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基于网络药理学与分子对接技术探讨姜黄素治疗矽肺的作用机制
Exploring the mechanism of action of curcumin in the treatment of silicosis based on network pharmacology and molecular docking
【摘要】 目的 通过网络药理学结合分子对接技术探讨姜黄素治疗矽肺的作用机制。方法 基于多个数据库收集姜黄素与矽肺靶点,建立姜黄素治疗矽肺的靶点预测网络,将共同靶点提交STRING数据库,采用Cytoscape软件分析连通度,对排序前20的基因进行基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析,对获取的靶点进行分子对接,研究姜黄素治疗矽肺的作用机制。结果 从数据库中获取了311个与姜黄素相关的靶点,270个与矽肺相关的靶点,74个姜黄素与矽肺的共同靶点。GO功能分析显示,这些靶点与2 665个通路相关;KEGG通路富集分析显示了188个相关通路。分子对接结果显示,姜黄素与丝裂原活化蛋白激酶3(MAPK3)、白细胞介素(IL)6、丝氨酸/苏氨酸激酶1(AKT1)、血管内皮生长因子A(VEGFA)、信号转导与转录激活因子3、白蛋白、Jun原癌基因、肿瘤坏死因子(TNF)、IL1B、肿瘤蛋白p53、C-C基序趋化因子配体2和纤连蛋白1等靶点均具有良好的结合能力。结论 姜黄素对矽肺的治疗作用是通过多靶点及多通路共同实现的;具体而言,姜黄素可能通过与核心靶点MAPK3、IL6、AKT1、VEGFA和TNF结合,调节MAPK、IL6、TNF、磷脂酰肌醇3-激酶/蛋白激酶B和VEGF等信号通路,从而发挥治疗矽肺的作用。
【Abstract】 Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology(GO) function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways.Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3(MAPK3), interleukin(IL) 6, serine/threonine kinase 1(AKT1), vascular endothelial growth factor A(VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor(TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.
【Key words】 Curcumin; Silicosis; Network pharmacology; Molecular docking; Target; Signaling pathway; Mechanism of action;
- 【文献出处】 中国职业医学 ,China Occupational Medicine , 编辑部邮箱 ,2023年04期
- 【分类号】R135.2
- 【下载频次】39