The Mechanism of Huanglian and Chuanxiong in the Treatment of Coronary Atherosclerosis and Acute Myocardial Infarction Based on Network Pharmacology

WEI Kangkang; LIU Min; ZHAO Xiaohan; MA Xiaojuan; SHI Dazhuo; CHEN Keji

doi:10.12102/j.issn.1672-1349.2023.23.002

Abstract：Objective:To investigate the difference of the mechanisms of Huanglian and Chuanxiong in the treatment of coronary atherosclerosis(CAS)and acute myocardial infarction(AMI)based on a network pharmacology approach and molecular docking technology.Methods:The differential genes of CAS and AMI were obtained through the comprehensive gene expression database(GEO).The main active ingredients and predicted targets in Huanglian and Chuanxiong were collected from the traditional Chinese medicine systematic pharmacology database and analysis platform(TCMSP).According to drug action targets,protein-protein interaction network diagram(PPI)was constructed and topological analysis was performed.David database was used for gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Schrodinger software was used to dock the key active ingredients of traditional Chinese medicine with the key proteins of CAS and AMI respectively.Results:The active ingredients of Huanglian and Chuanxiong in the treatment of CAS and AMI were similar.PPI network topology analysis showed that there were 17 target proteins for the treatment of CAS and 37 target proteins for the treatment of AMI,with a total of 16 identical target proteins,while AMI had 21 more specific target proteins,Huanglian and Chuanxiong could further act on new targets on the basis of regulating CAS related targets in AMI.GO enrichment analysis showed that blood activating and detoxifying herbs interfered with CAS and AMI through different biological processes.KEGG enrichment analysis showed that there were 22 CAS-related pathways and 90 AMI-related pathways,and there were 17 common pathways between CAS and AMI,but there were differences in the enrichment degree between CAS and AMI.There were 73 specific pathways of AMI,mainly tumor necrosis factor(TNF)signaling pathway,nuclear transcription factor-κB(NF-κB)signaling pathway,etc.,involving multiple inflammatory pathways.These results indicated that Huanglian and Chuanxiong could further regulate the specific pathway of AMI on the basis of the regulation of CAS related pathway.Molecular docking results showed that the main compounds and targets were well combined,supporting the network pharmacological results.Conclusion:In this study,the possible mechanism of action of Huanglian and Chuanxiong in the treatment of CAS and AMI based on multi-compound,multi-target and multi-pathway were explained.It was found that Chinese herbs could further act on the specific proteins and pathways in the occurrence of AMI on the basis of regulating the common targets and pathways of CAS.The different mechanisms of activating blood and detoxification therapy in different stages of coronary heart disease were revealed,and the theory of"stasis poison"of coronary heart disease was perfected from the pharmacological level.