文献类型：期刊文献

中文题名：基于数据挖掘及网络药理学方法探讨含当归中药复方抗肝纤维化的用药规律及作用机制

英文题名：Exploring the Rule of Medication and Mechanism of Action of Compounds Containing Angelicae sinensis Radix against Hepatic Fibrosis Based on Data Mining and Network Pharmacology Methods

作者：韦凌霞[1];丁茂鹏[1];王志旺[1];王瑞琼[1];姚楠[1];庞亚蓉[1]

第一作者：韦凌霞

机构：[1]甘肃中医药大学药学院,兰州730000

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2020

卷号：31

期号：11

起止页码：1323

中文期刊名：中药新药与临床药理

外文期刊名：Traditional Chinese Drug Research and Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：国家自然科学基金项目(81860787,81660653);甘肃省高等学校科研基金项目(2015A-096)。

语种：中文

中文关键词：含当归中药复方;肝纤维化;用药规律;作用机制;数据挖掘;黄芪;丹参;网络药理学

外文关键词：Angelicae sinensis radix containing compounds;hepatic fibrosis;rule of medication;mechanism of action;data mining;Astragals radix;Salviae miltiorrhizae radix et rhizoma;network pharmacology

摘要：目的采用数据挖掘及网络药理学方法分析含当归中药复方抗肝纤维化(HF)的用药规律,并探讨核心中药可能的作用机制。方法利用CNKI、万方等数据库收集治疗肝纤维化临床研究的含当归中药复方,应用SPSS Statistics 24.0软件对纳入标准的中药进行频次、性味归经、四气五味及其功效分类统计,并对频数大于10的中药进行系统聚类分析。使用中药系统药理学分析平台数据库(TCMSP)对频数较高且在聚类分析中聚为一类的配伍中药进行成分、靶点筛选,将其靶点与在GeneCards数据库筛选得到的肝纤维化疾病靶点进行匹配,获取高频中药抗肝纤维化的关键靶点;采用STRING平台、DAVID数据库对关键靶点进行蛋白相互作用(PPI)网络分析及京都基因与基因组百科全书(KEGG)通路富集分析;最后通过Cytoscape 3.6.1软件构建中药-活性成分-关键靶点-通路网络,并进行拓扑分析。结果共获得符合标准的中药复方121首,涉及156味中药;其中以补虚药、活血化瘀药多见,以归肝、脾经居多,以寒温平、甘苦辛为主;当归、黄芪、丹参累计频次最高且聚为一类。获得当归、黄芪及丹参活性成分共75个,核心成分包括铁蛋白、阿魏酸、7,10-戊二酸、木犀草素、山奈酚、毛蕊异黄酮、槲皮素等;抗肝纤维化关键靶点90个,核心靶点包括IL-6、TNF、MMP9、JUN、SRC、MAPK8、MMP2、F2、SERPINE1、ELANE等;涉及104条通路,主要通路包括癌症通路、PI3K-Akt信号通路、TNF信号通路、乙型肝炎、HIF-1信号通路、Toll样受体信号通路等。结论治疗肝纤维化的中药复方中以补虚药多见,常配伍活血化瘀药,与治疗肝纤维化"益气养阴、活血化瘀"的基本治法相一致。当归、黄芪、丹参配伍在抗肝纤维化复方中最常见,其可能主要通过阿魏酸、山奈酚、槲皮素、毛蕊异黄酮、木犀草素等活性成分,作用于IL-6、TNF、MMP9、MAPK8等关键靶点,及PI3K-Akt信号通路、TNF信号通路、HIF-1信号通路、Toll样受体信号通路等,共同发挥抗肝纤维化的作用。
Objective To analyze the rule of medication of compound containing Angelicae sinensis radix against hepatic fibrosis(HF) by data mining and network pharmacology methods,and to explore the possible mechanism of action of core traditional Chinese medicines(TCM).Methods All compounds of clinical study that containing Angelicae sinensis radix treating HF were collected from CNKI,Wanfang and other databases.The SPSS Statistics24.0 software was used to categorize the statistics of the frequency,nature and flavour and meridian tropism,four properties and five flavors,and their efficacy of TCM.And the TCM with frequencies of application greater than 10 were selected and systematically clustered and analyzed.The TCM with higher frequencies and being clustered together were searched for their components and targets through the TCMSP database;and those matched with the target(s) of anti-HF were searched in the GeneCards database to obtain the key targets of the high-frequency TCM with anti-HF efficacy.The key targets were then used to construct and analyze PPI network and KEGG pathway with STRING and DAVID database.Finally,the TCM,active ingredients,key targets,pathway networks and topology were constracted and anahyzed with Cytoscape software.Results A total of 156 TCM in the 121 compounds that met the standard were obtained,among which,TCM that restoring deficiency,and invigorating blood circulation and eliminating stasis,with liver and spleen tropism,cold,warm and smooth properties,bitter and pungent in flavor,were shown the most common.The Angelicae sinensis radix,Astragali radix,Salviae miltiorrhizae radix et rhizoma were the most frequently used and being clustered together.There were 75 active components and 90 key targets,among which the core components were ferritin,ferulic acid(CIS),7,10-pentadecadiynoic acid,luteolin,kaempferol,calycosin,quercetin,etc.The core targets were IL-6,TNF,MMP9,JUN,SRC,MAPK8,MMP2,F2,SERPINE1,ELANE,etc.And 104 signaling pathways were found participated in the anti-HF process,which were pathways involving cancer,PI3 K-Akt pathway,TNF pathway,hepatitis B,HIF-1 pathway,Toll-like receptor pathway,and so on.Conclusion Commonly used TCM for HF were those could restore deficiency,and often combined with drugs invigorating blood circulation and eliminating stasis,which is consistent with the basic treatment principle that of HF(tonifying qi,nourishing yin,and promoting blood circulation).The compatibility of Angelica sinensis,Astragali radix,Salviae miltiorrhizae radix et rhizoma was the most common compound for antiHF.It may be mainly through ferulic acid,kaempferol,quercetin,calycosin,luteolin and other active ingredients to act on key targets such as IL-6,TNF,MMP9,MAPK8,etc.,and PI3 K-Akt,TNF,HIF-1,Toll-like receptor and other signaling pathways,to take anti-HF effects together.