A yak bone collagen-derived antioxidant peptide with excellent stability alleviates UVA-induced photoaging by activating the Keap1/Nrf2 signaling pathway

Abstract

Background: Prolonged exposure to ultraviolet A (UVA) rays can trigger oxidative stress, leading to skin photoaging. Our team previously identified four antioxidant peptides derived from yak bone collagen through bioinformatics prediction. The objective of this study was to screen out one most promising application antioxidant peptide through molecular docking, in vitro antioxidant activity verification and stability assessment, and elucidate its mechanism of action. Results: The results of molecular docking studies suggested that GGGPPGPM (P1) could effectively bind to the key protein Keap1 in the antioxidant signaling pathway. The in vitro screening results indicated that P1 exhibited the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (83.42 ± 3.07%) and Fe2+ chelating ability (69.25 ± 6.10%) at a concentration of 1 mg mL−1. Additionally, with the exception of a few conditions, P1 retained more than 90% DPPH radical scavenging activity across a wide range of temperature, pH, metal ions and typical processing aids. Cellular results indicated that P1 significantly reduced the production of reactive oxygen species and malonaldehyde in UVA-damaged cells, and elevated the levels of superoxide dismutase and catalase. It was found that the Keap1/Nrf2 signaling pathway in the UVA-damaged photoaging cells was modulated under P1 intervention, significantly increasing the expression of NAD(P)H dehydrogenase quinone 1 and heme oxygenase-1. In addition, P1 notably enhanced the mRNA expression level of tissue inhibitor of metal protease 1 and collagen I and decreased the mRNA expression levels of matrix metalloproteinase-1. Conclusion: These findings demonstrated that P1 derived from yak bone collagen presents a promising therapeutic candidate for mitigating skin photoaging. An animal model might be employed for further examination to corroborate these findings. © 2025 Society of Chemical Industry.