藏族药矮紫堇抗急性心肌缺血的网络药理学研究

Network pharmacology study of Tibetan medicine Corydalis Herba against acute myocardial ischemia

通过SciFinder及CNKI数据库完成化合物搜索,并在FAFdurgs4、SEA Search Server数据库进行类药性筛选,结合在OMIM、GeneCards、DurgBank等疾病靶点数据库中搜索到的急性心肌缺血相关靶点集,并借助Cytoscape软件建立“化学成分-靶点-通路-疾病”网络,预测矮紫堇抗急性心肌缺血的潜在活性成分。通过STRING数据库构建蛋白互作(PPI)网络并预测网络中的核心靶点,利用DAVID数据库、R软件对核心靶点进行富集分析,最后利用Autodock Vina等软件将网络中预测到的潜在活性成分与核心靶点进行分子对接验证。结果显示,矮紫堇与急性心肌缺血相关的化合物共60个,涉及73个潜在的靶点,GO功能富集分析得到282条生物学过程(BP)、49条细胞成分(CC)、78条分子功能(MF);KEGG富集到85条通路,涉及酒精中毒通路、内分泌抵抗通路、钙离子信号通路、cAMP信号通路、血管内皮生长因子信号通路及心肌细胞的肾上腺素能信号转导通路等。网络拓扑分析结果表明,矮紫堇抗急性心肌缺血的关键成分可能为四氢巴马汀、四氢非洲防己碱、N-反式-阿魏酰去甲辛弗林、N-顺式-对香豆酰去甲辛弗林、N-反式-对香豆酰去甲肾上腺素、N-反式-对香豆酰去甲辛弗林,核心靶点包括CDH23、SCN4B、NFASC。分子对接结果显示,矮紫堇的关键成分与核心靶点具有稳定的结合活性。该研究为进一步阐明矮紫堇抗急性心肌缺血的药效物质、后续的临床应用及开发提供了一定的参考。

In this study,the compound search was completed through SciFinder and CNKI databases,and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases.In addition,based on the target sets related to acute myocardial ischemia(AMI)searched in disease target databases such as OMIM database,GeneCards database and DrugBank,a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba,a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C.mucronifera against AMI.A protein-protein interaction(PPI)network was constructed through the STRING database and the core targets in the network were predicted.And the enrichment analyses of core targets were completed by DAVID database and R software.Furthermore,a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina.The present results showed that there were 60 compounds related to AMI in Corydalis Herba,involving 73 potential targets.The GO functional enrichment analysis obtained 282 biological processes(BP),49 cell components(CC)and 78 molecular functions(MF).KEGG was enriched into 85 pathways,including alcoholism pathway,endocrine resistance pathway,calcium signaling pathway,cAMP signaling pathway,vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells.The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine,etrahydrocolumbamine,N-trans-feruloyloctopamine,N-cis-p-coumaroyloctopamine,N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine,and their core targets might be CDH23,SCN4 B and NFASC.The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets.This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI,subsequent clinical application,and development.