Novel antioxidant peptides identified from wheat germ protein: Structure-activity relationships, stability, and...

Wheat germ protein, a potential natural source of antioxidant peptides, remains underutilized. This study aimed to identify and characterize novel antioxidant peptides from wheat germ protein after in vitro digestion. The results demonstrated that six peptides were identified through a systematic approach combining separation technology, peptidomics, in silico analysis and antioxidant evaluation. Their antioxidant capacity was governed by specific active sites (Trp, Tyr, Phe, His) and spatial conformations rich in β-sheet and β-turn structures. Notably, the peptides YFGWPGPK, FGWPGPR, and GHHWPLPP exhibited protective capabilities (∼78.83% at 200 μM) on H₂O₂ damaged PC12 cells by lowering reactive oxygen species (ROS) level, increasing antioxidant enzymes activity, and reducing malondialdehyde (MDA) content. Furthermore, FGWPGPR and GHHWPLPP bound to the Keap1 active site and activated Nrf2 expression, thereby modulating the Keap1-Nrf2 signaling pathway. This study broadens the utilization of wheat germ protein as a natural reservoir for the development of bioactive peptides.