基于网络药理学探讨牡丹皮-栀子治疗抑郁症作用机制

Exploration of the Mechanism of Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus)in the Treatment of Depression Based on Network Pharmacology

目的通过网络药理学的方法研究牡丹皮-栀子治疗抑郁症的作用机制。方法该文通过计算机技术筛选牡丹皮、栀子治疗抑郁症的主要活性成分及其潜在作用靶点,探讨其抗抑郁作用的药理学机制。应用中药系统药理学数据库与分析平台(TCMSP)和Uniport数据库整理及筛选牡丹皮、栀子的有效成分和作用靶点及对应的基因名。通过GeneCards数据库、在线人类孟德尔遗传数据库(OMIM)、靶点预测数据库(TTD)提取抑郁症(depressive disorder,DD)的相关靶点基因。进行Venn分析,将成分靶点与抑郁症疾病靶点取交集,获得共同靶点基因。构建化合物-靶点复合网络,筛选发挥抗抑郁作用的关键成分,同时用共同靶点基因构建蛋白互作网络(PPI)筛选出关键蛋白。将Metascape数据库和微生信云平台筛选得到的共同靶点基因进行京都基因和基因组百科全书(KEGG)与基因本体(GO)通路富集分析,再通过KEGG数据库画出KEGG信号通路图。结果筛选得到牡丹皮、栀子与抑郁症有关的15个活性成分、138个对应靶点;PPI网络涉及138个节点,1648条边;GO富集主要涉及对氧气水平反应、细胞膜筏、DNA结合转录因子活性的调节。KEGG富集气泡图显示与癌症通路、脂质与动脉粥样硬化通路、PI3K-Akt信号通路等相关通路有关。结论通过网络药理学可以分析出牡丹皮、栀子在治疗抑郁症方面的有效化合物和关键通路等,为牡丹皮、栀子治疗抑郁症的临床研究提供了理论依据。

Objective To study the mechanism of Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus)in the treatment of depression by network pharmacology.Methods In this paper,the main active components and potential targets of Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus)in the treatment of depression were screened by computer technology,and the pharmacological mechanism of their antidepressant effects was discussed.Traditional Chinese Medicine Systems Pharmacology Database(TCMSP database)and Uniport database were used to sort out and screen the effective components,targets and corresponding gene names of Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus).The related target genes of depressive disorder were extracted from GeneCards database,Online Human Mendelian genetic database(OMIM database)and Target Prediction Database(TTD database).Venn analysis was performed to intersect the component targets with the depression disease targets to obtain common target genes.The compound-target complex network was constructed to screen the key components of antidepressant effect,and the protein interaction network(PPI)was constructed with common target genes to screen the key proteins.The Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)pathway enrichment analysis were performed using the screened common target genes in the Metascape database and the Weisheng Xinyun platform,and then the KEGG signal pathway map was drawn through the KEGG database.Results 15 active components and 138 corresponding targets related to depression were screened out from Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus).PPI network involves 138 nodes and 1648 edges;GO enrichment mainly involves the response to the decrease of oxygen content in hypoxic responders,the regulation of cell membrane rafts,and the activity of DNA-binding transcription factors.KEGG enrichment bubble diagram showed that it was related to cancer pathway,lipid and atherosclerosis pathway,PI3K-Akt signaling pathway and other related pathways.Conclusion The effective compounds and key pathways of Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus)in the treatment of depression can be analyzed by network pharmacology,which provides a theoretical basis for the clinical study of Mudanpi(Moutan Cortex)-Zhizi(Gardeniae Fructus)in the treatment of depression.