基于网络药理学和分子对接的养心氏片治疗冠心病合并抑郁症机制

Potential Mechanism of Yangxinshi Tablet in Treating Coronary Heart Disease with Major Depressive Disorder Based on Network Pharmacology and Molecular Docking

通过网络药理学和分子对接技术探讨养心氏片(Yangxinshi,YXS)治疗冠心病(coronary heart disease,CHD)合并抑郁症(major depressive disorder,MDD)的机制。使用TCMSP和TCM-ID数据库筛选YXS中的活性化合物及其相关靶点,并在Uniport数据库中获取靶点的标准基因名;通过使用GeneCards和OMIM数据库,收集与冠心病(CHD)和抑郁症(MDD)相关的疾病靶点,对药物靶点和疾病靶点进行交集分析,以获得蛋白质互作关系;利用David数据库进行基因本体(GO)和京都基因与基因百科全书信号通路富集分析(KEGG);最后使用AutodockTools软件进行分子对接验证。富集分析显示YXS中的295个活性成分(如槲皮素、木犀草素、山柰酚和豆甾醇)作用于STAT3、IL1B、IL6等290个靶点。此外,YXS还涉及AGE-RAGE信号通路、脂质与动脉粥样硬化信号通路、流体剪切应力与动脉粥样硬化信号通路等。分子对接结果显示良好的对接效果。YXS治疗CHD合并MDD的药理作用主要通过作用于槲皮素、木犀草素、山柰酚和豆甾醇等活性成分的STAT3、IL1B、IL6等靶点,通过AGE-RAGE、脂质与动脉粥样硬化等信号通路抑制炎症反应,提高5-羟色胺(5-HT)含量等。研究结果为后续的实验研究和临床应用提供了理论基础。

To explore the mechanism of Yangxinshi Tablet(YXS) in the treatment of coronary heart disease(CHD) complicated with major depressive disorder(MDD) by network pharmacology and molecular docking technology.TCMSP and TCM-ID databases were used to screen the active components and related targets of YXS,and Uniport database was used to retrieve the standard gene names of targets.GeneCards and OMIM databases were used to collect the disease targets of CHD and MDD.The drug and disease intersection targets were imported into STRING platform to obtain protein interactions,gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis were performed using David database.AutodockTools software was used for molecular docking verification.Enrichment analysis shows that YXS acts on signal transducer and activator of transcription-3,interleukin 1-β,interleukin-6 and other 290 targets through 295 active components such as quercetin,luteolin,kaempferol and soya-lecithin,involving AGE-RAGE,lipid and atherosclerosis,fluid shear stress and atherosclerosis and other signaling pathways.Molecular docking shows good docking.YXS intervenes in CHD complicated with MDD through multi-components,multi-targets and multi-pathways,providing a theoretical basis for subsequent experimental research and clinical drug use.