摘要
目的:运用网络药理学及分子对接方法探讨桂枝茯苓丸治疗慢性阻塞性肺疾病急性加重期(Acute Exacerbation of Chronic Obstructive Pulmonary Disease,AECOPD)的有效成分、靶点、网络通路及潜在分子机制.方法:综合利用中药系统药理学数据库与分析平台收集桂枝茯苓丸中各活跃成分及对应靶点,接着运用GeneCard、DrugBank、DisGeNET等数据库进一步确定AECOPD相关靶标.采用Venny在线平台获取药物与疾病靶点的交集,通过STRING数据库搭建蛋白质-蛋白质相互作用网络,利用Cytoscape选出关键靶点.通过DAVID 6.8数据库进行靶点基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析.采用Autodock Vina进行分子对接验证.结果:获得桂枝茯苓丸的43种活性成分,核心活性成分包括槲皮素、山柰酚、β-谷甾醇、黄芩苷和鞣花酸.药物靶点有218个,与AECOPD相关的疾病靶点有980个,二者的交集靶点有114个.通过GO分析获得1 484条生物过程、41条细胞组成和95条分子功能,通过KEGG通路富集分析获得169条信号通路.结论:桂枝茯苓丸中含有槲皮素、山柰酚、β-谷甾醇、黄芩苷和鞣花酸等有效成分,可能通过调节白细胞介素(Interleukin,IL)-6、IL-1B、丝氨酸/苏氨酸蛋白激酶1、基质金属蛋白酶9、肿瘤蛋白p53等蛋白表达治疗AECOPD.其作用机制主要与抑制脂质和动脉粥样硬化、IL-17信号通路、磷脂酰肌醇3激酶/蛋白激酶B信号通路、肿瘤坏死因子信号通路、癌症通路等信号通路有关.
Abstract
Objective:To explore the effective components,targets,network pathways,and potential molecular mechanisms of Guizhi Fuling Wan(桂枝茯苓丸)in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)by network pharmacology and molecular docking methods.Methods:The active components and their corresponding targets of Guizhi Fuling Wan were retrieved by TCMSP,and the AECOPD related targets were further determined by GeneCard,DrugBank,DisGeNET and other databases.The Venny online tool was used to process the intersection targets of drug and disease.The protein-protein interaction network diagram was constructed by STRING database,and key targets were selected by Cytoscape.DAVID 6.8 database was utilized for GO function and KEGG pathway enrichment analyses.Molecular docking verification was conducted by Autodock Vina.Results:Forty-three active components of Guizhi Fuling Wan were obtained,among which core active components included quercetin,kaempferol,β-sitosterol,baicalin,and ellagic acid.There were 218 drug targets,980 disease targets related to AECOPD,and 114 intersection targets of the above two.The GO analysis revealed 1 484 biological processes,41 cellular components,and 95 molecular functions,while KEGG pathway enrichment analysis obtained 169 signaling pathways.Conclusion:Guizhi Fuling Wan contains effective components such as quercetin,kaempferol,β-sitosterol,baicalin,and ellagic acid,which may treat AECOPD by regulating the expressions of proteins such as IL-6,IL-1B,AKT1,MMP9,and TP53.Its action mechanism is primarily associated with the inhibition of lipid and atherosclerosis,IL-17 signaling pathway,PI3K/Akt signaling pathway,TNF signaling pathway,cancer pathway and other signaling pathways.
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