Abstract

With the growing prominence of skin photodamage caused by ultraviolet (UV) radiation, the development of efficient and safe natural photoprotectants has become a major research focus. Ginsenoside Re (G-Re), a primary active component of ginseng (Panax ginsengC. A. Mey.), has attracted much attention due to its significant antioxidant and anti-inflammatory activities; however, its systemic role and mechanism in protecting against photodamage remain unclear. In this study, a UVB-induced rat photodamage model was established to evaluate the protective effect of ginsenoside Re through histopathological staining, biochemical assay, and immunohistochemical analysis. Furthermore, an integrated transcriptomic and metabolomic approach was applied to elucidate the molecular mechanism of G-Re protection and to establish the association between the photodamage phenotype, metabolic pathways, and gene functions. Following their identification via integrated multi-omics analysis, the key targets were subjected to verification via Western blotting. The results showed that G-Re could effectively alleviate UVB-induced pathological injury and reduce the level of oxidative stress and inflammatory factors, which could reverse regulate the abnormal expression of 265 differential genes and 30 metabolites. The glutathione metabolism pathway was proven as a key pathway mediating the protective effects of ginsenoside Re against skin photodamage via integrated analysis, WB verification, and molecular docking. The current study indicated that G-Re could be a promising natural sunscreen additive in cosmetical products.