基于网络药理学探讨柴胡抗酒精性肝病的作用机制

Network pharmacology-based exploration of the mechanism of Chinese thorowax root against alcoholic liver disease

目的运用网络药理学的方法研究中药柴胡抗酒精性肝病(ALD)的分子作用机制。方法借助中药系统药理学数据库与分析平台(TCMSP)、Uniprot数据库获取柴胡的成分和作用靶点;结合GeneCrads、OMIM数据库获取并筛选柴胡治疗ALD的靶点;运用Cytoscape 3.9.1软件对柴胡活性成分-作用靶点进行可视化;通过STRING数据库构建蛋白相互作用网络(PPI);运用Metascape平台对交集基因靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果筛选得到12个柴胡活性成分,槲皮素、豆甾醇、山柰酚可能是重要活性成分。涉及治疗ALD的作用靶点111个。具体过程涉及188条信号通路、1582个生物过程、79个细胞组分、139个分子功能富集等多层次功能,其中富集通路主要涉及癌症通路、脂质和动脉粥样硬化、流体剪切应力和动脉粥样硬化、白介素17信号通路等。结论本研究初步研究了柴胡抗ALD的分子机制,体现了柴胡多成分-多靶点-多通路的作用特点,为其进一步研究提供理论依据。

Objective To explore the molecular mechanism of Chinese thorowax root against alcoholic liver disease(ALD)using the network pharmacology method.Methods The components and action targets of Chinese thorowax root were obtained with the help of traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and Uniprot database,and the targets of Chinese thorowax root for the treatment of ALD were obtained and screened using GeneCrads and online Mendelian inheritance in man(OMIM)database.The active components-action targets of Chinese thorowax root were visualized using Cytoscape 3.9.1 software,and a proteinprotein interaction(PPI)network was constructed by STRING database.In addition,the intersection gene targets were subjected to gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)-based enrichment analyses using the Metascape platform.Results 12 active components of Chinese thorowax root were screened,of which quercetin,stigmasterol and kaempferol may be important active components.There were 111 action targets involved in the treatment of ALD.The specific processes involved 188 signaling pathways,1582 biological processes,79 cellular components,139 molecular functions enrichment and other multi-level functions,among which the enrichment pathways mainly involved cancer pathway,lipid and atherosclerosis,fluid shear stress and atherosclerosis,interleukin-17(IL-17)signaling pathway,etc.Conclusion This study has preliminarily explored the molecular mechanism of Chinese thorowax root against ALD,which reflects the multi-component,multi-target,and multi-pathway action characteristics,providing a theoretical basis for its further study.