润肺宁神方治疗新型冠状病毒肺炎致失眠的网络药理学机制

Network pharmacological mechanism of Runfei Ningshen Decoction in the treatment of insomnia caused by COVID-19

目的用网络药理学和分子对接方法研究润肺宁神方治疗新型冠状病毒肺炎(COVID-19)致失眠的机制。方法在TCMSP、Batman和CTD数据库查找润肺宁神方中药材的化学成分和靶点;在Disgenet、GeneCards、CTD和Malacards数据库中查找COVID-19和失眠的相关靶点;用Cytoscape 3.2.1软件构建成分-靶点-疾病网络;在String数据库构建PPI网络;用R语言软件平台中Cluster Profiler软件包将共同靶点进行通路富集。用Discovery Studio 4.0软件对COVID-19致失眠相关的核心靶点进行分子对接。结果搜集到润肺宁神方药材成分349个,靶点1904个,COVID-19相关靶点1505个,失眠相关靶点1337个;韦恩图取交集得到2个疾病共同靶点404个,药材与2个疾病交集靶点250个,靶点间相互作用网络构建分析筛选出核心靶点33个。通路富集分析显示,润肺宁神方治疗失眠主要作用于AKT1、INS、TP53、IL-6、JUN、CASP3、TNF、CAT、PTGS2和CXCL8等关键靶点,参与人类巨细胞病毒感染、流体剪切应力与动脉粥样硬化和糖尿病并发症中的AGE-RAGE信号通路等重要通路过程。分子对接结果表明,核心靶点与β-谷甾醇、1-甲氧基菜豆素、3′-羟基-4′-O-甲基光甘草定与脱水淫羊藿素的亲和力较高。处方治疗COVID-19致失眠可能是通过PTGS2、AR、PPARG、NOS2和HSP90AA1等靶点发挥作用。结论推测润肺宁神方通过抑制IL-6、TNF-α等途径发挥治疗COVID-19致失眠的作用。

Objective To study the mechanism of Runfei Ningshen Decoction in the treatment of insomnia caused by corona virus disease 2019(COVID-19)by using network pharmacology and molecular docking analysis.Methods The chemical components and targets of Chinese medicinal materials of Runfei Ningshen Decoction in TCMSP,Batman,and CTD databases were searched.The relevant targets of novel coronavirus pneumonia and insomnia in Disgenet,GeneCards,CTD,and Malacards databases were searched.The component-target-disease network was established by using Cytoscape 3.2.1 software;The protein-protein intereation(PPI)network was constructed in string database.The common targets were enriched by using Cluster Profiler software package in R language software platform.The molecular docking of core targets related to insomnia caused by COVID-19 was carried out by using Discovery Studio 4.0 software.Results 349 medicinal ingredients in Runfei Ningshen Decoction,1904 targets,1505 new coronavirus pneumonia-related targets,and 1337 insomnia-related targets were collected.When the intersection of Venn diagrams were used,404 common targets were obtained for the 2 diseases.250 targets were intersected with the 2 diseases,and 33 core targets were screened out by the analysis of the interaction network between targets.Pathway enrichment analysis showed that Runfei Ningshen Decoction mainly acts on AKT1,INS,TP53,IL-6,key targets such as AKT1,INS,TP53,IL-6,JUN,CASP3,TNF,CAT,PTGS2 and CXCL8,which are involved in the important pathway processes such as human cytomegalovirus infection,fluid shear stress,and AGE-RAGE signaling pathways in complications of atherosclerosis and diabetes.The results of molecular docking showed that the core target has a high affinity withβ-sitosterol,1-methoxy phaseolin,3′-hydroxy-4′-O-methylglycyrrhizin,and anhydroicariin.The prescription treatment of insomnia caused by COVID-19 may be through the targets such as PTGS2,AR,PPARG,NOS2,HSP90AA1 and so on.Conclusion Runfei Ningshen Decoction can treat insomnia caused by COVID-19 by inhibiting IL-6 and TNF-α.