基于生物信息技术探究藿香正气液治疗COVID-19的机制  

Mechanism of Huoxiang Zhengqi Oral Liquid in the treatment of COVID-19 based on biological information technology

作　　者：顾昱昊 陈可点 戚蕊 卢明军 皮雯敏 谢以清 高丰 戴子琦 吴倩文 霍苏 徐意 徐冰[1] 雷海民[1] GU Yuhao;CHEN Kedian;QI Rui;LU Mingjun;PI Wenmin;XIE Yiqing;GAO Feng;DAI Ziqi;WU Qianwen;HUO Su;XU Yi;XU Bing;LEI Haimin(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100102,China;Beijing Tongrentang Limited Company,Beijing 100062,China)

机构地区：[1]北京中医药大学,北京100102 [2]北京同仁堂科技发展股份有限公司,北京100062

出　　处：《西北药学杂志》2022年第2期44-50,共7页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81173519、81603256);新冠肺炎防控应急专项(编号:2020-JYB-YJ-007);北京高精尖学科-系统中药学项目、中央高校基本科研经费项目(编号:2020-JYB-XJSJJ-007);北京市中药基础与新药研究重点实验室项目;中国科学院青年人才培养项目(编号:CACM-2018-QNRC2-B08);北京同仁堂科技发展股份有限公司委托课题(编号:G20-01-080)。

摘　　要：目的探究藿香正气液(HXZQ)治疗新型冠状病毒肺炎(coronavirus disease 19,COVID-19)的网络调控机制。方法通过SymMap、TCMSP数据库筛选药物的归经、有效成分;输入Pharm Mapper数据库、DrugBank数据库、SwissTarget数据库获得相应基因;检索GeneCards数据库获得COVID-19的靶点基因;利用R语言3.6.1截取交集网络获得候选靶点;借助Cytoscape 3.7.1将归经-中药-化合物-靶点-疾病网络进行可视化处理;在STRING平台上构建蛋白-蛋白相互作用(protein-protein interaction,PPI)网络并导入Cytoscape 3.7.1完成图像处理;利用DAVID数据库对候选靶点进行GO(gene ontology)富集分析和KEGG(Kyoto encyclopedia of genes and genomes)通路注释;用AutoDock Vina 4.2.6将关键靶点与关键成分进行分子对接,并用PyMol进行可视化处理。结果获得164种有效化合物、443个不重复的靶标、67个疾病治疗靶点。GO功能富集得到GO条目173个(P<0.05),其中生物过程(biological process,BP)条目126个,细胞组成(cellular component,CC)条目22个,分子功能(molecular function,MF)条目25个;KEGG通路富集得到114条信号通路(P<0.05)。结论藿香正气液中的有效成分槲皮素、β-谷甾醇、柚皮素、汉黄芩苷、山柰酚、2-hydroxyisoxypropyl-3-hydroxy-7-isopentene-2,3-dihydrobenzofuran-5-carboxylic和甘乌内酯等可能通过调控肿瘤坏死因子信号通路、鞘脂信号通路和缺氧诱导因子-1信号通路中的MAPK1、MAPK3、RelA等关键靶点,干预多个与抗炎、免疫杀伤和重塑气道等相关的生物功能,从而发挥治疗COVID-19的作用。Objective To explore the network regulation mechanism of Huoxiang Zhengqi Oral Liquid(HXZQ)in the treatment of coronavirus disease 19(COVID-19).Methods The channel tropism and the active components of HXZQ were searched by SymMap and TCMSP databases.And the corresponding genes were obtained by Pharm Mapper,DrugBank,and SwissTarget databases.The related targets of COVID-19 were obtained by GeneCards database.And the R language 3.6.1 was used to complete the intersection network to obtain candidate targets.The channel tropism-traditional Chinese medicine-compound-targetdisease network was constructed by Cytoscape 3.7.1 software,and the protein-protein interaction(PPI)network was constructed by STRING platform.GO(gene ontology)functional enrichment analysis and KEGG(Kyoto encyclopedia of genes and genomes)pathway enrichment analysis were conducted by DAVID database.The molecular docking of key targets and key components was completed by using AutoDock Vina 4.2.6.And PyMol was used for visualization.Results 164 effective compounds,443 unique target information,and 67 disease treatment targets were obtained.GO function enrichment resulted in 173 GO entries(P<0.05),including 126 biological process(BP)entries,22 cell composition(CC)entries and 25 molecular function(MF)entries;KEGG pathway enrichment yielded 114 entries signal pathway(P<0.05).Conclusion The active ingredients in HXZQ are quercetin,β-sitosterol,naringenin,wogonin,kaempferol,2-hydroxyisoxypropyl-3-hydroxy-7-isopentene-2,3-dihydrobenzofuran-5-carboxylic and glyuranolide.These components can regulate tumor necrosis factor,toll-like receptor,sphingolipid,and hypoxia-inducible factor-1 signaling pathways.These components affect key targets such as MAPK1,MAPK3,and RelA in the pathways,and then interfere with multiple biological functions related to anti-inflammatory,immune killing,airway remodeling,etc.,so as to play a role in the treatment of COVID-19.

关 键 词：藿香正气液 新型冠状病毒肺炎 作用机制 分子对接 

分 类 号：R965[医药卫生—药理学]