysate: Identification, structure–activity relationship and cytoprotective effects against oxidative stress in HaCaT cells

The objective of this study was to identify antioxidant peptides from chicken bone hydrolysate, elucidate their molecular mechanisms, and investigate their protective effects against oxidative damage in HaCaT cells. Four novel antioxidant peptides—SGQLSGPIRFF, LSGPIRFF, LIVYPW, and IFPVHWQF—were identified using nano-LC–MS/MS. Molecular docking results indicated that these peptides can interact with Keap1, indicating their potential involvement in the Keap1–Nrf2 signaling pathway. LIVYPW exhibits the highest E HOMO (−5.6576 eV) and the smallest HOMO–LUMO energy gap (5.0042 eV), showing superior electron-donating ability compared with the other three peptides. Further analysis suggested that the active site of LIVYPW was potentially located at the O47 position of Trp-6. Additionally, these peptides significantly reduce H₂O₂-induced oxidative damage by reducing intracellular reactive oxygen species levels and enhancing antioxidant enzyme activity (SOD, CAT, and GSH-Px). Our results provide a preliminary scientific basis for the potential valorization of chicken bone-derived peptides. • Four novel antioxidant peptides were identified from chicken bone hydrolysate. • Arg415 and Arg380 were the key binding sites of Keap1–peptides. • Quantum analysis revealed Trp6 as a key active site for LW-6. • LW-6 significantly reduced intracellular ROS levels and enhanced antioxidant enzyme activity.