Salidroside ameliorates skin aging in male mice by promoting collagen regeneration via modulation of FOS and MMP9.

Salidroside, a phenolic compound derived from Rhodiola rosea L., has been widely utilized in cosmetics and medicine for its anti-melanogenic properties. However, its role in collagen regeneration during skin aging remains unclear. In this study, we investigated the effects of salidroside on collagen synthesis and explored its underlying mechanisms in a murine model of skin aging. Administering salidroside (20, 40, and 80 mg/kg) orally for 28 days significantly increased dermal thickness, collagen volume, and the expression of collagen I and III in male mouse skin. Bioinformatic analysis of RNA-seq data from the GSE278079 dataset revealed enhanced neutrophil infiltration in aged skin, suggesting a role for inflammatory processes in skin aging. Furthermore, salidroside up-regulated the expression of the transcription factor FOS and down-regulated matrix metalloproteinase MMP9, both in vivo and in L929 fibroblasts. These changes correlated with reduced collagen degradation and enhanced fibroblast activity. Crucially, siRNA-mediated silencing of Fos in vitro partially diminished the salidroside-induced upregulation of collagen expression, substantiating a causal regulatory role for FOS in this process. Our results demonstrate that salidroside promotes collagen regeneration and mitigates skin aging, which is closely associated with the attenuation of neutrophil-mediated inflammation, alongside the upregulation of FOS and downregulation of MMP9. These findings highlight the therapeutic potential of salidroside in combating age-related skin changes.