摘要
目的:基于数据库挖掘,分析以丁香为核心治疗腹泻的高频配伍规律,并利用网络药理学阐释含丁香核心药物组治疗腹泻的作用机制。方法:应用Python 3.8.1编程对中国中医药数据库进行智能抓取,分析丁香配伍规则,以符合支持度(support)≥0.30,置信度(confidence)≥0.90且提升度(lift)≥1.00的中药设为丁香核心药物组,利用中药系统药理学数据库与分析平台(TCMSP)检索成分并筛选成分靶点,以"Diarrhea"为关键词在Therapeutic Target Datebase(TTD),GeneCards,DisGeNET数据库搜集疾病靶点,运用Cytoscape 3.7.1软件构建"中药-成分-潜在靶点"网络图,通过STRING 11.0构建蛋白质-蛋白质相互作用(PPI)网络,利用R语言对潜在靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,采用Discovery Studio Client 2016对核心药物组的成分进行初步验证和评估。结果:数据库筛选获得含丁香治疗腹泻的方剂155首,涉及54味中药,关联规则分析表明在治疗腹泻的配伍中,丁香与木香、甘草、肉豆蔻、白术具有强关联性,以这5味中药组成的核心药物组共涉及119种中药成分和114个潜在靶点,其中104个潜在靶点分布在神经系统,关键靶点有肿瘤蛋白P53(TP53),JUN原癌基因(JUN),丝裂原活化蛋白激酶8(MAPK8),白细胞介素-6(IL-6),90 kDa热休克蛋白αA1(HSP90AA1)等。GO富集分析主要涉及神经递质水平的调节、血液循环过程、激素介导的信号途径、化学突触传递的调节等生物学过程,KEGG通路中IL-17信号通路、辅助性T细胞17(Th17)分化、表皮生长因子受体、沙门氏菌感染等与治疗腹泻密切相关。分子对接显示关键靶蛋白与槲皮素、山柰酚以及β-谷甾醇具有较高亲和力。结论:含丁香核心药物组涉及的多成分、多靶点、多通路与炎症、神经系统密切相关,推测其可能通过修复肠道屏蔽完整性、调节神经递质水平来治疗腹泻。
Objective: Based on database mining,the high-frequency compatibility of Caryophylli Fols as the core in formulas for treating diarrhea was analyzed,and the network pharmacology was used to elucidate the mechanism of the core drug group containing Caryophylli Fols in the treatment of diarrhea.Method:The online database of traditional Chinese medicine(TCM)was intelligently crawled by Python 3.8.1 programming,and the compatibility rules of Caryophylli Fols were analyzed,and the TCM with support≥0.30,confidence≥0.90 and lift≥1.00 was set as the core drug group of Caryophylli Fols. The components were searched and screened by TCM Systems Pharmacology Database and Analysis Platform(TCMSP),and the disease targets were collected in Therapeutic Target Datebase(TTD), GeneCards and DisGeNET database with "Diarrhea" as the key word. The network diagram of "TCM-ingredients-potential targets" was constructed by Cytoscape 3.7.1 software,and the network of protein-protein interaction(PPI)was constructed by STRING11.0. Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of potential targets was analyzed by R language,and the components of the core drug group were preliminarily verified and evaluated by Discovery Studio Client 2016 software. Result: A total of 155 formulas containing Caryophylli Fols for treating diarrhea were screened,involving 54 TCMs. The analysis of association rules showed that Caryophylli Fols was strongly associated with Myristicae Semen,Glycyrrhizae Radix et Rhizoma,Aucklandiae Radix and Atractylodis Macrocephalae Rhizoma in the treatment of diarrhea. The core drug group composed of these five TCMs involved 119 kinds of TCM ingredients and 114 potential targets,of which 104 potential targets were distributed in the nervous system,and the key targets were tumor protein p53(TP53),transcription factor activator protein-1(JUN),mitogen-activated protein kinase 8(MAPK8),interleukin-6(IL-6),90 kDa heat shock protein αA1(HSP90 AA1)and so on. GO enrichment analysis mainly involved biological processes such as the regulation of neurotransmitter levels,blood circulation,hormone-mediated signal pathway and regulation of chemical synaptic transmission. IL-17 signal pathway, helper T cell 17(Th17)cell differentiation,epidermal growth factor receptor and salmonella infection in KEGG pathways were closely related to the treatment of diarrhea. Molecular docking showed that the key target protein had high affinity with quercetin,kaempferol and β-sitosterol. Conclusion: The multi-components,multi-targets and multi-pathways involved in the core drug group of Caryophylli Fols are closely related to inflammation and nervous system,so it is speculated that it may treat diarrhea by repairing intestinal shielding integrity and regulating the levels of neurotransmitters.
作者
陈青垚
王梁凤
李慧婷
王堯
柳小莉
徐杰
杨明
王芳
张小飞
CHEN Qing-yao;WANG Liang-feng;LI Hui-ting;WANG Yao;LIU Xiao-li;XU Jie;YANG Ming;WANG Fang;ZHANG Xiao-fei(Key Laboratory of Modern Preparation of Traditional Chinese Medicine(TCM),Ministry of Education,Jiangxi University 0f TCM,Nanchang 330004,China;College of Pharmacy,Chengdu University of TCM,Chengdu 610075,China;College of Pharmacy.Shanxi University of Chinese Medicine,Xianyang 712046,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第5期158-170,共13页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81960714)
江西省重大科技研发专项(20194ABC28009)
江西中医药大学“双一流”学科建设项目(JXSYLXK-ZHYAO083,JXSYLXK-ZHYAO084)
现代中药制剂教育部重点实验室2017年开放基金项目(2017003)。
关键词
数据挖掘
网络药理学
腹泻
丁香
炎症
脑肠互动
方剂
data mining
network pharmacology
diarrhea
Caryophylli Fols
inflammation
braingut interaction
formulas
