Soft-shelled turtle-derived antioxidant peptides inhibit advanced glycation end products (AGEs) formation and mitigate AGE-induced damage to HUVECs via the AGEs/RAGE signaling pathway

Advanced glycation end products (AGEs) may trigger oxidative stress, resulting in atherosclerotic plaques. This study investigated the effects of soft-shelled turtle-derived antioxidant peptides on glucose-related protein glycation. Our results indicate seven antioxidant peptides derived from soft-shelled turtle have inhibitory effects on the AGEs formation, especially for N-3-A. To study the potential protective impacts of N-3-A against AGEs-induced damage, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels were measured. Interestingly, cells treated with N-3-A show significant upregulation of GSH-Px, SOD, and CAT activities while down-regulate the content of oxidative damage marker-MDA. Mechanistically, molecular docking analysis showed the interaction pattern between N-3-A and C-terminal domain of receptor for advanced glycation end products (RAGE). We identified five hydrogen bonds between the active peptides, highlighting arginine as the primary inhibitory site. It demonstrated N-3-A can protect against AGEs-induced health disorders through inhibiting the activation of NF-κB signaling pathway. • Seven antioxidant peptides have been obtained from the soft-shelled turtle protein. • N-3-A shows the highest inhibitory effect on the formation of AGEs in vitro. • N-3-A alleviates downstream changes of GSH-Px, SOD, CAT, MDA, and ROS caused by AGEs. • N-3-A suppresses the NF-κB signaling pathway through interaction with AGEs receptor.