Colla Corii Asini regulate collagen regeneration in UV exposure-induced skin photoaging in mice.

BACKGROUND: Ultraviolet (UV) radiation is the primary external factor driving skin aging, mainly due to imbalanced collagen synthesis and degradation. Identifying new drugs targeting collagen regeneration may effectively delay skin aging. Colla Corii Asini (CCA), derived from donkey skin, contains abundant proteins and peptides, suggesting potential benefits against photoaging through collagen homeostasis regulation. However, its mechanisms and active components remain unclear. OBJECTIVE: This study aimed to evaluate whether CCA mitigates photoaging by regulating collagen synthesis and degradation, identifying its active components and molecular targets to support future pharmacological studies. METHODS: A photoaging mouse model was established, and the therapeutic effects of CCA were assessed through in vivo optical imaging and ex vivo analyses. Human dermal fibroblasts were employed to explore mechanisms of collagen regulation by CCA. PPI analysis and AlphaFold3 were used to predict and validate key active peptides and molecular targets. RESULTS: CCA significantly improved the structure and appearance of photoaged skin, reduced oxidative stress and inflammation, and enhanced collagen content and density. Mass spectrometry identified 98 peptides closely linked to protein synthesis. Mechanistically, CCA increased collagen synthesis and reduced aging markers by activating the TGFβ-SMAD signaling pathway, balancing MMPs and TIMPs. Importantly, this effect is primarily associated with the core CCA peptide YYTSASGDEMVSLK binding to and upregulating TGFBR1 and TGFBR2 expression, activating the TGFβ-SMAD pathway, and promoting collagen regeneration. CONCLUSION: CCA, particularly peptide YYTSASGDEMVSLK, has potential to slow skin photoaging, highlighting a promising therapeutic strategy for skin aging management.