基于网络药理学和分子对接技术探讨功劳叶、仙鹤草药对治疗缺血性中风的作用机制

A network pharmacology and molecule docking approach to investigating active compounds and mechanisms of gonglaoye-xianhecao herbal pair for ischemic stroke

目的应用网络药理学方法探讨功劳叶、仙鹤草药对治疗缺血性中风的作用机制。方法通过TCMSP平台和文献获取功劳叶、仙鹤草药对主要化学成分,通过PharmMapper预测靶点。从Drugbank、Disgenet、TTD、Genecards、OMIM数据库收集疾病靶点,使用Cytoscape 3.7.1软件构建成分-靶点相互作用网络,进而拓扑学分析得到核心活性成分;使用STRING数据库绘制蛋白-蛋白互作网络,进而拓扑学分析得到核心靶点;对交集靶点进行GO功能和KEGG通路富集分析。最后,对核心蛋白和核心化合物进行分子对接。结果筛选出功劳叶、仙鹤草药对治疗缺血性中风的17个有效成分和296个潜在作用靶点。GO富集主要集中在对氧化合物的反应等条目。KEGG主要涉及PI3K-Akt等信号通路。分子对接显示化合物和靶点间具有高亲和力。结论功劳叶、仙鹤草药对治疗缺血性中风具有多靶点、多通路相互作用的机制,为未来实验研究和新药研发提供基础思路。

Aim To clarify the mechanism of Gonglaoye and Xianhecao herbal pair in the treatment of ischemic stroke so as to obtain the substantive evidence using network pharmacology data mining and molecular docking.Methods The main compounds of traditional Chinese medicine were obtained by TCMSP platform and consulting literature,the drug action targets were obtained by TCMSP,and the known genes about ischemic stroke were collected by searching Drugbank,Disgenet,TTD,Genecards,OMIM database,thus the drug-compound-target network map was constructed,and the common target proteins and main compounds were screened.The visual protein-protein interaction network map(PPI)was constructed by string.With the help of Cytoscape software,the original target network of active components was constructed and analyzed,and the gene ontology GO and Jingdu gene and genome encyclopedia KEGG analysis were carried out to analyze the GO function and KEGG pathway enrichment of the common targets of drugs and diseases.Finally,the molecular docking of the core protein and the core compound was carried out according to the relevant node parameters of the compound and protein.Results Seventeen active components and 296 potential targets of Gonglao leaf and crane herbs in the treatment of ischemic stroke were screened.GO enrichment was mainly concentrated in the response to oxides,cell response to chemical stimulation,positive regulation of cell metabolism,constant effect,active regulation of stimulus response,cell communication and so on.KEGG was mainly involved in signaling pathways such as PI3K-Akt,Ras,neuron ligand receptor interaction and so on.Molecular docking showed that quercetin and other active components had high affinity and tight connection with core targets such as AKT1.Conclusions The treatment of ischemic strokec is mainly through the mechanism of ursolic acid,hyperin and other active components,AKT1,cMAPK3 and other multi-targets,PI3K-AKT and other multi-pathway interaction mechanisms.Through this study the theoretical support can be provided for the further clinical application of Gonglaye and crane herbs,providing basic ideas for future experimental research and new drug research and development.