Identification and Screening of Novel Antioxidant Peptides from Yak Skin and Their Protective Effect on H2O2-Induced HepG2 Cells Oxidation

To improve the bioavailability of yak by-products, novel antioxidant peptides were prepared and identified from yak skin hydrolysate. The results showed that the ultrafiltration fraction of a molecular weight of less than 1 kDa had the strongest free radical scavenging activity. A total of 219 novel peptides were identified by mass spectrometry and five antioxidant peptides were screened based on molecular docking with Keap1 (LMGPR, GFDGD, FGFDGDF, GHNGLDGL, and GPAGPQGPR). These peptides may bind with Keap1 competitively and exert antioxidant effects by activating the Nrf2/ARE pathway. After synthesis, FGFDGDF showed a better free radical scavenging ability and protective effect on H₂O₂-induced oxidative damage of HepG2 cells among these peptides. The pretreatment of peptides could enhance the activity of intracellular antioxidant enzymes and reduce the level of malondialdehyde and IL-8. This study provides a scientific basis for the application of yak skin peptide as a novel antioxidant in functional food.