基于网络药理学和分子对接技术的宣肺达郁汤用于新型冠状病毒肺炎恢复期治疗的作用机制研究  

Mechanism of Xuanfei Dayu Decoction in Treating the Recovery Stage of COVID-19 Based on Network Pharmacology and Molecular Docking Technology

作　　者：吕楠 岳宝森 张炜华 田欢 杨帅 职媛 吴筱菁 王巧玲 赵锋 Lv Nan;Yue Baosen;Zhang Weihua;Tian Huan;Yang Shuai;Zhi Yuan;Wu Xiaojing;Wang Qiaoling;Zhao Feng(Xi’an Hospital of Traditional Chinese Medicine,Xi'an 710021,China)

机构地区：[1]西安市中医医院,西安710021

出　　处：《中国药师》2021年第11期2002-2011,共10页China Pharmacist

基　　金：陕西省中医药管理局陕西省第二批中医药防治新冠肺炎科研应急专项资助项目(编号:SZY-KJCYC-2020-YJ011);陕西省名中药师赵锋传承工作室建设项目(编号:201836)。

摘　　要：目的:应用网络药理学和分子对接技术分析宣肺达郁汤用于新型冠状病毒肺炎(COVID-19)恢复期治疗的关键活性成分及核心作用靶点,并探讨其潜在作用机制。方法:查询中国药典、TCMSP和TCM@Taiwan数据库,获取宣肺达郁汤复方中11味中药的性味归经、活性成分及作用靶点,应用GeneCards及OMIM数据库查询COVID-19恢复期疾病治疗靶点,运用Venny软件对中药及疾病靶点取交集,获得与COVID-19恢复期治疗相关的宣肺达郁汤潜在作用靶点。利用Cytoscape软件构建中药-性味归经、中药-活性成分-靶点网络,应用STRING数据库对共有靶点进行蛋白质相互作用(PPI)分析,根据节点属性值筛选获取宣肺达郁汤中关键活性成分和核心作用靶点。通过Metascape、DAVID数据库对共有靶点进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)信号通路、组织表达富集分析。借助AutoDockTools软件研究关键活性成分与成纤维细胞生长因子受体(FGFR)、血管内皮生长因子受体2(VEGFR2)间的亲和作用。结果:宣肺达郁汤性平,味甘,主要归肺、脾、心经。与COVID-19恢复期治疗相关的宣肺达郁汤活性成分共137个,对应231个靶点,潜在作用靶点主要分布于肺组织,关键活性成分为槲皮素、木犀草素、山奈酚、7-甲氧基-2-甲基异黄酮、黄芩素、刺芒柄花素、柚皮素、β-谷甾醇、美迪紫檀素和甘草查尔酮A,核心靶点包括血管内皮生长因子A(VEGFA)、RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)、白细胞介素-6/8/10(IL-6/8/10)、肿瘤坏死因子(TNF)、前列腺素G/H合成酶2(PTGS2)、丝裂原活化蛋白激酶1/3/8(MAPK1/3/8)、信号转导与转录激活因子3(STAT3)、基质金属蛋白酶-2/9(MMP2/9)等,涉及白细胞介素17(IL-17)、丝裂原活化蛋白激酶(MAPK)、核因子-κB (NF-κB)、缺氧诱导因子-1(HIF-1)、环磷腺苷(cAMP)、Janus激酶/信号转导与转录激活子(JAK-STAT)、无翅型MMTV整合位点(Wnt)等Objective: To analyze the key active components and core targets of Xuanfei Dayu decoction in treating the recovery stage of COVID-19, and to explore the potential mechanism by network pharmacology and molecular docking technology.Methods: The property, taste, meridian tropism, active components and corresponding targets of 11 kinds of traditional Chinese medicine in Xuanfei Dayu decoction were obtained from Chinese pharmacopoeia, TCMSP and TCM@Taiwan database. The recovery stage of COVID-19 related diseases therapeutic targets were obtained from GeneCards and OMIM database. The potential targets of Xuanfei Dayu decoction in treating the recovery stage of COVID-19 were acquired by using Venny software to intersect the targets of traditional Chinese medicine and those of disease. The traditional Chinese medicine-property, taste, meridian tropism network and traditional Chinese medicine-active components-targets network were constructed by Cytoscape software, the PPI analysis of common targets was carried out by using STRING database. The key active components and core targets of Xuanfei Dayu decoction were screened based on the nodes attribute values. GO, KEGG signaling pathway and tissue expression enrichment analysis of common targets were performed by using Metascape and DAVID database. AutoDockTools software was used to analyze the affinity interactions between key active components and FGFR, VEGFR2.Results: Xuanfei Dayu decoction was flat and sweet in taste, and the meridian tropism was mainly in lung, spleen and heart. There were 137 active components and corresponding 231 targets in Xuanfei Dayu decoction related to the treatment of COVID-19 in recovery stage. The potential targets were mainly distributed in lung tissue. The key active components were quercetin, luteolin, kaempferol, 7-methoxy-2-methyl isoflavone, baicalein, formononetin, naringenin, β-sitosterol, medicarpin and licochalcone A. The core targets included VEGFA, AKT1, IL-6/8/10, TNF, PTGS2, MAPK1/3/8, STAT3 and MMP2/9, etc, and involved in I

关 键 词：宣肺达郁汤 新型冠状病毒肺炎 恢复期 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]