Abstract：
Ultraviolet (UV)-induced skin photoaging is caused by qualitative and quantitative degradation of dermal extracellular matrix components such as collagen and elastic fibers. Elastic fibers are important for maintaining cutaneous elasticity, despite their small amount in the skin. Previously, microfibril-associated protein 4 (MFAP-4), which is downregulated in photoaging dermis, has been found to be essential for elastic fiber formation by interaction with both fibrillin-1 and elastin, which are core components of elastic fiber. In addition, enhanced cutaneous MFAP-4 expression in a human skin-xenografted murine photoaging model protects against UV-induced photodamage accompanied by the prevention of elastic fiber degradation and aggravated elasticity. We therefore hypothesized that the upregulation of MFAP-4 in dermal fibroblasts may more efficiently accelerate elastic fiber formation. We screened botanical extracts for MFAP-4 expression-promoting activity in normal human dermal fibroblasts (NHDFs). We found that rosemary extract markedly promotes early microfibril formation and mature elastic fiber formation along with a significant upregulation of not only MFAP-4 but also fibrillin-1 and elastin in NHDFs. Furthermore, rosmarinic acid, which is abundant in rosemary extract, accelerated elastic fiber formation via upregulation of transforming growth factor β-1. This was achieved by the induction of cAMP response element-binding protein phosphorylation, demonstrating that rosmarinic acid represents one of the active ingredients in rosemary extract. Based on the findings in this study, we conclude that rosemary extract and rosmarinic acid represent promising materials that exert a preventive or ameliorative effect on skin photoaging by accelerating elastic fiber formation.
摘要：
紫外线（UV）诱导的皮肤光老化是由真皮细胞外基质成分如胶原蛋白和弹性纤维的定性和定量降解引起的。弹性纤维对保持皮肤弹性很重要,尽管它们在皮肤中的少量。以前,微纤维相关蛋白4（MFAP-4），在光老化真皮中下调，已发现通过与原纤维蛋白-1和弹性蛋白相互作用而形成弹性纤维是必不可少的，是弹性纤维的核心部件。此外,在人皮肤异种移植鼠光老化模型中增强的皮肤MFAP-4表达可防止紫外线引起的光损伤，并防止弹性纤维降解和弹性恶化。因此,我们假设真皮成纤维细胞中MFAP-4的上调可以更有效地加速弹性纤维形成。我们筛选了植物提取物在正常人真皮成纤维细胞（NHDF）中的MFAP-4表达促进活性。我们发现迷迭香提取物显着促进早期微纤丝形成和成熟弹性纤维形成，并且不仅显著上调MFAP-4，而且显著上调NHDF中原纤维蛋白-1和弹性蛋白。此外，迷迭香酸,富含迷迭香提取物，通过上调转化生长因子β-1加速弹性纤维的形成。这是通过诱导cAMP反应元件结合蛋白磷酸化来实现的，证明迷迭香酸是迷迭香提取物中的活性成分之一。根据这项研究的结果，我们得出的结论是迷迭香提取物和迷迭香酸代表了有希望的材料，通过促进弹性纤维的形成对皮肤光老化发挥预防或改善作用。
