摘要
目的运用网络药理学与分子对接方法分析肺维康颗粒治疗COVID-19相关肺纤维化(COVID-19-PF)的关键成分和潜在靶点,并探讨其可能的作用机制。方法在中药系统药理学分析平台(TCMSP)获得肺维康颗粒所含活性成分与相关靶点,通过OMIM和Genecards数据库收集COVID-19-PF相关基因,取交集后采用Cytoscape软件建立"肺维康颗粒-化合物-靶点-COVID-19-PF"网络模型;通过STRING、Metascape平台分析药物-疾病靶点蛋白相互作用,并进行网络构建和模块分析;对靶点进行GO分析和KEGG通路富集分析,对关键靶点进行核心化合物分子对接。结果肺维康颗粒治疗COVID-19-PF的关键靶点涉及蛋白激酶B1(AKT1)、血管内皮生长因子A(VEGFA)、白细胞介素6(IL-6)等,靶点基因功能倾向于调控细胞因子受体、影响细胞因子分泌水平和G蛋白偶联胺受体活性、激活细胞转录因子等;关键的KEGG通路包括白细胞介素17(IL-17)信号通路、肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路等,其中薯蓣皂苷元、二氢丹参酮Ⅰ、木犀草素可与血管紧张素转化酶2(ACE2)、血管内皮生长因子受体(VEGFR)、AKT1等关键靶点形成稳定构象。结论肺维康颗粒可能通过调控PI3K/AKT等炎症和纤维化相关通路、抑制细胞因子活化和血管生成、减轻胶原沉积和肺组织结构重塑等机制发挥对COVID-19-PF的治疗作用。
Objective Network pharmacology and molecular docking were used to predict the key components and potential targets of Feiweikang granules in the treatment of COVID-19-related pulmonary fibrosis(COVID-19-PF),and to explore the molecular basis and mechanism of action.Methods The active components and related targets of Feiweikang granules were obtained from TCMSP.The COVID-19-PF-related genes were collected through OMIM and Genecards databases.After the intersection,the network model of"Feiweikang granules compound targeting COVID-19-PF"was established by using the software of Cytoscape.The drug-disease target protein-protein interaction was analyzed by using STRING and Metascape platform as well as the network construction and module analysis;gene function(GO)analysis and Kyoto Encyclopedia of genes and genomes(KEGG)were performed on target genes,and we docked the core compounds with key targets.Results The key targets of Feiweikang granules in the treatment of COVID-19-PF were protein kinase B1(AKT1),vascular endothelial growth factor A(VEGFA),interleukin-6(IL-6),etc.;the function of target gene tended to regulate cytokine receptor,affect cytokine secretion level,G protein coupled amine receptor activity,and activate cell transcription factor,etc.;the key KEGG pathway included interleukin-17(IL-17)signal pathway,tumor necrosis factor(TNF)signal pathway,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signal pathway,etc;among them,diosgenin,dihydrotanshinone I,and luteolin could form stable conformation with ACE2,VEGFR,AKT1 and other key targets.Conclusion Feiweikang granules may play a role in the treatment of COVID-19-PF by regulating PI3K/AKT and other inflammatory and fibrosis-related pathways,inhibiting cytokine activation and angiogenesis,and reducing collagen deposition and lung tissue remodeling.
作者
杨帆
李宛洋
曹仁爽
毕张扬
张伟
YANG Fan;LI Wanyang;CAO Renshuang;BI Zhangyang;ZHANG Wei(Shandong University of Traditional Chinese Medicine,Jinan 250014,China;不详)
出处
《山东医药》
CAS
2020年第23期6-10,共5页
Shandong Medical Journal
基金
山东省重大科技创新工程(2020SFXGY04-1)
泰山学者建设工程(201712096)。
