基于网络药理学分析青蒿素治疗炎症性肠病的靶点及机制  

Analysis of the targets and mechanisms of artemisinin in the treatment of inflammatory bowel disease based on network pharmacology

作　　者：雷玉婷 杨艳红[2] 雷自立 LEI Yuting;YANG Yanhong;LEI Zili(Institute of Chinese Medicinal Sciences,Guangdong Pharmaceutical University,Guangzhou 510006,China;The First Affiliated Hospital(School of Clinical Medicine),Guangdong Pharmaceutical University,Guangzhou 510080,China)

机构地区：[1]广东药科大学中医药研究院,广东广州510006 [2]广东药科大学附属第一医院(临床医学院),广东广州510080

出　　处：《广东药科大学学报》2021年第6期26-34,共9页Journal of Guangdong Pharmaceutical University

基　　金：国家自然科学基金项目(81803912,31671520);广州市越秀区教育卫生专项项目(2018-WS-011);中国科学院再生生物学重点实验室开放课题(KLRB201807)。

摘　　要：目的运用网络药理学来探讨青蒿素治疗炎症性肠病(inflammatory bowel disease, IBD)的靶点及机制。方法在Pubchem数据库中获取青蒿素的SMILES(simplified molecular input line entry specification,简化分子线性输入规范),通过查找Swiss Target Prediction数据库、PharmMapper数据库和DrugBank数据库选出青蒿素靶点。通过TTD数据库(therapentic target database)、Drugbank数据库和DisGeNET数据库收集IBD靶点。通过韦恩图交集筛选出青蒿素直接作用于IBD的靶点,将这些直接作用靶点输入STRING数据库进行蛋白相互作用分析获得蛋白相互作用网络;输入DAVID数据库进行GO功能和KEGG通路富集分析。利用Real-time PCR和16S rDNA基因分析对部分信号通路进行了验证。结果经过分析得到青蒿素靶点341个、IBD靶点1 629个,交集分析得到青蒿素直接作用于IBD的靶点84个,其中GO分析共得到288条功能,包括189个生物学过程、31个细胞组分和68个分子功能;72条KEGG通路,包括肠上皮连接相关通路,如黏着斑连接、黏附连接和一些炎症应激相关通路,如趋化因子信号通路、T细胞受体信号通路、NOD样受体信号通路等。与对照组相比,葡聚糖硫酸钠盐(dextran sulfate sodium salt,DSS)诱导的IBD小鼠肠道组织中E-cardherin表达水平显著降低,用双氢青蒿素(dihydroartemisinin, DHA)处理后,E-cardherin有恢复上调的趋势。肠道菌群测序结果表明在门水平上,与对照组小鼠相比,DSS组的Bacteroidales;24-7;roup丰度显著降低,而给予DHA处理后,丰度明显升高。结论青蒿素通过多个靶点和信号通路发挥抗炎作用,并且作用于多个信号通路修复肠道屏障,为探讨青蒿素治疗IBD提供思路。Objective To study the targets and mechanisms of artemisinin in the treatment of inflammatory bowel disease(IBD) based on network pharmacology. Methods The SMILES(Simplified molecular input line entry specification) of artemisinin was obtained from Pubchem. The targets of artemisinin were filtered out by searching the Swiss Target Prediction database, the PharmMapper database and the DrugBank database. The targets of IBD were collected by TTD database(Therapentic Target Database), Drugbank database and DisGeNET database. The direct action targets of artemisinin on IBD were screened by Wayne diagram intersection. These direct targets were input into STRING database for protein interaction analysis to obtain protein interaction network, and these targets were input into DAVID database for GO function and KEGG pathway enrichment Set analysis. Some signal pathways were verified by Real-time PCR and 16 S rDNA gene analysis. Results 341 artemisinin targets and 1629 IBD targets were obtained by analysis, and 84 artemisinin targets directly acting on IBD were obtained by intersection analysis. The result of GO analysis demonstrated a total of 288 functions, including 189 biological processes, 31 cell components and 68 molecular functions. The results of KEGG analysis showed 72 pathways,including "Focal adhesion", "Adherens junction", "Chemokine signaling pathway","T cell receptor signaling pathway" and "NOD-like receptor signaling pathway". Compared with the control group, the expression level of E-cardherin in the intestinal tissue of IBD mice induced by dextran sulfate sodium salt(DSS) downregulated significantly, while after treatment with dihydroartemisinin(DHA), the expression of E-cardherin showed a trend of up regulation. The results of 16 S rDNA sequencing analysis showed that on Phylum level, the abundance level of Bacteroidales;24-7;roup had decreased in the DSS group compared with the control group, but it had increased after treatment of DHA. Conclusion Artemisinin plays an anti-inflammatory role by multiple

关 键 词：青蒿素 炎症性肠病 网络药理学 信号通路 作用机制 

分 类 号：R285[医药卫生—中药学]