基于网络药理学与分子对接探讨三七治疗胃癌的作用机制及药效活性物质

To Explore the Mechanism of Action and Active Substances of Panax Notoginseng in the Treatment of Gastric Cancer Based on Net work Pharmacology and Mol ecular Docking

目的:通过网络药理学和分子对接技术探讨中药八宝丹中唯一已知植物成分三七治疗胃癌的潜在药效活性成分及其作用机制。方法:通过TCMSP等数据库筛选三七的有效活性成分及相关靶点蛋白,将GeneCards和DisGeNET等数据库挖掘的胃癌相关靶点和药物靶点蛋白交集;采用Cytoscape3.7.0对药效成分进行分析,建立有效的成分靶点疾病的关系模型。运用STRING数据库构建交集靶点的PPI蛋白互作图。运用David数据库进行KEGG通路和GO分类的富集分析;利用AutoDock Tools 1.5.6软件对三七关键活性成分和核心靶点进行分子对接验证,运用PyMol 2.5软件绘制对接模式图。结果:筛选出三七的有效活性成分99个,映射273个药靶基因。经GeneCards数据库搜集得到胃癌疾病基因15118个,三七与胃.癌的交集靶点234个,分析得到165条KEGG富集通路.195条GO功能富集条目,主要包括癌症的途径、PI3K-Akt通路、MAPK通路.Ras通路,以及RNA聚合酶启动子转录的正向调节、信号转导、基因表达的正调控、正调节细胞增殖、负调节细胞凋亡等生物过程;其中高Hub值的化合物成分豆甾醇、人参皂苷rh2与胃癌基因白细胞介素-6(interleukin-6,IL-6)、TP53、肿瘤坏死因子(tumor necrosis factor,TNF)存在较强的分子对接关系。结论:三七治疗胃癌的机制涉及多成分多靶点和多途径,三七可能是通过调节癌症的途径、PI3K/Akt通路、MAPK通路、Ras信号通路等在胃癌治疗中发挥作用,其中豆甾醇、人参皂苷rh2可能是三七药效的关键活性成分之一。

Objective:Through net work pharmacology and molecular docking technolo-gy,the only known plant component of Babaodan in the treatment of gastric cancer potential active ingredients and its mechanism of action.Methods:The active ingredients and related target proteins of Panax Notoginseng were screened by TCMSP and other databases,and the gastric cancer related targets and drug target proteins mined by GeneCards and DisGeNET databases were int ersected.Cytoscape3.7.0 was used to analyze pharmacody namic compo-nents to establish an effective component-target-disease relationship model.The PPI protein interaction map of intersecting targets was constructed by using String database.The enrich-ment analysis of KEGG pathway and GO classification was carried out using David data-base.AutoDock Tools 1.5.6 sof tware was used to verify the molecular docking of key active ingredients and core targets of Panax Notoginseng,and PyMol 2.5 software was used to draw the docking model diagram.Results:99 active ingredients of Panax Notoginseng were selected and 273 target genes were mapped.Through GeneCards database,15118 gastric cancer disease genes and 234 intersection targets of Notochi and gastric cancer were collect-ed,and 165 KEGG enrichment pathways and 195 GO functional enrichment items were ob-tained,mainly including cancer pathway,PI3K-Akt pathway,MAPK pathway and Ras path-way.And RNA polymerase promoter transcription positive regulation,signal transduction,gene expression positive regulation,positive regulation of cell prolifera tion,negative regula-tion of cell apoptosis and other biological processes;Among them,stigasterol and ginsen-oside rh2 with high Hub value had strong molecular docking relationship with gastric cancer genes IL-6,TP53 and TNF.Conclusion:Panax Notoginseng may play a role in the treatment of gastric cancer through regu lating cancer pathways,PI3K/Akt pathway,MAPK pathway and Ras signaling pathway,among which stigmosterol and ginsenoside rh2 may be one of the key active ingredients of Panax notoginseng.