基于国家专利数据库和网络药理学探讨中药复方治疗溃疡性结肠炎的配伍规律及作用机制研究

Study on the compatibility rules and action mechanism of Chinese herbal compound in the treatment of ulcerative colitis based on national patent database and network pharmacology Analysis

关键词:  溃疡性结肠炎  中药复方  专利  网络药理学  数据挖掘  配伍规律

Key words:  ulcerative colitis  Chinese medicinal compound  patent  network pharmacology  data mining  law of compatibility

摘要:

[目的]通过国家专利数据库数据挖掘归纳分析出中药治疗溃疡性结肠炎（UC）的用药特点及配伍规律，然后借助网络药理学探讨高频核心药物治疗UC的潜在作用靶点及分子机制。[方法]检索并提取“中国专利公布公告”网站建库至2021年12月10日治疗UC的中药复方专利数据。应用Microsoft Excel 2010、IBM SPSS Modeler 18.0等软件，对复方进行频次统计、关联规则和聚类分析。通过中药系统药理学数据库（TCMSP）、PubChem等数据库，挖掘药物化学成分和潜在靶点；GeneCards、Drugbank和人类孟德尔遗传（OMIM）数据库获取UC相关靶点，绘制韦恩图找到药物靶点与UC靶点的交集，利用蛋白质相互作用数据库（STRING）构建蛋白质相互作用网络，筛选核心作用靶点；KOBAS 3.0网站和Metascape平台寻找核心作用靶点富集的通路和功能。[结果]国家专利数据库共筛选得到175项治疗UC的中药复方专利，包含576味药物，排名前6位的高频核心药物分别为：甘草、黄连、白术、黄芪、白及、白芍；这6味药物共涉及129个化合物、931个相关作用靶点，挖掘出治疗靶点111个、核心靶点23个；通过富集分析得到京都基因与基因组百科全书（KEGG）通路164条，基因本体（GO）生物工程716条，GO细胞组分13条，GO分子功能31条。[结论]中药复方专利治疗UC总以清热燥湿、健脾益气为主，疏肝理气、利水渗湿为辅。核心药物治疗UC具有多成分、多靶点、多通路的特点，可能是通过调控信号转导和转录激活因子3（SATA3）、肿瘤坏死因子（TNF）、白介素（IL）-6、IL-1β、丝氨酸/苏氨酸激酶1（AKT1）、JUN等靶点，及AGE-RAGE、IL-17、炎症性肠病（IBD）、辅助性T细胞17（Th17）细胞分化等信号通路发挥的作用，为后续扩展UC的临床治疗提供了研究思路，为中医药防治UC的应用奠定了分子生物学基础。

Abstract:

[Objective] The characteristics of traditional Chinese medicine (TCM) in the treatment of ulcerative colitis (UC) and its compatibility were summarized and analyzed by data mining from the national patent database,then the potential action targets and molecular mechanisms of high-frequency core drugs in the treatment of UC were explored by using network pharmacology research methods.[Methods] The patent data of Chinese herbal compound prescriptions for the treatment of UC from the establishment of the website of "China Patent Publication Announcement" to December 10,2021 were retrieved and extracted. The Microsoft Excel 2010,IBM SPSS Modeler 18.0,etc. were used for frequency statistics,association rule analysis and clustering analysis of the compound prescriptions. Mining high-frequency core pharmaceutical chemical components and potential targets through databases such as TCMSP,PubChem;GeneCards,OMIM and Drugbank databases were used to obtain UC-related targets and Venn diagram was drawn to find the intersection of high-frequency core drug action targets and UC-related targets. protein interaction network was constructed using STRING database to screen the core action targets. KOBAS 3.0 website and Metascape platform to find the pathways and functions of core action target enrichment.[Results] A total of 175 patents of Chinese medicinal compound prescriptions for the treatment of UC were obtained through national patent database screening,which contained 576 drugs. The top 6 high-frequency core drugs were:Radix Glycyrrhizae,Rhizoma Coptidis,Rhizoma Atractylodis Macrocephalae,Radix Astragali seu Hedysari,Rhizoma Bletillae,and Radix Paeoniae Alba;The six high-frequency core drugs involved a total of 129 compounds and 931 related action targets,and 111 treatment targets and 23 core targets were discovered. Through enrichment analysis,164 KEGG pathways,716 GO biological processes,13 GO cellular components and 31 GO molecular functions were identified.[Conclusion] The patent treatment of UC with traditional Chinese medicine compound prescription was mainly based on clearing heat,eliminating dampness,invigorating spleen,and replenishing qi,supplemented by soothing liver,regulating qi,and draining water and dampness. The six high-frequency core drugs have the characteristics of multi-component,multi-target and multi-channel in the treatment of UC,which may be achieved by regulating the targets such as SATA3,TNF,IL-6,IL-1β,AKT1,JUN,and TP53,as well as the AGE-RAGE signaling pathway,cancer-related pathway,IL-17 signaling pathway,TNF signaling pathway,IBD signaling pathway,and Th17 cell differentiation signaling pathway,thereby providing research ideas for the subsequent expansion of clinical treatment of UC and laying a molecular biological basis for the application of TCM in the prevention and treatment of UC.