Scopoletin downregulates MMP­1 expression in human fibroblasts via inhibition of p38 phosphorylation.

Irradiation of keratinocytes by ultraviolet B induces cytokine production, which in turn activates fibroblasts to produce cytokines and increase matrix metallopeptidase (MMP)­1 protein expression. The present study investigated the effect and potential mechanisms of scopoletin on the regulation of MMP­1 expression in fibroblasts. Scopoletin was isolated from Artemisia capillaris crude extract. Treatment of fibroblasts with scopoletin resulted in a decrease in the protein expression of MMP­1 following stimulation with human keratinocyte (HaCaT) conditioned medium. To further explore the mechanism underlying this effect, the expression levels of proteins in the mitogen­activated protein kinase (MAPK) and nuclear factor­κB (NF­κB) signaling pathways were evaluated via western blot analysis. The mRNA expression levels of interleukin (IL)­1α and tumor necrosis factor (TNF) α were evaluated via reverse transcription­quantitative polymerase chain reaction. The effect of scopoletin on cell viability was assessed with the MTT assay. The results demonstrated that scopoletin treatment markedly decreased MMP­1, IL­1α and TNFα mRNA expression in fibroblasts stimulated with HaCaT conditioned medium (40 mJ/cm2), without any apparent cell cytotoxicity, and in a dose­dependent manner. In addition, western blot analysis demonstrated that scopoletin reduced the phosphorylation of p38 MAPK in fibroblasts. In summary, the present study demonstrated that scopoletin inhibited MMP­1 and proinflammatory cytokine expression by inhibiting p38 MAPK phosphorylation. These findings suggest that scopoletin may have potential as a therapeutic agent to prevent and treat photoaging of the skin.