Effect of Zanthoxylum piperitum Extract on Human Skin Protection from UVB by Regulation of COP1 and PPAR-α

김윤선, 김유미, 이상화
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Abstract

Ultraviolet (UV) irradiation from the sun is the primary environmental factor that causes skin damages including skin cancer and premature skin aging. Because, even the most powerful sunscreen can’t always afford enough protection, it is necessary to enhance the defensive power of skin against UV. Recently, constitutive photomorphogenic protein-1 (COP1) has shown to contribute to the regulation of UVB response of keratinocytes. In this study, we represent that COP1 and its associated protein, de-etiolated 1 (DET1), might participate in photoaging process in human skin as Arabidopsis COP1 does sun-protective function in plants. After UVB irradiation, the decrease of COP1 and DET1 mRNA expression was followed by the increase of c-Jun total protein. Moreover, transfection with DNA vectors expressing COP1 and DET1 down-regulated the c-Jun total protein. We found that Zanthoxylum piperitum extract (ZE) up-regulated the expression of COP1 and DET1 on human keratinocytes, and inhibited the expression of MMP1 which is one of the genes regulated by c-Jun signal. In addition, ZE has been reported to stimulate PPAR-α and strengthen the skin barrier. We found that ZE decreased the UVB-induced IL-6 and IL-8 in NHEK cells. In human study, ZE protected skin against UV-B induced erythema and erythema-induced pigmentation. These results indicate that ZE could be useful for the protection against the adverse effects of UV irradiation through various mechanisms.
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花椒提取物通过调节COP1和PPAR-α对人体皮肤抗UVB的保护作用
来自太阳的紫外线(UV)照射是导致皮肤癌和皮肤过早老化等皮肤损伤的主要环境因素。因为,即使是最强大的防晒霜也不能总是提供足够的保护,所以有必要增强皮肤对紫外线的防御能力。最近,组成型光形态形成蛋白-1 (COP1)被证明参与了角化细胞对UVB反应的调节。在这项研究中,我们认为COP1及其相关蛋白去黄化1 (DET1)可能参与了人类皮肤的光老化过程,就像拟南芥COP1在植物中具有防晒功能一样。UVB照射后,COP1和DET1 mRNA表达降低,c-Jun总蛋白升高。此外,转染表达COP1和DET1的DNA载体可下调c-Jun总蛋白。我们发现花椒提取物(ZE)上调人角质形成细胞COP1和DET1的表达,抑制c-Jun信号调控基因之一MMP1的表达。此外,据报道,ZE可以刺激PPAR-α并增强皮肤屏障。我们发现,ZE降低了uvb诱导的NHEK细胞中IL-6和IL-8的表达。在人体研究中,ZE保护皮肤免受UV-B诱导的红斑和红斑诱导的色素沉着。这些结果表明,ZE可能通过多种机制对紫外线照射的不良反应有保护作用。
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