文献类型：期刊文献

中文题名：基于网络药理学和分子对接技术探讨解毒活血汤治疗新型冠状病毒肺炎的潜在作用机制

英文题名：Analysis of potential mechanism of Jiedu Huoxue Tang(解毒活血汤) in the treatment of COVID-19 based on network pharmacology and molecular docking technology

作者：吕鑫[1];顾志荣[2];张志红[3];祁梅[2];张锐[1];葛斌[2]

第一作者：吕鑫

机构：[1]甘肃中医药大学药学院,甘肃兰州730101;[2]甘肃省人民医院药剂科,甘肃兰州730000;[3]甘肃中医药大学期刊编辑部,甘肃兰州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：2022

卷号：39

期号：4

起止页码：34

中文期刊名：甘肃中医药大学学报

外文期刊名：Journal of Gansu University of Chinese Medicine

基金：甘肃省中医药管理局科研项目(GZK-2019-41);甘肃省人民医院研发攻关项目(18GSSY2-3)。

语种：中文

中文关键词：解毒活血汤;新型冠状病毒肺炎;网络药理学;分子对接;作用机制

外文关键词：Jiedu Huoxue Tang(解毒活血汤,JDHXT);coronavirus disease 2019(COVID-19);network pharmacology;molecular docking technology;mechanism

摘要：目的 运用网络药理学方法和分子对接技术探讨解毒活血汤治疗新型冠状病毒肺炎(COVID-19)多成分、多靶点、多通路的作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)检索解毒活血汤中除生地黄外9味中药的活性成分及靶点,查阅文献筛选生地黄的活性成分,使用GeneCards数据库获取COVID-19的靶点,通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape 3.7.2软件构建药物-化合物-靶点网络,通过R软件的ClusterProfiler包对关键靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,最后对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)3CL水解酶(Mpro)、血管紧张素转化酶Ⅱ(ACE2)及关键靶点与显著化合物进行分子对接。结果 解毒活血汤包含了10味中药、153个化合物和253个靶点,将解毒活血汤主要活性成分调控的靶点与COVID-19的治疗靶点取交集,得到51个潜在靶点,GO功能富集分析得到82个条目(P<0.05),KEGG通路富集分析筛选得到154条信号通路(P <0.05);分子对接结果显示,Mpro与槲皮素、ACE2与木犀草素、胱天蛋白酶3(CASP3)与槲皮素、丝裂原活化蛋白激酶3(MAPK3)与木犀草素、丝裂原活化蛋白激酶1(MAPK1)与汉黄芩素、丝裂原活化蛋白激酶8(MAPK8)与山奈酚、白细胞介素-6(IL-6)与木犀草素对接结果较好。结论 解毒活血汤治疗COVID-19的作用机制可能与其多个化学成分通过多靶点、多通路参与抗炎、抗病毒和免疫调节等作用有关。
Objective To explore the action mechanism of multi-component,multi-target,and multi-pathway of Jiedu Huoxue Tang(解毒活血汤,JDHXT)in the treatment of COVID-19 by using network pharmacology methods and molecular docking technology.Methods The active components and targets of 9 flavors of Chinese materia medica(CMM)of JDHXT except Rehmanniae radix were retrieved via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the active components of Rehmanniae radix were screened out by consulting literature.COVID-19 targets were obtained via the GeneCards database.A protein-protein interaction(PPI)network was constructed via the STRING database.Cytoscape 3.7.2 software was used to construct a drug-component-target network.The gene ontology(GO)enrichment analysis and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of the key targets was performed via the ClusterProfiler package of R software.Finally,molecular docking of Mpro,angiotensin-converting enzyme 2(ACE2),and key targets of SARS-CoV-23CL with significant compounds was performed.Results JDHXT contained 10 flavors of CMM,153 compounds and 253 targets.The targets of the main active compounds of JDHXT were intersected with the therapeutic targets of COVID-19,and 51 key targets were obtained.GO function enrichment analysis yielded 82 GO entries(P<0.05),and KEGG pathway enrichment analysis generated 154 signal pathways by screening(P<0.05).The docking results showed that Mpro with quercetin,ACE2 with luteolin,cycteine aspartate-specific protease-3(CASP3)with quercetin,mitogen-activated protein kinase(MAPK)3 with luteolin,MAPK1 with wogonin,MAPK8 with kaempferol,and interleukin(IL)-6 with luteolin had better docking results.Conclusion The mechanism of JDHXT in the treatment of COVID-19 may be related to the anti-inflammatory,antiviral and immunomodulatory effects of many chemical components through multi-targets and multiple pathways.