Stemonine Alleviates UVB-Induced Keratinocyte Senescence by Activating SIRT3

Ultraviolet B (UVB) radiation is the primary environmental factor contributing to skin damage, largely by accelerating cellular senescence, which leads to impaired skin function and premature aging. Recent studies have indicated that Stemonine, a natural alkaloid, has therapeutic potential owing to its documented biological activities. In this study, we investigated the protective effects of Stemonine on immortalized human keratinocyte cell line HaCaT against UVB-induced cellular senescence and elucidated the underlying mechanisms. Our results demonstrated that Stemonine significantly improved cell viability, attenuated oxidative stress, and ameliorated mitochondrial dysfunction in UVB-irradiated HaCaT cells. Furthermore, Stemonine treatment reduced DNA damage signaling, downregulated key senescence executors such as acetylated p53 and p21, and decreased SA-β-Gal activity. Importantly, Stemonine upregulated both the expression and activity of SIRT3. Crucially, the protective effects of Stemonine were largely abolished upon SIRT3 knockdown, indicating that its actions are mediated via the SIRT3 pathway. These findings suggest that Stemonine is a promising candidate for mitigating UVB-induced skin aging.