Amphibian-Derived Peptide OA-AL14 Alleviates UVB-Induced Skin Photoaging via Autophagy Activation Mediated by the AMPK/mTOR Pathway.

Skin photoaging, primarily driven by ultraviolet B (UVB) radiation, is a complex process involving oxidative stress and autophagic dysfunction, for which effective therapeutic options remain limited. Here, we identified a novel peptide, OA-AL14 (ALFWPMKKPWPESC), from the skin secretions of the frog Odorrana andersonii Boulenger, 1882, and investigated its protective effects against UVB-induced photoaging. OA-AL14 exhibited excellent biocompatibility and potent antioxidant activity in vitro. In a UVB-irradiated mouse model, topical application of OA-AL14 significantly ameliorated key features of photoaging, including erythema, pigmentation, epidermal hyperplasia, and barrier disruption. Mechanistically, OA-AL14 activated the Nrf2 antioxidant pathway and restored cellular redox balance. Furthermore, transcriptomic and biochemical analyses revealed that OA-AL14 induced protective autophagy via the AMPK/mTOR signaling pathway. Inhibition of autophagy partially abrogated its protective effects, confirming the functional relevance of this mechanism. These findings establish OA-AL14 as a promising multifunctional candidate for treating skin photoaging by integrating antioxidant defense and autophagy activation.