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胃复春片治疗胃癌前病变作用机制的网络药理学研究
Mechanism of Weifuchun Tablets in the Treatment of Precancerous Lesions of Gastric Cancer Based on Network Pharmacology
【摘要】 目的 探讨胃复春片治疗胃癌前病变的作用机制。方法 利用中药系统药理学数据库与分析平台(TCMSP)、Swiss Target Prediction数据库,结合相关文献,收集胃复春片的活性成分和作用靶点,通过检索Genecards,OMIM,DisGeNET和Drugbank数据库收集胃癌前病变相关疾病靶点,取交集后利用Cytoscape软件构建“成分-靶点-疾病”网络,并进行蛋白-蛋白相互作用(PPI)网络构建与分析,筛选得到核心靶点;利用Metascape平台进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,使用Auto Dock Tools和PyMOL软件对核心靶点与中药小分子配体行分子对接。结果 共筛选出活性成分50个,潜在靶点512个,活性成分-疾病靶点208个;成功建立一、二、三级及核心靶点PPI网络,核心靶点为NPM1,HSPA5,HNRNPK,YWHAZ,MCM2,HNRNPA1,PABPC1,ILF3,EEF1A1;GO功能富集分析涉及643个条目,KEGG通路富集分析主要涉及剪接体、乙醇成瘾、细胞周期、前列腺癌、PI3K-Akt信号通路、泛素介导的蛋白水解等相关通路。分子对接结果显示,活性成分与多个核心靶点蛋白结合活性良好。结论 胃复春片可通过chrysosplenol D、hesperetin等活性成分,以NPM1,HSPA5,HNRNPK,YWHAZ,MCM2,HNRNPA1,PABPC1,ILF3,EEF1A1为关键靶点,主要通过剪接体、乙醇成瘾、细胞周期、前列腺癌、PI3K-Akt信号通路、泛素介导的蛋白水解等通路发挥治疗胃癌前病变的作用。
【Abstract】 Objective To investigate the mechanism of Weifuchun Tablets in the treatment of precancerous lesions of gastric cancer(PLGC).MethodsThe active components and action targets of Weifuchun Tablets were collected through the Traditional ChineseMedicine Systems Pharmacology Database and Analysis Platform(TCMSP),Swiss Target Prediction database and relevant literature.The PLGC-related disease targets were screened from GeneCards,Online Mendelian Inheritance in Man(OMIM),DisGeNET andDrugbank databases. After the intersection,the ″ component-target-disease″ network was constructed by Cytoscape software,andprotein-protein interaction(PPI) network was constructed and analyzed to screen the key targets. Metascape platform was used forgene ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally,AutoDock Tools and PyMOL software were used for molecular docking of key targets and small molecule ligands of traditional Chinesemedicine.ResultsFifty active components of Weifuchun Tablets in the treatment of PLGC were obtained,including 512 potential targets and 208 active components-disease targets. The primary,secondary and tertiary PPI networks and PPI network of keytargets have been successfully established,and the key targets were NPM1,HSPA5,HNRNPK,YWHAZ,MCM2,HNRNPA1,PABPC1,ILF3 and EEF1A1. A total of 643 items were analyzed by GO function enrichment analysis,while the spliceosome,alcohol addiction,cell cycle,prostate cancer,PI3K-Akt signaling,ubiquitin-mediated proteolysis and other related pathways were involved in KEGGpathway enrichment analysis. The results of molecular docking showed that the active components had a good binding activity withmultiple key target proteins.ConclusionThe mechanism of Weifuchun Tablets in the treatment of PLGC through chrysosplenolD,Hesperetin and other active components with NPM1,HSPA5,HNRNPK,YWHAZ,MCM2,HNRNPA1,PABPC1,ILF3,EEF1A1 as thekey targets,and with spliceosome,ethanol addiction,cell cycle,prostate cancer,PI3K-Akt signaling,ubiquitin-mediated proteolysispathways as the signaling pathway.
【Key words】 Weifuchun Tablets; precancerous lesions of gastric cancer; network pharmacology; molecular docking; mechanism;
- 【文献出处】 中国药业 ,China Pharmaceuticals , 编辑部邮箱 ,2022年14期
- 【分类号】R285
- 【下载频次】215