Ginsenoside Rh1 ameliorates UV-induced skin aging by regulating oxidative stress via the Sirt3/Nrf2/HO-1 pathway

Skin aging is a complex pathological process mediated by a combination of endogenous metabolic dysregulation and exogenous ultraviolet (UV) radiation, with oxidative stress due to excessive accumulation of reactive oxygen species (ROS) as the central driver. Rare ginsenoside Rh1 is a natural compound with antioxidant and anti-inflammatory properties, but its mechanism of action in UV-induced skin photoaging remains unclear. This study aims to investigate the protective effect of Rh1 against UV-induced skin aging and the underlying molecular mechanisms. All animal experiments were approved by the Animal Ethics Committee of West China Hospital, Sichuan University (approval number: 20241230001). To evaluate the anti-photoaging effect of Rh1, we established photoaging models in BALB/c mice and human dermal fibroblasts (HDF). In vivo experiments showed that Rh1 (25 and 50 μmol·L^-1) significantly alleviated UV-induced skin thickening, erythema, and moisture loss, reduced the expression of pro-apoptotic protein Bax, and up-regulated anti-apoptotic protein Bcl-2. In vitro experiments indicated that Rh1 (12.5, 25, and 50 μmol·L^-1) reduced UVB (UV wavelength 280-320 nm)-induced ROS accumulation, oxidative damage, and the proportion of senescence-associated β-galactosidase (SA-β-Gal) positive cells. Mechanistic studies demonstrated that Rh1 promotes nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation by activating sirtuin 3 (Sirt3), thereby upregulating downstream heme oxygenase-1 (HO-1) expression. Sirt3 siRNA experiments confirmed that gene silencing can blocks Rh1 from activating the Nrf2/HO-1 pathway, weakening its ability to inhibit ROS production and delay cellular aging. In summary, Rh1 alleviates UV-induced oxidative damage and skin aging through the Sirt3/Nrf2/HO-1 signaling axis, providing a new strategy for the development of anti-photoaging drugs targeting the antioxidant pathway.