基于网络药理学及分子对接研究黄连温胆汤治疗Z综合征作用机制

Research on the Mechanism of Huanglian Wendan Decoction in the Treatment of Z Syndrome Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接方法探讨黄连温胆汤治疗Z综合征的可能作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)及中药成分数据库(TCMID)筛选并收集黄连温胆汤的活性成分及其对应靶标。利用Uniprot数据库获取药物活性成分对应靶标的基因,并与通过人类基因组注释数据库(GeneCards)和《人类孟德尔遗传》数据库(OMIM)所获得的人Z综合征(OSAS合并MS)相关基因进行比较,获得黄连温胆汤与Z综合征重合的潜在作用靶标基因。使用Cytoscape3.7.2软件绘制黄连温胆汤的“疾病-药物-成分-靶标-通路”网络图。通过String数据库获取潜在作用靶标之间的相互作用数据表,然后导入Cytoscape3.7.2软件构建靶蛋白质相互作用网络图。然后基于bioconductor提供的人类基因注释数据库org.Hs.eg.db,利用R语言的clusterfiler程序包对黄连温胆汤治疗Z综合征的潜在作用靶标进行GO分类富集分析和KEGG通路富集分析。结果:得到黄连温胆汤治疗Z综合征有134个候选活性成分,包括木犀草素、槲皮素、黄芩素、小檗碱、黄芩苷等;65个潜在作用靶标,包括AKT1、IL6、VEGFA和MMP-9等;116条通路,包括MAPK,核因子-κB,PI3K-Akt,Toll样受体等信号通路。分子对接表明,木犀草素、槲皮素、黄芩素可与3个关键候选靶蛋白(IL-6、AKT1、MMP-9)有较好的结合性。结论:黄连温胆汤可能通过作用于IL6、VEGFA和MMP-9等靶标及MAPK,核因子-κB,PI3K-Akt,Toll样受体等信号通路干预Z综合征的发生发展。

Objective:To explore the possible mechanism of Huanglian Wendan Decoction in the treatment of Z syndrome based on network pharmacology and molecular docking.Methods:The active components and their corresponding targets of Huanglian Wendan Decoction were screened and collected on TCMSP and TCMID.Using UniProt database to obtain the target genes of the active components of drugs.Compared with the genes of human Z syndrome(OSAS combined with MS)obtained from the Genecards and OMIM databases,the potential target genes of Huanglian Wendan Decoction overlapped with Z syndrome were obtained.The network diagram of“disease-drug-component-target-pathway”of Huanglian Wendan Decoction was drawn by using the software of Cytoscape 3.7.2.The interaction data table between potential targets was obtained through string database,and then the interaction network diagram of target proteins was constructed by importing the software of Cytoscape 3.7.2.Then,based on the human gene annotation database org.Hs.eg.db provided by Bioconductor,the cluster filer package of R language was used to analyze the potential target of Huanglian Wendan Decoction in the treatment of Z syndrome by going classification enrichment analysis and KEGG pathway enrichment analysis.Results:There were 134 candidate active components,including luteolin,quercetin,scutellarin,baicalin,etc.;65 potential targets,including AKT1,IL6,VEGFA and MMP-9;116 pathways,including MAPK,NF kappa B,PI3K Akt,toll-like receptor and other signal pathways.Molecular docking showed that luteolin,quercetin and baicalein could bind to 3 key candidate target proteins(IL-6,AKT1 and MMP-9).Conclusion:Based on the network pharmacology method and molecular docking,the therapeutic target and signal pathway of Huanglian Wendan Decoction in the treatment of Z syndrome are excavated,which provides a new research method for the study of the mechanism of Huanglian Wendan Decoction in the treatment of OSAS,and also provides a new idea for the further study of the mechanism of treating different diseases with the same therapeutic principle in traditional Chinese medicine.