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利用网络药理学和体外研究揭示姜黄素的分子靶点及其在抑制皮肤炎症中的潜力。

Unraveling the Curcumin's Molecular Targets and Its Potential in Suppressing Skin Inflammation Using Network Pharmacology and In Vitro Studies.

作者信息

Sureshbabu Anjana, Smirnova Elena, Tuong Do Thi Cat, Vinod Sangeetha, Chin Sungyeon, Moniruzzaman Mohammad, Senthil Kalaiselvi, Lee Dong I, Adhimoolam Karthikeyan, Min Taesun

机构信息

Department of Animal Biotechnology, Jeju International Animal Research Center (JIA), Sustainable Agriculture Research Institute (SARI), Jeju National University, Jeju, Republic of Korea.

Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute of Home Science and Higher Education for Women, Coimbatore, Tamil Nadu, India.

出版信息

Drug Dev Res. 2025 Feb;86(1):e70058. doi: 10.1002/ddr.70058.

DOI:10.1002/ddr.70058
PMID:39943799
Abstract

Curcumin, a polyphenol compound derived from turmeric, has garnered attention for its anti-inflammatory and antioxidant properties, making it a promising candidate for treating skin inflammation. Despite its potential, the underlying pharmacological effects to skin inflammation remain unclear. Therefore, this study aimed to reveal the curcumin's molecular targets and its potential in suppressing skin inflammation using network pharmacology and in vitro experiments. A total of 7,393 and 239 targets related to curcumin and skin inflammation, respectively, were obtained from public databases. By drawing a Venn diagram, 216 common targets were identified as candidate targets. These targets were subjected to gene function and pathway enrichment analyses, and a protein-protein interaction network was established to investigate curcumin's impact on inflammation. The gene functions were mainly associated with inflammatory response, membrane raft, and serine-type endopeptidase activity. The NF-κB and MAPK pathways could be the major pathways through which curcumin acts on skin inflammation. Ten major targets of curcumin in the treatment of skin inflammation were identified: AKT1, TNF, EGFR, APP, MMP9, STAT3, HIF1A, PTGS2, EP300, and GSK3B. Molecular docking analysis results showed high binding affinity of curcumin to PTGS2, GSK3B, HIF1A, and STAT3, which may contribute to its inhibitory effect on skin inflammation. In vitro experiments confirmed curcumin's anti-inflammatory effect on inflammation by reducing the expression levels of NO, IL-1β, and IL-6 in LPS-induced HaCaT cells. Taken together, this study reveals major targets and pathways of curcumin in the treatment of skin inflammation, paving the way for invivo and clinical investigations.

摘要

姜黄素是一种从姜黄中提取的多酚化合物,因其抗炎和抗氧化特性而受到关注,使其成为治疗皮肤炎症的有潜力的候选物。尽管具有潜在价值,但其对皮肤炎症的潜在药理作用仍不清楚。因此,本研究旨在利用网络药理学和体外实验揭示姜黄素的分子靶点及其在抑制皮肤炎症方面的潜力。分别从公共数据库中获得了总共7393个与姜黄素相关的靶点和239个与皮肤炎症相关的靶点。通过绘制维恩图,确定了216个共同靶点作为候选靶点。对这些靶点进行基因功能和通路富集分析,并建立蛋白质-蛋白质相互作用网络以研究姜黄素对炎症的影响。基因功能主要与炎症反应、膜筏和丝氨酸型内肽酶活性相关。NF-κB和MAPK通路可能是姜黄素作用于皮肤炎症的主要通路。确定了姜黄素治疗皮肤炎症的十个主要靶点:AKT1、TNF、EGFR、APP、MMP9、STAT3、HIF1A、PTGS2、EP300和GSK3B。分子对接分析结果表明姜黄素与PTGS2、GSK3B、HIF1A和STAT3具有高结合亲和力,这可能有助于其对皮肤炎症的抑制作用。体外实验通过降低脂多糖诱导的HaCaT细胞中NO、IL-1β和IL-6的表达水平,证实了姜黄素对炎症的抗炎作用。综上所述,本研究揭示了姜黄素治疗皮肤炎症的主要靶点和通路,为体内和临床研究铺平了道路。

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