广西医学2024，Vol.46Issue(11)：1716-1726,11.DOI:10.11675/j.issn.0253-4304.2024.11.13
基于生物信息学、网络药理学和分子对接方法探讨苦丁茶治疗扩张型心肌病的作用机制
Mechanism of Ilex Kudingcha for the treatment of dilated cardiomyopathy based on bioinformatics,network pharmacology and molecular docking methods:an exploration study
摘要
Abstract
Objective To investigate the mechanism of Ilex Kudingcha for the treatment of dilated cardiomyopathy(DCM)based on bioinformatics,network pharmacology,and molecular docking methods.Methods Active chemical components and their effect targets of Ilex Kudingcha were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the databases such as PubChem,SwissTargetPrediction,and UniProt.Targets related to DCM were obtained from the databases of GeneCards®,OMIM®,and DisGeNET,and the intersection of the aforementioned targets was acquired.The protein-protein interaction(PPI)network of the intersection targets was established for screening the core targets by using the STRING database and Cytoscape software.The components-targets network diagram was established for screening the key active components by employing the Cytoscape software.Through the R language software,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersection targets.The online tool GEO2R of GEO database was used to perform analysis on 3 microarray datasets of GSE1145,GSE42955,and GSE5406 for screening differentially expressed genes.For common genes between differentially expressed genes and core target genes,the receiver operating characteristic(ROC)curve was drawn by the R language software to analyze their predictive efficiency.Molecular docking validation was performed on the key active components and core targets.Results A total of 9 active chemical components and 369 effect targets of Ilex Kudingcha were screened.Targets related to DCM were 1597,and the intersection targets were 105.The key active components of Ilex Kudingcha for treating DCM contained quercetin,kaempferol,β-sitosterol,and pomolic acid,etc.,and the core targets included serine/threonine kinase 1(AKT1),proto-oncogene tyrosine protein kinase(SRC),tumor necrosis factor(TNF),Jun proto-oncogene,AP-1 transcription factor subunit(JUN)etc.The intersection targets were involved in biological processes such as wound healing,epithelial cell proliferation,reproductive system development,and response to oxidative stress,in cellular compositions such as membrane microdomains raft,membrane raft,outer part of plasma membrane,focal adhesion,in molecular functions such as signal receptor activator activity,receptor ligand activity,protein serine/threonine/tyrosine kinase activity,and cytokine receptor binding,as well as in signaling pathways such as lipid and atherosclerosis,PI3K/AKT signaling pathway,AGE/RAGE signaling pathway.AKT1,SRC,TNF,HSP90AA1 and JUN were differentially expressed in 3 GEO datasets of GSE1145,GSE42955 and GSE55406,and these genes had favorably high diagnostic efficiency for DCM.The results of molecular docking revealed that there was favorably high binding activity between the key active component and core targets.Conclusion The main active components of Ilex Kudingcha in terms of quercetin,kaempferol,β-sitosterol,and pomolic acid,etc.,may participate in regulating cellular compositions such as membrane microdomain raft,membrane raft,outer part of plasma membrane,and focal adhesion,in molecular functions such as signal receptor activator activity,receptor ligand activity,cytokine receptor binding,and protein serine/threonine/tyrosine kinase activity,in biological processes in epithelial cell proliferation,response to oxidative stress,as well as in signaling pathways such as lipid and atherosclerosis,PI3K/AKT signaling pathway,AGE/RAGE signaling pathway,so as to exert therapeutic effect of DCM through mainly acting on the core targets such as AKT1,SRC,TNF,HSP90AA1 and JUN.关键词
扩张型心肌病/苦丁茶/生物信息学/网络药理学/分子对接/作用机制Key words
Dilated cardiomyopathy/Ilex Kudingcha/Bioinformatics/Network pharmacology/Molecular docking/Mechanism分类
医药卫生引用本文复制引用
黎承班,高书亚,何斌,权里平,王育博,余林星,刘顺利,刘莉..基于生物信息学、网络药理学和分子对接方法探讨苦丁茶治疗扩张型心肌病的作用机制[J].广西医学,2024,46(11):1716-1726,11.基金项目
国家自然科学基金(82360080) （82360080）
广西自然科学基金(2023GXNSFAA026010) （2023GXNSFAA026010）
