Abstract

Pro-Xylane enhances cell viability, reduces apoptosis, and inhibits reactive oxygen species (ROS) production in UVB-irradiated HaCaT cells, while also reversing UVB-induced upregulation of senescence markersand senescence-associated secretory phenotype (SASP) levels. • SGK1 is confirmed as a critical target mediating Pro-Xylane’s protective effects against UVB-induced skin damage. • Pro-Xylane exerts its anti-senescence function by promoting ubiquitination of p21 at the K141 site and retaining p21 in the cytoplasm, which counteracts UVB-induced accumulation of p21 in the nucleus. • In vivo experiments using UVB-irradiated rats confirm Pro-Xylane’s ability to support skin regeneration, highlighting its promising role as a candidate for skin repair and anti-aging treatments. Background Ultraviolet B (UVB) radiation causes skin damage, leading to aging and inflammatory responses. Pro-Xylane, a plant-derived compound, has been proposed for its potential protective effects against UVB-induced skin damage. However, its molecular mechanisms, particularly regarding cellular senescence, remain unclear. Methods HaCaT cells were exposed to UVB radiation and treated with Pro-Xylane. The effects on cell viability, apoptosis, reactive oxygen species (ROS) production, senescence markers, and collagen expression were assessed via CCK-8, TUNEL staining, DCFH-DA, and immunofluorescence assays. GEO datasets identified SGK1 as a key target. The p21 ubiquitination and subcellular localization were analyzed via immunoprecipitation and Western blot. In vivo experiments were conducted using UVB-irradiated rats to confirm the therapeutic effects of Pro-Xylane on skin regeneration. Results Pro-Xylane improved cell viability and inhibited ROS production in UVB-exposed HaCaT cells. Pro-Xylane decreased β-galactosidase expression and reversed UVB-induced upregulation of p21. SGK1 was identified as a key mediator in the protective effects. Pro-Xylane promoted mitochondrial function, and reduce