Screening and mechanistic study of antioxidant peptides from Bangia fusco-purpurea targeting the Keap1–Nrf2 pathway

Using 2236 peptides derived from Bangia fusco-purpurea as ligands and the Kelch domain of Kelch-like ECH-associated protein 1 as the receptor, molecular docking was employed to screen peptides with strong inhibitory effects on Kelch-like ECH-associated protein 1–nuclear erythroid 2-related factor interactions. Subsequently, an H2O2-induced oxidative damage model was established using human umbilical vein endothelial cells to validate the results. The most active antioxidant peptides, IAY and TIL, induced nuclear erythroid 2-related factor translocation from the cytoplasm to the nuclei of human umbilical vein endothelial cells when subjected to oxidative damage. Nuclear erythroid 2-related factor activation resulted in the upregulation of the downstream target proteins, including nicotinamide adenine dinucleotide phosphate, quinone oxidoreductase 1, heme oxygenase-1, glutathione, and superoxide dismutase. This cascade reduced the malondialdehyde and reactive oxygen species levels, thereby alleviating oxidative stress, and inhibited H2O2-induced cell apoptosis by regulating apoptosis-related proteins. This study successfully identified IAY and TIL as antioxidant peptides that capable of interfering with Kelch-like ECH-associated protein 1–nuclear erythroid 2-related factor interactions, and elucidated the underlying cellular and molecular mechanisms, laying the groundwork for further research and application of antioxidant peptides.