摘要
目的:采用网络药理学技术和生物信息学方法探讨旋覆代赭汤治疗胃食管反流病(GERD)的机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)、TCMID、BAT-MAN数据库筛选旋覆代赭汤活性成分和预测靶点;通过GEO数据库和R语言分析GERD差异表达基因;通过TTD、DisGeNET、GeneCards数据库筛选GERD相关靶点;采用Cytoscape 3.7.2软件构建化合物-靶点-疾病网络和靶点蛋白质-蛋白质相互作用(PPI)网络;基于DAVID数据库和R语言进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:共筛选得到旋覆代赭汤活性成分382个、预测靶点2364个;GERD基因表达分析共获得差异基因1549个;获得GERD疾病靶点2996个,与旋覆代赭汤的交集靶点共816个;根据化合物-靶点-疾病网络和PPI网络的拓扑学分析结果,筛选出白桦脂醇、姜酮、槲皮素、延胡索乙素、葫芦巴碱等36个关键药效分子和E1A结合蛋白P300(EP300)、磷脂酰肌醇3-激酶CA(PIK3CA)、肿瘤蛋白p53(TP53)、蛋白激酶B1(Akt1)、CREB结合蛋白(CREBBP)、信号传导及转录激活蛋白3(STAT3)等164个关键靶点;富集到P<0.05的GO条目1018个,涉及细胞增殖的阳性调节、细胞因子活动、炎症反应、丝裂原活化蛋白激酶(MAPK)级联等;富集到P<0.05的KEGG通路183条,涉及内分泌抵抗、核转录因子-κB(NF-κB)信号通路、含血清素的神经突触、胃酸分泌、FoxO信号通路等。结论:初步探讨了旋覆代赭汤治疗GERD的潜在作用机制和有效活性成分,为旋覆代赭汤治疗GERD的后续研究提供依据。
Objective:To explore the mechanism of Xuanfu Daizhe Decoction(XDD)in the treatment of gastroesophageal reflux disease(GERD)by network pharmacology and bioinformatics.Methods:The active components and potential targets of XDD were retrieved from TCMSP,TCMID,and BAT-MAN.Genes differentially expressed in GERD were analyzed based on GEO database and R language and GERD-related targets were screened from TTD,DisGeNET,and GeneCards.Compound-target-disease network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.7.2.The gene ontology(GO)terms and Kyoto encyclopedia of genes and genomes(KEGG)pathways were searched from DAVID database by R language.Results:A total of 382 active compounds and 2364 potential targets of XDD were screened and 1549 genes differentially expressed in GERD were obtained.Among the 2996 targets related to GERD,816 were also the targets of XDD.According to the topological analysis results of compound-target-disease network and PPI network,36 core compounds including betulin,gingerone,quercetin,tetrahydropalmatine,and trigonelline,and 164 key targets such as E1A binding protein p300(EP300),phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3CA),cellular tumor antigen p53(TP53),protein kinase B1(Akt1),CREB-binding protein(CREBBP),and signal transducers and activators of transcription 3(STAT3)were screened out.The common targets of the disease and the decoction involved 1018 GO terms(P<0.05)including positive regulation of cell proliferation,cytokine activity,inflammatory response,and mitogen-activated protein kinase(MAPK)cascade and 183 KEGG pathways(P<0.05)such as endocrine resistance,nuclear transcription factor-κB(NF-κB)signaling pathway,serotonergic synapse,gastric acid secretion,and FoxO signaling pathway.Conclusion:The study preliminarily explored the potential mechanism and active compounds of XDD in the treatment of GERD,laying a basis for future research.
作者
杜佳雪
刘绍能
DU Jia-xue;LIU Shao-neng(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国现代中药》
CAS
2021年第7期1230-1239,共10页
Modern Chinese Medicine
关键词
网络药理学
生物信息学
旋覆代赭汤
胃食管反流
靶点
network pharmacology
bioinformatics
Xuanfu Daizhe Decoction
gastroesophageal reflux
target
