基于网络药理学探究三七治疗冠心病的潜在作用机制

目的:研究三七治疗冠心病的成分、靶点及通路,探讨其发挥治疗作用的潜在分子机制。方法:基于网络药理学方法,利用中药系统药理学分析平台(TCMSP)检索获取三七的活性成分;利用DRAR-CPI服务器、GeneCards和DisGeNET数据库筛选出与三七治疗冠心病相关的作用靶标;采用Cytoscape3.6.0软件构建三七有效成分-冠心病作用靶标网络;采用String数据库绘制作用靶标的相互作用网络,并运用NetworkAnalyzer工具计算靶标连接度,筛选出潜在核心靶标,然后通过SystemsDockWebSite服务器的分子对接验证核心靶标与有效成分的结合力;利用KEGG通路富集分析和基因本体(GO)分类富集分析获取三七治疗冠心病的重要信号通路和分子功能,并构建重要信号通路的“有效成分-作用靶标-信号通路”网络。结果:筛选出三七中治疗冠心病的5个有效成分(豆甾醇、β-谷固醇、人参皂苷rh2、槲皮素、三七皂苷r1),5个成分共作用于96个靶标并存在134种作用关系;5个核心靶标分别为蛋白激酶B(AKT)、白细胞介素6(IL-6)、血管内皮生长因子A(VEGFA)、c-JUN蛋白(c-JUN)、肝磷脂结合表皮生长因子(HB-EGF),其主要通过改变蛋白结合作用以及调控磷酯酰肌醇3激酶/蛋白激酶B(PI3K/AKT)、低氧诱导因子1(HIF-1)、丝裂原活化蛋白激酶(MAPK)等信号通路来发挥治疗冠心病的作用。结论:三七治疗冠心病不仅是通过作用于多个靶标而发挥多种效果,而且可通过靶标之间的相互作用产生复杂的网络调节效果。

Potential Mechanism of Panax notoginseng for Coronary Heart Disease Based on the Network Pharmacology

OBJECTIVE:To explore the component,target and pathway of Panax notoginseng for coronary heart disease (CHD)and its potential molecular mechanism. METHODS:Based on network pharmacology,active components of P. notoginseng were retrieved with TCMSP platform. The targets of P. notoginseng for CHD were screened by using DRAR-CPI server,GeneCards and DisGeNET databases. Cytoscape 3.6.0 software was used to form the effective components-CHD targets network of P. notoginseng. String database was used to draw target interaction network. Network Analyzer tool was used to calculate target connectivity,and potential core targets were screened. Molecular docking between the core targets and the effective components of P. notoginseng was performed by Systems Dock Web Site server. KEGG pathway enrichment analysis and gene ontology(GO) enrichment analysis were also carried out to explore the important signal pathway and molecular function of P. notoginseng for CHD.“Effective component-target-signal pathway”network of important signal pathway were constructed. RESULTS:Five effective components(stigmasterol,β-sitosterol,ginsenoside rh2,quercetin,notoginsenoside r1)were screened from P. notoginseng for CHD,which acted on 96 targets and had 134 functional relationships. Five core targets were protein kinase B(AKT),interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),c-JUN protein(c-JUN)and heparin binding epidermal growth factor (HB-EGF),which played an important role in the treatment of CHD by altering protein binding and regulating signaling pathways as phosphatidylinositol-3 kinase-protein/kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1)and mitogen-activated protein kinase(MAPK). CONCLUSIONS:P. notoginseng in the treatment of CHD is not only play a variety of effects through the role of multiple targets,but also produce complex network regulation effect through the interaction between targets.