基于网络药理学预测青皮治疗抑郁症的作用机制

Mechanism of action of Pericarpium Citri Reticulatae Viride in treatment of depression:A study based on network pharmacology

目的:运用网络药理学研究青皮治疗抑郁症的作用机制。方法:采用中药系统药理学分析平台(TCMSP)检索青皮的有效成分及其作用靶点;采用OMIM、GeneCards数据库检索抑郁症的疾病靶点;应用R语言等计算软件获取青皮有效成分的作用靶点和抑郁症疾病靶点的交集基因;运用Perl软件与Cytoscape 3.7.0软件联合构建青皮-有效成分-靶点-抑郁症调控网络;使用STRING构建PPI网络;应用DAVID数据分析软件和Metascape数据库,对所筛选出的“核心基因”进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,最终获得预测结果。结果:通过以上方法,获得青皮的5个有效成分,有效成分的基因靶点与抑郁症基因靶点的交集基因有30个。通过对青皮-有效成分-靶点-抑郁症调控网络的可视化分析,发现有效成分中的川陈皮素(nobiletin)所对应的交集基因最多。运用PPI网络预测到雌激素受体1(ESR1)、胱天蛋白酶3(CASP3)、过氧化物酶体增生激活受体γ(PPARG)等25个基因是青皮治疗抑郁症所干预的重要靶点。GO功能富集分析和KEGG富集分析结果显示,青皮有效成分在分子层面对抑郁症基因的干预有较好的作用。结论:青皮治疗抑郁症的机制主要是作用于ESR1、CASP3、PPARG等25个基因,并在分子层面起到改变抑郁症基因的转录翻译等作用。

Objective:To investigate the mechanism of action of Pericarpium Citri Reticulatae Viride in the prevention and treatment of depression based on network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to screen out the effective constituents of Pericarpium Citri Reticulatae Viride and their action targets;OMIM and GeneCards databases were used to screen out the disease targets of depression;R language software was used to obtain the intersecting genes of the action targets of the effective constituents of Pericarpium Citri Reticulatae Viride and the disease targets of depression;Perl software and Cytoscape 3.7.0 software were used to construct a Pericarpium Citri Reticulatae Viride-effective constituent-target-depression regulatory network,and STRING was used to construct a protein-protein interaction(PPI)network;DAVID data analysis software and Metascape database was used to perform gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Results:Five effective constituents of Pericarpium Citri Reticulatae Viride were obtained by the above methods,and there were 30 intersecting genes between the gene targets of these effective constituents and the gene targets of depression.The visual analysis of the Pericarpium Citri Reticulatae Viride-effective constituent-target-depression regulatory network showed that among the effective constituents,nobiletin had the highest number of corresponding intersecting genes.Prediction based on the PPI network showed that 25 genes,including ESR1,CASP3,and PPARG,were the important targets for Pericarpium Citri Reticulatae Viride in the treatment of depression.GO and KEGG enrichment analysis showed that the effective constituents of Pericarpium Citri Reticulatae Viride had a good interventional effect on depression genes at the molecular level.Conclusion:Pericarpium Citri Reticulatae Viride mainly acts on 25 genes including ESR1,CASP3,and PPARG in the prevention and treatment of depression and has the function of changing the transcription and translation of depression genes at the molecular level.