基于网络药理学及分子对接探讨桑叶-菊花治疗高血压的作用机制

Study on the mechanism of action of Folium Mori-Flos Chrysanthemi on hypertension based on network pharmacology and molecular docking

本文旨在通过网络药理学和分子对接方法探讨桑叶-菊花治疗高血压的潜在分子作用机制。首先从GEO数据库下载基因芯片数据,使用R语言limma包筛选差异表达基因,通过中药系统药理学分析平台筛选桑叶-菊花有效成分及相应靶蛋白,利用Venn软件取药物与疾病交集靶点,运用Cytoscape3.7.2软件构建“化合物-靶点”网络及可视化分析,并用Bisogenet和CytoNCA插件对关键靶点进行蛋白网络互作及拓扑分析,通过David数据库和R语言clusterProfiler包对关键靶点进行GO功能富集及KEGG通路分析,应用AutoDock Vina软件对活性成分与关键靶点进行结果验证。结果显示桑叶-菊花成分作用于高血压的靶点41个,拓扑分析出156个核心靶点信息,GO分析共包含52条生物过程、13条分子功能、15条细胞组成等80条富集结果,KEGG通路分析发现39个条目,涉及IL-17信号通路、流体剪切应力与动脉粥样硬化信号通路、TNF信号通路等。分子对接结果显示与关键靶点对接较好的成分有槲皮素、木犀草素。本研究初步揭示了桑叶-菊花通过“多成分-多靶点-多途径”协同作用发挥降压作用,为深入研究其物质基础及作用机制奠定了基础。

This study aims to explore the potential molecular mechanism of Folium Mori-Flos Chrysanthemi(FM-FC)on the treatment of hypertension by network pharmacology and molecular docking methods.Firstly,the gene chip data was downloaded from GEO database,differentially expressed genes were screened with R language limma package,the effective components and corresponding target proteins of FM-FC were screened from Traditional Chinese Medicine System Pharmacology Database(TCMSP),the intersection targets of drugs and diseases were extracted with Venn software,the construction of"compound-target"network and visual analysis were completed by Cytoscape3.7.2 software,the protein network interaction and topology analysis of key targets were performed by Bisogenet and CytoNCA plug-ins.Then,David database and R language clusterProfiler package were used for GO function enrichment and KEGG pathway analysis of key targets.Finally,the results of active components and key targets were verified by AutoDock Vina software.The results showed that FM-FC acted on 41 targets of hypertension,156 core target information was revealed by topological analysis.A total of 80 enrichment results including 52 biological processes,13 molecular functions and 15 cell composition were obtained through GO analysis.KEGG pathway analysis found 39 items,involving IL-17 signal pathway,fluid shear stress and atherosclerosis signal pathway,TNF signal pathway,etc.The molecular docking results showed that quercetin and luteolin were components that docked well with key targets.We have revealed preliminarily that FM-FC exerts a hypotensive effect through the synergistic effect of"multi-component-multi-target-multi-pathway"in this study,which will lay a foundation for further study of its material basis and mechanism of action.