摘要
目的运用网络药理学研究方法筛选中药复方内异止痛方主要有效成分,并预测复方有效成分治疗子宫内膜异位症(EMs)的相关靶点,初步探讨“有效成分-靶点-通路”效应模型治疗EMs的作用机制。方法运用中药系统药理学数据库和分析平台(TCMSP)检索中药复方内异止痛方药物化学成分,根据生物利用度(OB)和类药性(DL)2个药动学参数筛选复方中有效活性成分及对应靶点;将关键词“EMs形成”录入Genecard数据库(www.genecards.org)和OMIM数据库(www.omim.org)收集疾病相关基因,并将药物与疾病靶基因取交集,利用Cytoscape构建化合物-靶点-疾病网络。将上述所获得的交集基因信息导入在线STRING软件(http://string-db.org)数据库中,利用插件CentiScape得出核心基因,进行基因本体(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。结果内异止痛方中满足生物活性的候选化学成分有221个,搜集到与疾病相关基因1388个,药物与疾病交集基因有61个。常春藤皂甙、反式性腺酸、β-谷甾醇、芒柄花黄素、豆甾醇、芍药甙、丁子香酚是作用靶点最多的有效成分。参与作用的生物过程97个,作用通路有120条。其中排在前30的核心基因有B细胞κ轻肽基因增强子核因子1(NFKB1A)、黏蛋白1(MUC1)、糖原合成酶激酶3B(GSK3B)、丝裂原活化蛋白激酶10(MAPK10)、雌激素受体2(ESR2)、锌指转录因子(SNA1)、视网膜母细胞瘤易感基因(RB1)、内皮一氧化氮合酶(NOS3)、E钙黏蛋白(CTNNE)、胱天蛋白酶9(CASP9)、髓样细胞白血病蛋白1(MCL1)、ICML1、胱天蛋白酶8(CASP8)、缺氧诱导因子1A(HIF1A)、鼠双微体基因2(MDM2)、孕激素受体(PGR)、糖皮质激素受体(NR3C1)、基质金属蛋白酶(MMP-9)、NF-KB亚基所属原癌基因(RELA)、米克基因(MYC)、过氧化物酶体增殖物激活受体(PPARG)、酪氨酸激酶受体(ERBB2)、雄激素受体(AR)、AP-1转录因子亚单位原癌基因(FOS
Objective To screen the main active ingredients of Neiyi Zhitong Prescription,a traditional Chinese medicine(TCM)compound,based on network pharmacology,and predict the relevant targets of the compound active ingredients in the treatment of endometriosis(EMs),and preliminarily explore the action mechanism of the"active ingredient-target-pathway"effect model in the treatment of EMs.Methods The traditional Chinese medicine system pharmacology database(TCMSP)and analysis platform was performed to search the chemical components of TCM-compound Neiyi Zhitong Prescription,the effective active ingredients and corresponding targets were screened by pharmacokinetic parameters of bioavailability(OB)and drug-likeness(DL).The keyword"EMs formation"was used to collect disease-related genes in the Genecard database(www.genecards.org)and the Online Mendelian Inheritance in Man(OMIM)database(www.omim.org).The intersection of drug and disease target genes was extracted,Cytoscape were performed to construct a compound-target-disease network.The intersection gene informations of obtained above were imported into the online STRING software(http://string-db.org)database,and the core genes were obtained by using the CentiScape plug-in;then gene-ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted.Results Eligible 221 candidate chemical components of Neiyi Zhitong Prescription were included,representing 1,388 EMs-related genes,and 61 intersection gene of drugs and diseases.Ivy saponin,trans-gonadic acid,β-sitosterol,formononetin,stigmasterol,paeoniflorin and butyrosin were found to be the most active components,97 biological processes were involved,and 109 pathways were found.The NFKB1A,MUC1,GSK3B,ESR2,SNA1,RB1,NOS3,CTNNE,CASP9,MCL1,ICAM1,CASP8,HIF1A,MDM2,PGR,NR3C1,MMP9,RELA,MYC,PPARG,ERBB2,AR,FOS,CTNNB1,MAPK8,ESR1,EGFR,VEGFA and IL6 were core genes,which mainly participated in Wnt,estrogen,TNF,PI3K-Akt,FoxO,p53,ErbB,MAPK,Toll receptors and NF-kappaB,JAK-STAT and RAS si
作者
朱小琳
胡晓萌
冯月男
韩延华
韩亚光
ZHU Xiaolin;HU Xiaomeng;FENG Yuenan;HAN Yanhua;HAN Yaguang(Department of Gynecology,The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 150001;Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 150040;Department of Gynecology,The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 150040)
出处
《河北中医》
2023年第3期497-503,共7页
Hebei Journal of Traditional Chinese Medicine
基金
黑龙江省教育厅优秀创新人才项目(编号:UNPYSCT-2018229)
2020年度黑龙江省博士后科研启动资助金项目(编号:LBH-Q20057)。
