基于网络药理学与分子对接的黄芩-白芍治疗慢性结肠炎的研究  

Research on the Treatment of Chronic Colitis with Scutellaria baicalensis Georgi and Radix Paeoniae Alba Based on Network Pharmacology and Molecular Docking

作　　者：房城 郑秀茜 徐晓敏 刘树民[2] Fang Cheng;Zheng Xiuxi;Xu Xiaomin;Liu Shumin(Drug Safety Evaluation Center,Heilongjiang University of Chinese Medicine,Harbin 150040,China;Institule of Traditional Chinese Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学药物安全性评价中心,哈尔滨150040 [2]黑龙江中医药大学中医药研究院,哈尔滨150040

出　　处：《中国药师》2021年第9期1594-1600,共7页China Pharmacist

基　　金：国家重点基础研究发展计划(973计划)项目(编号:2013CB531804);黑龙江中医药大学优秀创新人才(领军人才)项目(编号:2018RCL13)。

摘　　要：目的:探讨黄芩-白芍药对治疗慢性结肠炎的作用机制。方法:采用中药系统药理学分析平台(TCMSP)对黄芩、白芍活性成分进行收集、筛选,并对活性成分潜在靶点进行预测与筛选,用Cytoscape 3.6.1软件构建活性成分-潜在靶点网络;用DisGeNET数据库预测慢性结肠炎的作用靶点,将其导入蛋白质相互作用网络数据库(STRING 11.0)分析其靶点蛋白质-蛋白质的相互作用(PPI),导入Cytoscape 3.6.1软件构建慢性结肠炎相关的PPI网络。用Merge工具将黄芩-白芍药对活性成分-作用靶点网络与慢性结肠炎的靶点PPI网络进行合并,构建黄芩-白芍药对活性成分-潜在靶点网络。用ClueGo插件进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,并绘制活性成分-作用靶点-信号通路作用网络。选取PPI网路度值前3的蛋白与黄芩-白芍共有成分以及成分靶点网络度值靠前的10个成分进行分子对接验证,在Protein Data Bank数据库中检索获得受体蛋白白细胞介素6(IL-6)、过氧化物酶体增殖物激活受体γ(PPARg)、肿瘤坏死因子(TNF),利用PyMOL 2.3.4软件对受体蛋白进行去水、去配体等操作,采用AutoDockTools软件对12个受体蛋白进行加氢、平衡电荷等修饰,用Grid程序对每个受体蛋白进行处理,利用AutoDock Vina 1.1.2对3个受体蛋白与10个主要配体小分子分别进行分子对接,通过结合能评分对受体与配体的结合进行初步验证。结果:得到黄芩-白芍药对治疗慢性结肠炎潜在活性成分31个,作用靶点11个,分别为对氧磷酶1(PON1)、芳香烃受体(AhR)、过氧化氢酶(CAT)、纤维连接蛋白1(FN1)、前列腺素内过氧化物合酶2(PTGS2)、磷酸肌醇-3-激酶(PIK3CG)、PPARg、趋化因子CCL2、肿瘤蛋白p53(TP53)、IL-6、TNF。GO功能富集分析得到有8条生物学过程,KEGG通路注释分析获得肌萎缩性脊髓侧索硬化症(ALS)、白细胞介素-17信号通路(IL-17 signaling pathway)、糖尿�Objective:To research the mechanism of Scutellaria baicalensis Georgi and Radix Paeoniae Alba in the treatment of chronic colitis.Methods:The TCM System Pharmacology Analysis Platform(TCMSP)was used to collect and screen the active ingredients of Scutellaria baicalensis Georgi and Radix Paeoniae Alba,predict and screen the potential targets of the active ingredients,and the Cytoscape 3.6.1 software was used to construct a network of active ingredients-potential targets.The DisGenet database was used to predict the targets of chronic colitis,which was imported into the protein interaction network database(STRING 11.0)to analyze the target protein-protein interaction(PPI),and Cytoscape(3.6.1)software was imported to construct the PPI network related to chronic colitis.The Merge tool was used to merge the active ingredient-target network of Scutellaria baicalensis Georgi-Radix Paeoniae Alba,and the PPI network of chronic colitis was applied to construct a network of active ingredients-potential targets of Scutellaria baicalensis Georgi-Radix Paeoniae Alba.The Clue Go plug-in was used to carry out gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and to map the component-target-signal pathway network.The top 3 proteins of the PPI network degree value and the common components of Scutellaria baicalensis Georgi-Radix Paeoniae Alba and the top 10 components of the component target network degree value were selected for molecular docking verification.The receptor protein interleukin 6(IL-6),peroxisome proliferator activated receptorγ(PPARg)and tumor necrosis factor(TNF)were searched and obtained in the Protein Data Bank database.The PyMOL 2.3.4 software was used to perform operations such as water removal and ligand removal from receptor proteins,the AutoDockTools software was used to modify 12 receptor proteins such as hydrogenation and balance charge,and the Grid program was used to process each receptor protein.The AutoDock Vina 1.1.2 was used to perform molecular docking of 3 rece

关 键 词：慢性结肠炎 黄芩 白芍 网络药理学 

分 类 号：R285.5[医药卫生—中药学]