Skin secretion of Andrias davidianus aqueous extract delays skin aging by suppressing the MAPK pathway

Skin aging, a prominent manifestation of organismal senescence, is closely associated with the accumulation of endogenous reactive oxygen species (ROS). This study investigated the anti-skin-aging effects of skin secretion of Andrias davidianus (SSAD) using in vitro models of human skin fibroblast (HSF) senescence induced by D-galactose (D-Gal) or ultraviolet B (UVB) irradiation and an in vivo murine model of UVB-induced photoaging. Our findings demonstrate that in vitro , SSAD aqueous extract pretreatment not only mitigated D-Gal/UVB-induced cell death and senescence by enhancing HSF proliferation and migration but also effectively attenuated intracellular ROS overproduction and DNA damage, while upregulating key antioxidant enzymes, including GPX-1 and SOD-1. In vivo , SSAD ameliorated UVB-induced dermal thickening, capillary dilation, and collagen degradation, and upregulated P21 expression. Mechanistically, the anti-aging efficacy of SSAD appears to be mediated by a multi-targeted action that suppresses ROS generation, inhibits MAPK signaling pathway activation, and promotes antioxidant enzyme expression. In conclusion, SSAD emerges as a promising natural agent capable of mitigating skin aging by concurrently targeting oxidative stress and modulating the MAPK pathway.