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基于网络药理学的四君子汤治疗溃疡性结肠炎的作用机制及实验验证

[Mechanism and experimental verification of Sijunzi Decoction in treatment of ulcerative colitis based on network pharmacology].

作者信息

Meng-Long Zou, Xiao-Yan Huang, Ya-Lu Chen, Xin Ning, Qing-Ting Ruan, Zhen-Yi Luo, Li-Qun L I

机构信息

Graduate School of Guangxi University of Traditional Chinese Medicine Nanning 530001, China.

the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine Nanning 530023, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2020 Nov;45(22):5362-5372. doi: 10.19540/j.cnki.cjcmm.20200810.405.

Abstract

To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.

摘要

基于网络药理学探讨四君子汤治疗溃疡性结肠炎(UC)的作用机制。运用中药系统药理学数据库与分析平台(TCMSP)提取四君子汤的活性成分及相应靶点,并借助Uniprot数据库对靶点进行标准化处理。通过GeneCards数据库和Disgenet数据库获取UC的相关靶点,利用R语言筛选药物与疾病的交集靶点。运用Cytoscape软件构建四君子汤“活性成分-疾病靶点”可视化调控网络,通过STRING数据库构建蛋白质-蛋白质相互作用网络。在Bioconductor平台上进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并通过动物实验对部分靶点进行验证。通过数据库分析,共获得四君子汤135个活性成分、114个预测靶点以及与UC的80个共同靶点。核心靶蛋白包括白细胞介素6(IL-6)、半胱天冬酶-3(CASP3)、血管内皮生长因子A(VEGFA)、表皮生长因子受体(EGFR)等。GO功能富集分析涉及102项,主要影响转录因子活性、酶活性、受体活性及生化过程调控。KEGG通路富集分析表明,有120项参与人巨细胞病毒感染、癌症、凋亡、炎症等通路。小鼠实验表明,四君子汤可下调靶蛋白IL-6和CASP3的表达,抑制肠上皮细胞凋亡。四君子汤治疗UC是多成分、多靶点、多通路相互作用的结果。实验证明,四君子汤可能通过调节IL-6和CASP3的表达,参与凋亡、炎症等通路而发挥有效作用。

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