基于网络药理学和分子对接技术探究丹参-红景天抗心肌缺血的作用机制

To explore the therapeutic mechanism of Salvia miltiorrhiza and Rhodiola rosea on myocardial ischemia based on network pharmacology and molecular docking technology

目的基于网络药理学和分子对接技术研究丹参-红景天药对治疗心肌缺血(MI,myocardial ischemia)的潜在机制。方法初步基于中药系统药理分析平台TCMSP和文献筛选丹参和红景天活性成分,自GeneCards及其他数据库可以确定MI的靶点。之后,选择活性成分相应靶点以及疾病靶点之间的交集位置。另外,引入STRING数据库分析各个靶点彼此之间的影响,使用R软件中的Cluster Profiler包分析生物功能和信号通路富集。基于Cytoscape应用建立起蛋白质-蛋白质关联性以及组分靶链路体系,确定主要的活性物质以及靶点。Vina软件用于将核心靶蛋白与药物活性成分对接。结果筛选共得到342个药物潜在靶点,2241个MI潜在靶点,201个共有靶点;GO富集分析得到3276条(P<0.05);KEGG富集分析得到188个(P<0.05);分子对接结果表明靶蛋白与药物活性成分结合较密切。结论丹参-红景天药对可能作用于STAT3、JUN、AKT1和MAPK3等调节炎症、细胞凋亡和增殖做为治疗MI的分子机制,反映出中药对MI治疗通过多靶点和多途径的特点,为进一步揭示其药理基础提供新思路。

Objective To investigate the potential mechanism of salvia miltiorrhist-Rhodiola in the treatment of myocardial ischemia(MI)based on network pharmacology and molecular docking techniques.Methods The active components of salvia miltiorrhiza and Rhodiola rosea were screened based on TCMSP and literature.The target of MI could be determined from GeneCards and other databases.After that,the intersection location between the corresponding target of the active ingredient and the disease target is selected.In addition,the STRING database was introduced to analyze the influence of each target on each other,and the Cluster Profiler package in R software was used to analyze biological functions and signal path enrichment.Based on the Cytoscape application,the protein-protein correlation and component target link system are established to determine the main active substances and targets.Vina software is used to interface core target proteins with drug-active ingredients.Results A total of 342 potential drug targets,2241 potential MI targets and 201 common targets were obtained.GO enrichment analysis yielded 3276(P<0.05)samples.By KEGG enrichment analysis,188 samples were obtained(P<0.05).The results of molecular docking showed that the target protein was closely bound to the active ingredient.Conclusion Salviorrhiza-Rhodiola pair may act on STAT3,JUN,AKT1 and MAPK3 to regulate inflammation,apoptosis and proliferation as the molecular mechanism of MI treatment,which reflects the characteristics of Chinese medicine treating MI through multi-target and multi-pathway,and provides new ideas for further revealing its pharmacological basis.