Novel Antioxidant Peptides Derived from Feather Keratin Alleviate H2O2-Induced Oxidative Damage in HepG2 Cells via Keap1/Nrf2 Pathway

Reactive Oxygen Species (ROS) are crucial for signal transduction and the maintenance of cellular homeostasis. However, superfluous ROS may engender chronic pathologies. Feather keratin is a promising new source of antioxidant Peptides that can eliminate excess ROS and potentially treat oxidative stress-related diseases, but the underlying mechanisms have remained elusive. This study investigated the antioxidant effects and mechanisms against H₂O₂-induced oxidative damage in HepG2 cells of the two latest discovered antioxidant Peptides, CRPCGPTP (CP-8) and ANSCNEPCVR (AR-10), first decrypted from feather keratin. The results revealed that CP-8 and AR-10 did not exhibit cytotoxicity to HepG2 cells while reducing intracellular ROS accumulation. Simultaneously, they enhanced the activities of catalase (CAT), superoxide dismutase (SOD), and Glutathione Peroxidase (GSH-Px), thus alleviating H₂O₂-induced cell Apoptosis. Molecular docking analysis demonstrated that CP-8, AR-10 interacted well with the key Amino acids in the Kelch domain of Keap1, thereby directly disrupting the Keap1-Nrf2 interaction. The peptides' biosafety and antioxidant activity via Keap1/Nrf2 signaling lay the groundwork for further animal studies and applications as functional food additives.

Keap1/Nrf2 pathway; antioxidant peptide; feather keratin; oxidative damage.