基于网络药理学的青黛治疗溃疡性结肠炎作用机制研究  

Potential Mechanism of Indigo Naturalis in Treatment of Ulcerative Colitis Based on Network Pharmacology

作　　者：王依 史瑞[2] 李军祥[2] 刘豫玥[2] 袁亚利 万雯 WANG Yi;SHI Rui;LI Jun-xiang;LIU Yu-yue;YUAN Ya-li;WAN Wen(Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学东方医院,北京100078

出　　处：《中国现代中药》2021年第8期1416-1422,共7页Modern Chinese Medicine

基　　金：国家重点研发计划项目(2018YFC1705405);北京中医药大学青年教师项目(2019-JYB-JS-119)。

摘　　要：目的:利用网络药理学方法探究青黛治疗溃疡性结肠炎(UC)的作用机制,为临床上应用青黛治疗UC提供参考。方法:检索中药系统药理学数据库与分析平台(TCMSP)、UniProt、GeneCards、OMIM数据库,筛选出青黛治疗UC的有效化学成分及靶点,并建立可视化网络模型;利用Cytoscape 3.7.0软件绘制成分-靶点网络关系图,并分析青黛治疗UC的核心靶点;采用Metascape基因注释工具对靶点进行生物通路富集分析。结果:共筛选出青黛化学成分29个,其中与UC相关的有效成分7个,分别是10H-吲哚并[3,2-b]喹啉、异靛蓝、靛蓝、6-(3-氧代吲哚-2-亚甲基)吲哚并[2,1-b]喹唑啉-12-酮、靛玉红、β-谷甾醇、异维他嗪;成分对应的治疗UC作用靶点18个,包括环加氧酶1(PTGS1)、雌激素受体1(ESR1)、丝氨酸蛋白酶1(PRSS1)、雄激素受体(AR)、糖原合成酶激酶-3β(GSK3B)、细胞有丝分裂检验点激酶1(CHEK1)、过氧化物酶增殖激活受体γ(PPARG)、乙酰胆碱酯酶(ACHE)、代谢活化酶细胞色素P450-1A1(CYP1A1)、方烃受体(AHR)、B细胞淋巴瘤-2(Bcl-2)、半胱氨酸蛋白酶-3(CASP3)、半胱氨酸蛋白酶-8(CASP8)、半胱氨酸蛋白酶-9(CASP9)、蛋白激酶C-α(PRKCA)、对氧磷酶1(PON1)、转录因子p65(RELA)、B细胞κ轻肽基因增强子抑制因子激酶β(IKBKB);上述有效成分及靶点经Cytoscape 3.7.0网络可视化后筛选出包括靛玉红、β-谷甾醇、异维他嗪在内的关键成分与PTGS1、ESR1、PRSS1、CASP3、CASP8、CASP9在内的核心基因;生物富集分析显示,青黛可能主要参与外源性凋亡信号通路、对有毒物质的反应、对有机环化合物的反应、对抗生素的反应、对类固醇激素的反应及参与调节外源性凋亡信号通路等生物过程,通过调控凋亡、p53、白细胞介素-17(IL-17)等信号通路发挥治疗UC的作用。结论:通过网络药理学预测青黛可能是通过抑制肠道细胞凋亡、抑制肠道炎症症状、促进受损黏膜修复�Objective:To explore the mechanism of Indigo Naturalis in the treatment of ulcerative colitis(UC)by means of network pharmacology and thereby lay a theoretical basis for clinical application of Indigo Naturalis in the treatment of UC.Methods:Active components and targets of Indigo Naturalis were retrieved based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),UniProt,Genecards,and OMIM and a Venn diagram showing the common targets of the disease and the medicinal was plotted.The medicinal-component-target-disease network was constructed by Cytoscape 3.7.0 to yield the hub genes related to the treatment of UC by Indigo Naturalis,followed by the gene ontology(GO)term enrichment and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment of the hub genes with Metascape.Results:A total of 29 active components of Indigo Naturalis were screened,of which 7 were related to UC:10H-indolo[3,2-b]quinolone,isoindigo,indigo,6-(3-oxoindolin-2-ylidene)indolo[2,1-b]quinazolin-12-one,indirubin,beta-sitosterol,isovitexin.Indigo Naturalis shared 18 targets with the disease:prostaglandin-endoperoxide synthase 1(PTGS1),estrogen receptor 1(ESR1),serine protease 1(PRSS1),androgen receptor(AR),glycogen synthase kinase 3 beta(GSK3B),checkpoint kinase 1(CHEK1),peroxisome proliferator-activated receptor gamma(PPARG),acetylcholinesterase(ACHE),cytochrome P4501A1(CYP1A1),aryl hydrocarbon receptor(AHR),B cell lymphoma-2(Bcl-2),caspase-3(CASP3),caspase-8(CASP8),caspase-9(CASP9),protein kinase Cα(PRKCA),paraoxonase 1(PON1),transcription factor p65(RELA),IκB kinaseβ(IKBKB).The key components were indirubin,β-sitosterol,isovitexin etc.,and the hub genes included PTGS1,ESR1,PRSS1,CASP3,CASP8,and CASP9.The hub genes mainly involved in the GO terms of extrinsic apoptotic signaling pathway,response to toxic substance,response to organic compound,response to antibiotic,response to steroid hormone,and negative regulation of extrinsic apoptotic signaling pathway,and the pathways of apoptosis,IL^(-1)7

关 键 词：网络药理学 青黛 溃疡性结肠炎 作用机制 

分 类 号：R285.5[医药卫生—中药学]