Abstract: This study explored the protective effects and potential mechanisms of bioactive peptides derived from giant salamanders against H2O2-induced aging. To this end, zebrafish larvae survival rates, heart rates, radical scavenging capacity, reactive oxygen species (ROS) levels, senescence-associated β-galactosidase (SA-β-gal) activity, and senescence-related protein expression were measured. Meanwhile, the activities of superoxide dismutase, catalase, and glutathione were determined along with malondialdehyde content. The results indicated that compared with the control group, the survival rate of larvae in the aging model group decreased to 58.67%, while treatment with 125 μg/mL of the peptides increased it to 94%. In the treatment group, ROS levels approached normal values, antioxidant enzyme activity was enhanced, apoptosis levels were reduced, and the activity of aging-related enzymes was inhibited. Western blot analysis further revealed that intervention with giant salamander-derived bioactive peptides downregulated the expression of the key aging biomarkers P53 and P21, as well as related proteins such as phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), p-PI3K, and p-AKT. These findings suggest that the peptides exert potent protective effects against H2O2-induced aging in zebrafish, potentially through mechanisms involving inhibition of H2O2-induced apoptosis, enhancement of antioxidant capacity, and regulation of apoptosis-related protein expression. This study provides a theoretical basis for the development of high-value-added products from giant salamander-derived bioactive peptides.

Key words: giant salamander-derived bioactive peptide; H2O2; zebrafish; phosphoinositide 3-kinase/protein kinase B; aging