基于网络药理学和分子对接技术探讨化橘红治疗酒精性肝损伤的潜在作用机制

Potential mechanism of Citri Grandis Exocarpium on alcoholic liver injury based on network pharmacology and molecular docking technology

目的利用网络药理学和分子对接技术研究化橘红抗酒精性肝损伤的潜在分子作用机制。方法在中药系统药理学数据库与分析平台(TCMSP)中获取化橘红的有效成分以及成分靶点,使用GeneCards、OMIM、TTD和DisGenet数据库获取疾病靶点基因信息,借助韦恩图选取活性成分靶点以及疾病靶点基因的交集获取化橘红治疗酒精性肝损伤的潜在作用靶点;利用STRING数据库构建蛋白相互作用网络(PPI),并采用Cytoscape软件得到核心靶点网络图;最后使用Metascape数据库对核心靶点进行基因本体论(GO)功能富集和基因百科全书(KEGG)分析,利用AutoDock Tools进行活性成分与核心靶点的分子对接验证。结果得到10个有效成分、98个成分靶点基因和1531个疾病靶点基因,两者取交集后获取67个交集靶点。利用STRING数据库和Cytoscape软件最终得到肿瘤蛋白p53(TP53)、前列腺素内过氧化物酶2(PTGS2)、半胱氨酸蛋白酶3(CASP3)、转录因子AP-1(JUN)、蛋白激酶B1(AKT1)5个核心靶点。GO分析和KEGG分析分别获得过氧化物酶体等50条目和脂质、动脉粥样硬化等20条信号通路。结论化橘红可通过多个成分作用于多个靶点发挥抗炎、抑制细胞凋亡等作用,进而抑制酒精性肝损伤。

Objective To investigate the potential molecular mechanisms of Citri Grandis Exocarpium in treatment of alcoholic liver injury by network pharmacology and molecular docking.Methods The active components and component targets of Citri Grandis Exocarpium were obtained from the TCMSP,and the gene information of disease target was obtained from GeneCards,OMIM,TTD,and DisGenet databases.The potential targets of Citri Grandis Exocarpium in treatment of alcoholic liver injury were obtained by the intersection of active component targets and disease targets selected by Venn diagram.The protein interaction network(PPI)was constructed using STRING database,and Cytoscape software was used to obtain the core target network map.Finally,Metascape database was used for gene ontology(GO)functional enrichment and Gene Encyclopedia(KEGG)analysis of the core target,and AutoDock Tools was used to verify the molecular docking between the active ingredients and the core targets.Results 10 active components,98 component target genes,and 1531 disease target genes were obtained.67 intersection targets were obtained after the intersection of the two genes.Five core targets including p53(TP53),prostaglandin peroxidase 2(PTGS2),cysteine protease 3(CASP3),transcription factor AP-1(JUN),and protein kinase B(AKT1)were obtained by using STRING database and Cytoscape software.GO analysis and KEGG analysis respectively obtained 50 signal pathways such as peroxisome and 20 signal pathways such as lipid and atherosclerosis.Conclusion Citri Grandis Exocarpium might exhibit anti-inflammatory and anti-apoptosis effects through multiple components acting on multiple targets,thus attenuating alcoholic liver injury.