Identification and Functional Characterization of Cytoprotective Crocodile-Derived Peptides against Oxidatively...

Oxidative stress-induced cellular damage is a primary contributor to pathological conditions such as accelerated skin aging. Consequently, there is a strong demand for efficacious antioxidants. Herein, we investigate the cytoprotective properties of Crocodylus siamensis white blood cell extracts and peptides derived from them against H₂O₂-induced oxidative damage in HaCaT keratinocytes. The extracts show no cytotoxicity, restore cell viability by 3-fold relative to oxidatively stressed cells, and reduce apoptosis. Notably, two enriched peptidesNV10 and RI10demonstrated superior cytoprotective efficacy under oxidative stress. These peptides scavenge intracellular ROS (∼60% reduction), modulate Keap1-Nrf2 pathway components at mRNA levels (downregulating Keap1, upregulating Nrf2), and suppress apoptosis via regulation of caspase and Bcl-2 mRNA expression. Molecular docking predictions suggest that the peptides bind to Keap1, a negative regulator of Nrf2, thereby providing a potential mechanism for Nrf2 pathway activation. These findings suggest that the identified peptides are potential candidates for therapeutic development in skin protection applications.