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基于网络药理学的干姜抗癌作用机制分析

Anti-cancer mechanism of Zingiberis Rhizoma based on network pharmacology
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摘要 目的采用网络药理学方法探究干姜的主要活性成分及其抗癌作用机制。方法在中药系统药理学分析平台(TCMSP)数据库中检索干姜的化学成分,根据'类药五原则'与'口服生物利用度'≥30%这一标准筛选干姜的活性成分,预测其活性成分对应的作用靶点,采用Cytoscape 3.2.1软件构建活性成分-预测靶点网络图。在Genecards数据库中以'anti-cancer'为关键词搜索抗癌靶点,与干姜靶点映射筛选出共同靶点作为干姜的抗癌靶点。将干姜抗癌靶点导入STRING数据库中进行蛋白质-蛋白质相互作用分析,构建靶蛋白相互作用网络图(PPI),利用Cytoscape3.2.1的'CytoNCA'插件筛选干姜的抗癌核心靶点。使用DAVID数据库及Cytoscape3.2.1的'GlueGO'插件对干姜抗癌靶点进行KEGG信号通路富集分析和GO生物过程富集分析,并构建干姜活性成分-核心抗癌靶点-信号通路网络图。结果获得干姜中具有类药性、口服吸收良好的活性成分52种,对应靶点101个。其中抗癌靶点39个,核心靶点10个。KEGG富集分析得到与干姜抗癌作用有关的信号通路68条,主要涉及肿瘤坏死因子(TNF)信号通路、血管内皮生长因子(VEGF)信号通路等。GO富集分析得出与干姜抗癌作用有关的生物过程35个,主要涉及到一氧化氮生物合成、细胞增殖与凋亡等。结论本研究初步揭示了干姜的药效物质基础及其可能的抗癌作用机制,为干姜抗癌研究提供参考。 Objective To explore the active components and the anti-cancer mechanism of Zingiberis Rhizoma by network pharmacology.Methods The components of Zingiberis Rhizoma were searched through the Chinese Medicine System Pharmacology(TCMSP)database.The active components of Zingiberis Rhizoma were screened with'Lipinski rule'and'Oral Bioavailability≥30%'rules,the corresponding targets of the active components were predicted.Cytoscape 3.2.1 was used to build a network between components and targets.Anti-cancer targets were searched from Genecards database with the keyword'anticancer',the anti-cancer targets was mapped to the targets of Zingiberis Rhizoma to screen out the common targets as the anti-cancer targets of Zingiberis Rhizoma.The anti-cancer targets of Zingiberis Rhizoma were imported into STRING database for proteinprotein interaction analysis,and the target protein interaction network graph(PPI)was constructed.Cytoscape 3.2.1'CytoNCA'plug-in unit was used to screen the key anti-cancer targets of Zingiberis Rhizoma.DAVID database and Cytoscape 3.2.1'ClueGO'plug-in unit were used to perform KEGG pathway enrichment analysis and GO biological process enrichment analysis,and build active ingredients-key anticancer targets-KEGG pathway network map.Results 52 components and 101 corresponding targets of Zingiberis Rhizoma with drug-like properties and good oral absorption were obtained.Among them,there were 39 targets with anticancer effects and 10 key anti-cancer targets.KEGG signaling pathway analysis of anti-cancer targets of Zingiberis Rhizoma obtained 68 signaling pathways,mainly related to TNF signaling pathway and VEGF signaling pathway,etc.GO biological process analysis obtained 35 biological processes,mainly involved in nitric oxide biosynthesis,cell proliferation and apoptosis,etc.Conclusion This study preliminarily revealed the pharmacodynamic substance basis of Zingiberis Rhizoma and its possible anticancer pharmacological effects,providing basis for anti-cancer research of Zingiberis Rhizoma.
作者 耿胜男 杨莉 李阳杰 杜钢军 GENG Shengnan;YANG Li;LI Yangjie;DU Gangjun(Zhengzhou University of Industry Technology,Zhengzhou 451150,China;Institute of Pharmacy,Pharmacy College of Henan University,Kaifeng 475004,China)
出处 《药物评价研究》 CAS 2019年第9期1730-1740,1748共12页 Drug Evaluation Research
基金 河南省自然科学基金资助项目(182300410310) 郑州工业应用技术学院校级科研项目(2018YB021).
关键词 网络药理学 干姜 抗癌 靶点 信号通路 Network pharmacology Zingiberis Rhizoma anti-cancer targets signaling pathway
作者简介 第一作者:耿胜男(1994—),女,硕士,讲师,从事中药药理及肿瘤药理学研究。Tel:16637100686 E-mail:1017172540@qq.com;通信作者:杜钢军,男,博士,教授,博士生导师,从事中药药理及肿瘤药理学研究。Tel:15037883506 E-mail:gsnwjie@163.com
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