基于网络药理学和分子对接技术探讨八珍汤治疗大肠癌的作用机制

The action mechanism of the Bazhen decoction on colorectal cancer based on network pharmacology and molecular docking technology

目的:运用网络药理学和分子对接技术预测八珍汤治疗大肠癌(Colorectal Cancer,CRC)的主要活性成分和作用的关键靶点,探讨可能的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)及SwissTargetPrediction筛选预测八珍汤的活性成分及相关作用靶点,利用OMIM、TTD、GeneCards和Drugbank数据库查筛CRC主要作用靶点。利用VennDiagram软件得到八珍汤与CRC的共同靶点。使用Cytoscape 3.9.1构建“药材-活性成分-靶点-疾病”网络、运用STRING构建蛋白质-蛋白质相互作用网络。利用Metascape及R软件对关键靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析。使用PDB、PubChem数据库,以及PyMOL、Chem3D及AutoDock vina软件对主要活性成分及关键靶点进行分子对接验证。结果:八珍汤的129个活性成分通过调控154个CRC相关靶点,尤其是33个核心靶点,参与调控细胞周期进程、增殖和凋亡、信号传导、细胞迁移及血管生成等生物过程,干预丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinases,PI3K)-蛋白激酶B(Akt)等信号通路起到治疗CRC的作用。分子对接验证了5种化合物与关键靶点具有较强的亲和力。结论:八珍汤治疗CRC具有多成分、多靶点、多途径的特点,文章可以为其进一步基础研究及临床应用提供方向和依据。

Objective:The main active components and key targets of the Bazhen decoction(八珍汤)on CRC were predicted by network pharmacology and molecular docking technology,and the possible action mechanism was discussed.Methods:Main chemical components and targets of the Bazhen decoction were screened by TCMSP and SwissTargetPrediction.Main targets of CRC were selected from databases of Online Mendelian Inheritance in Man,Therapeutic Target Database,GeneCards and Drugbank.The common targets of the Bazhen decoction and CRC were obtained by VennDiagram software.Cytoscape 3.9.1 was used to construct a medicinecomponent-target-disease network.A PPI network was constructed by STRING.Metascape platform and R language software was used to perform the GO function enrichment analysis and KEGG pathway enrichment analysis.PDB and PubChem databases,and PyMOL,Chem3D and AutoDock vina software were used to perform the molecular docking verification of key targets and corresponding active ingredients.Results:A total of 129 active components of the Bazhen decoction played a role in the treatment of CRC by regulating 154 related targets,especially 33 core targets,participating in the regulation of biological processes such as cell cycle process,proliferation and apoptosis,signal transduction,cell migration and angiogenesis,and intervening in MAPK,PI3K-Akt and other signal pathways.The molecular docking verified that 5 compounds had strong affinity with key targets.Conclusion:The Bazhen decoction on CRC has the characteristics of multi-component,multi-target and multi-pathway,which can provide the basis and direction for the further basic research and clinical application.