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Int J Mol Med. 2018 Oct;42(4):2285-2293. doi: 10.3892/ijmm.2018.3757. Epub 2018 Jul 4.

Scopoletin downregulates MMP‑1 expression in human fibroblasts via inhibition of p38 phosphorylation.

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Interdisciplinary Program of Biomodulation, Myongji University, Yongin, Gyeonggi 17058, Republic of Korea.
Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin, Gyeonggi 17058, Republic of Korea.
Department of Biotechnology, Chonnam National University, Yeosu, Chonnam 59626, Republic of Korea.


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 MMP‑1 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 MMP‑1 following stimulation with human keratinocyte (HaCaT) conditioned medium. To further explore the mechanism underlying this effect, the expression levels of proteins in the mitogen‑activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) 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 transcription‑quantitative polymerase chain reaction. The effect of scopoletin on cell viability was assessed with the MTT assay. The results demonstrated that scopoletin treatment markedly decreased MMP‑1, IL‑1α and TNFα mRNA expression in fibroblasts stimulated with HaCaT conditioned medium (40 mJ/cm2), without any apparent cell cytotoxicity, and in a dose‑dependent 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 MMP‑1 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.

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