基于网络药理学预测丹参-柴胡药对治疗酒精性肝病的作用机制

doi:10.3976/j.issn.1002-4026.2021.05.003

摘要/Abstract

摘要： 基于网络药理学方法预测丹参-柴胡药对治疗酒精性肝病的作用机制。通过数据库筛选丹参、柴胡的有效活性成分及相应的靶蛋白，并预测和筛选丹参-柴胡药对治疗酒精性肝病的作用靶点。运用Cytoscape 3.7.2软件构建药物-成分-靶点-疾病网络图。绘制关键靶点蛋白质-蛋白质相互作用(protein protein interaction, PPI)网络。采用Metascape数据库对有效作用靶点进行基因本体（gene ontology, GO）注释分析、京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析。筛选出丹参化合物65个，有效靶点162个，柴胡化合物17个，有效靶点251个。通过筛选得到丹参-柴胡药对与酒精性肝病的交集靶点161个。PPI网络发现AKT1、IL6、TP53、VEGFA、TNF、CASP3、EGF等可能是丹参-柴胡药对治疗酒精性肝病的关键靶点。GO注释分析涉及对无机物的反应、对有毒物质的反应、膜筏、枝晶、转录因子结合、蛋白质结构域特异性结合等信号通路。KEGG通路分析涉及肿瘤信号通路、流体剪切应力与动脉粥样硬化、癌症中的蛋白多糖、糖尿病并发症中的AGE-RAGE信号通路等通路。初步探究了丹参-柴胡药对治疗酒精性肝病的关键靶点和涉及的生物学过程及信号通路，发现其作用是多靶点、多通路的。

关键词: 丹参, 柴胡, 酒精性肝病, 网络药理学, 作用机制

Abstract: Based on the network pharmacology method to predict the action mechanism of Salviae Miltiorrhizae Radix Et Rhizoma-Bupleuri Radix on the treatment of alcoholic liver disease. Screen the effective active ingredients of Salviae Miltiorrhizae Radix Et Rhizoma and Bupleuri Radix and the corresponding target proteins through the database, and predict and screen the target of Salviae Miltiorrhizae Radix Et Rhizoma-Bupleuri Radix for the treatment of alcoholic liver disease. Use Cytoscape 3.7.2 software to construct a drug-component-target-disease network diagram. Map the key target protein-protein interaction (PPI) network. Metascape database was used to conduct gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for effective targets. Sixty-five Salviae Miltiorrhizae Radix Et Rhizoma compounds with 162 effective targets and 17 Bupleuri Radix compounds with 251 effective targets were screened. Through screening, 161 intersecting targets of Salviae Miltiorrhizae Radix Et Rhizoma and Bupleuri Radix for alcoholic liver disease were obtained. PPI network analysis revealed that AKT1, IL6, TP53, VEGFA, TNF, CASP3, and EGF may be the key targets of Salviae Miltiorrhizae Radix Et Rhizoma and Bupleuri Radix for the treatment of alcoholic liver disease. GO annotation analysis involved signaling pathways such as reactions to inorganic substances, reactions to toxic substances, membrane rafts, dendrites, transcription factor binding, and protein domain-specific binding. KEGG pathway analysis involved tumor signaling pathways, fluid shear stress and atherosclerosis, proteoglycans in cancer, and AGE-RAGE signaling pathways in diabetic complications. The key targets of Salviae Miltiorrhizae Radix Et Rhizoma and Bupleuri Radix medicine for the treatment of alcoholic liver disease as well as the biological processes and signaling pathways involved were preliminarily explored, and it was found that the effect is multi-target and multi-pathway.

Key words: Salviae Miltiorrhizae Radix Et Rhizoma, Bupleuri Radix, alcoholic liver disease, network pharmacology, mechanism of action

中图分类号:

R285

孙丹丹, 姜婷, 王刚, 胡勇. 基于网络药理学预测丹参-柴胡药对治疗酒精性肝病的作用机制[J]. 山东科学, 2021, 34(5): 16-25.

SUN Dan-dan, JIANG Ting, WANG-Gang, HU Yong. Predicting the mechanism of action of Salviae Miltiorrhizae Radix Et Rhizoma-Bupleuri Radix for the treatment of alcoholic liver disease based on network pharmacology[J]. Shandong Science, 2021, 34(5): 16-25.

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