基于网络药理学多数据库探讨“栀子-刺五加”药对调节重度抑郁症的作用机制  

Mechanism of Gardenia-Acanthopanax in regulating major depressive disorder based on multi-database network pharmacology

作　　者：杨法智 徐向青[2] YANG Fazhi;XU Xiangqing(Internal Medicine of Traditional Chinese Medicine,the First Clinical College of Medicine,Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250000;Third Department of Neurology,Encephalopathy Center,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan,Shandong 250000)

机构地区：[1]山东中医药大学第一临床医学院,山东济南250000 [2]山东中医药大学附属医院神经内三科、脑病中心,山东济南250000

出　　处：《河北中医》2023年第10期1732-1738,共7页Hebei Journal of Traditional Chinese Medicine

摘　　要：目的通过网络药理学方法研究“栀子-刺五加”药对调节重度抑郁症(MDD)的药理机制,为MDD的治疗提供新的辅助治疗手段。方法通过中药系统药理学数据库与分析平台(TCMSP)获取栀子、刺五加的有效成分,并通过Pubchem数据库、Swiss Target Prediction数据库获取其作用靶点;通过GeneCards数据库获取MDD的疾病靶点,再通过Bioinformatic数据库绘制“栀子-刺五加”有效成分靶点与MDD疾病靶点韦恩图获取两者的交集靶点即为潜在治疗靶点;通过STRING获取潜在治疗靶点的蛋白质-蛋白质相互作用(PPI)网络,通过Cytoscape 3.7.2软件构建PPI网络图并进行拓扑分析;借助David数据库及R语言包对潜在治疗靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;通过R语言从GEO数据库获取MDD的差异表达基因(DEGs)并进行差异分析,再通过Bioinformatic数据库获取“栀子-刺五加”调节MDD的核心DEGs并进行统计学分析。结果筛选出栀子有效成分32个,刺五加有效成分31个,有效成分靶点572个,MDD疾病靶点10033个,两者取交集共得到潜在治疗靶点497个;据Degree值筛选出核心成分有齐墩果酸(Oleanolic Acid)、熊果酸(Ursolic Acid)、烯醇酸B(Gardenolic Acid B)等;PPI网络拓扑分析显示关键治疗靶点有Akt1、白蛋白(ALB)、3-磷酸甘油醛脱氢酶(GAPDH)等;GO功能富集分析共获取条目3705个,其中生物过程(BP)3200条、细胞组分(CC)151条、分子功能(MF)334条,KEGG通路富集分析共获取180条通路;通过Bioinformatic数据库获取5个MDD的核心DEGs,分别为碳酸酐酶Ⅳ(CA4)、鲲氧化还原酶2(NQO2)、内皮PAS区域蛋白(EPAS1)、基质金属蛋白酶9(MMP-9)及麦芽糖酶糖化酶(MGAM)。结论“栀子-刺五加”调节MDD是多成分、多靶点、多通路的复杂过程,主要通过调控CA4、NQO2、EPAS1、MMP-9、MGAM等靶点,为后续MDD的中药辅助治疗研究提供重要依据。Objective To explore the mechanism of Gardenia-Acanthopanax in regulating major depressive disorder(MDD)based on multi-database network pharmacology,thus providing a new adjuvant therapy for MDD.Methods The effective ingredients of Gardenia jasminoides and Acanthopanax were obtained in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and their targets were predicted in the PubChem,and the Swiss Target Prediction.Disease targets of MDD were predicted in the GeneCards.A Venn diagram was depicted to identify the intersection dataset of key targets of Gardenia-Acanthopanax and disease targets of MDD through the Bioinformatics Database.A protein-protein interaction(PPI)network was then created using the STRING database and visualized by Cytoscape3.7.2,followed by the topological analysis.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on the identified targets of Gardenia-Acanthopanax against MDD using the Database for Annotation,Visualization and Integrated Discovery(DAVID)and the R package.Differentially expressed genes(DEGs)in MDD were obtained in the Gene Expression Omnibus(GEO)using the R package,and the core DGEs of Gardenia-Acanthopanax for the treatment of MDD were further analyzed in the Bioinformatics Database,thus illustrating the underlying mechanisms.Results A total of 32 and 31 active ingredients were screened in the Gardenia jasminoides and Acanthopanax,respectively,involving 572 drug targets of them.A total of 10033 disease targets of MDD were screened.In their interaction dataset,totally 497 key targets were obtained.Based on the Degree value,key targets of Gardenia-Acanthopanax for the treatment of MDD included oleanolic acid,ursolic acid,gardenolic acid B,etc.Topology analysis of the PPI network illustrated the key treatment targets of Gardenia-Acanthopanax for MDD,including Akt1,albumin(ALB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),etc.A total of 3705 terms were obtained by GO enrichment

关 键 词：抑郁症 栀子 刺五加 网络药理学 

分 类 号：R289.6[医药卫生—方剂学]