基于“肝藏血”理论运用网络药理学探究地五养肝胶囊抗肝硬化血小板减少的活性成分与生物学基础

Exploring the active components and biological basis of Diwu Yanggan capsule against thrombocytopenia in liver cirrhosis with network pharmacology based on the theory of "liver storing blood"

目的:基于中医“肝藏血”理论运用网络药理学初步探究地五养肝胶囊抗肝硬化血小板减少的潜在活性成分与生物学基础。方法:利用TCMSP、PharmMapper数据库查阅相关文献,共同检索地五养肝胶囊胶囊活性成分及对应靶点,通过GeneCards、NCBI和DisGeNET数据库及相关文献检索肝硬化血小板减少症相关作用的靶点,利用STRING数据库构建地五养肝胶囊抗肝硬化血小板减少潜在的作用蛋白的相互作用网络。利用R语言的clusterProfiler软件包对地五养肝胶囊抗肝硬化血小板减少潜在靶点进行基因本体(GO)富集分析和京都基因及基因组百科全书(KEGG)富集通路分析,并构建出药物与疾病映射靶基因及通路网络。结果:筛选出地五养肝胶囊抗肝硬化血小板减少的活性成分120个,包括槲皮素、异甘草苷、甘草次酸、绿原酸、五味子乙素、去甲氧基姜黄素等;潜在作用蛋白47个,包括TP53、Alb、TNF、IL6等。GO分析总共富集到1 551条生物过程(BP)相关,37项细胞组成相关和195项分子功能相关。KEGG富集通路分析共富集到151条信号通路。地五养肝胶囊“肝生血”抗肝硬化血小板减少主要涉及调控铁死亡相关信号通路、MAPK信号通路、IL-17信号通路、HIF-1信号通路等信号通路。结论:地五养肝胶囊可能通过以槲皮素、异甘草苷、甘草次酸、绿原酸、五味子乙素等生物活性成分调控TP53信号通路的铁死亡抗肝硬化血小板减少。

Objective:To explore the potential active components and biological basis of Diwu Yanggan(DWYG)capsule against thrombocytopenia in liver cirrhosis by network pharmacology based on the theory of"liver storing blood"in traditional Chinese medicine.Methods:The active components and corresponding targets of DWYG were retrieved by TCMSP,PharmaMapper databases and related literature,and the targets related to thrombocytopenia in cirrhosis were retrieved by GeneCards,NCBI,DisGeNET databases and related literature.The potential protein interaction(PPI)network of DWYG against thrombocytopenia in cirrhosis was constructed by STRING database.The R package clusterProfiler was used to conduct gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)enrichment pathway analysis of DWYG potential targets for anti liver cirrhosis thrombocytopenia,and further build a drug and disease mapping target genes and pathway networks.Results:120 active components of DWYG were screened,including quercetin,isoliquiritin,18β-Glycyrrhetic acid,chlorogenic acid,schisandrin B,demethoxycurcumin,etc;There are 47 potential proteins,including TP53,ALB,TNF,IL6,etc.In GO analysis,1551 biological processes(BP),37 cell compositions(CC)and 195 molecular functions(MF)were enriched.The KEGG enrichment pathway analysis enriched 151 signal pathways.The anti liver cirrhosis thrombocytopenia related iron death of DWYG mainly involves in regulating iron death related signal pathway,MAPK signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway and other signaling pathways.Conclusion:The anti liver cirrhosis thrombocytopenia effect of DWYG may due to the regulation of TP53 signal pathway related iron death through quercetin,isoliquiritigenin,glycyrrhetinic acid,chlorogenic acid,schisandrin B and other bioactive components.