基于网络药理学探讨巴蜀颗粒防治新型冠状病毒肺炎的潜在物质基础初探

Probing into the potential material basis of Bashu granules in preventing and treating novel coronavirus pneumonia based on network pharmacology

目的研究巴蜀颗粒抑制新型冠状病毒肺炎的潜在活性成分及作用机制。方法通过TCMSP和GeneCard等数据库对巴蜀颗粒中药材成分和靶点,新冠肺炎治疗相关靶点进行搜集;采用Cytoscape软件和String数据库对成分和靶点进行构建互作网络;对得到的核心靶点进行富集分析;用分子对接技术对3个核心成分与ACE2、3Clpro和PLpro进行分子对接;用巨噬细胞炎症模型实验对网络药理学分析结果进行验证。结果巴蜀颗粒-成分-靶点-疾病网络中包含101个成分,66个靶点;其中核心成分3个,核心靶点14个。GO富集分析得出2140个生理途径,其中2041个在生物过程上。KEGG富集得到148条相关信号通路。分子对接发现槲皮素、山奈酚、木犀草素等成分与3CLpro,ACE2,PLpro的结合能均低于-7.0 kcal/mol。验证实验结果表明,巴蜀颗粒可以降低LPS刺激所引起的iNOS蛋白增多和p65蛋白的磷酸化,且p-p65蛋白呈剂量依赖性降低。结论巴蜀颗粒主要通过槲皮素、山奈酚和木犀草素等黄酮类成分与ACE2、3Clpro和PLpro蛋白酶结合,抑制肺部炎症,发挥对新冠病毒肺炎起到防治作用。

Objective To study the potential active components and mechanism of action of Bashu granules in inhibiting COVID-19.Methods The TCMSP and GeneCard databases were used to collect the components and targets of Bashu granules,and the targets related to the treatment of COVID-19.Cytoscape software and String database was used to construct an interactions network for the components and targets.The core targets obtained were enriched and analyzed.Molecular docking technology was used to perform molecular docking of the three core components with ACE2,3Clproand Plpro,and the results of pharmacological analysis of network were validated by macrophage inflammation modeling experiments.Results The results showed that the drug-component-target-disease network contained 101 components and 66 targets.After theanalysis and screening,the final core components were three and the core targets were 14.GO enrichment analysis yielded 2140 physiological pathways,of which 2041 were on biological processes.KEGG was enriched to 148 related signal pathways.Molecular docking showed that the binding energies of quercetin,kaempferol,luteolin and other components with 3CLpro,ACE2 and PLpro were all lower than-7.0kcal/mol.The preliminary experimental results showed that Bashu granules could reduce the increase of iNOS protein and the phosphorylation of p65 protein induced by LPS stimulation,and p-p65 protein was decreased in a dose-dependent manner.Conclusion Through the combination of quercetin,kaempferol,luteolin and other components with 3CLpro,ACE2,and PLpro proteases,inhibition of lung inflammation,Ba Shu granule has a preventive and therapeutic effect on COVID-19 through the multiple signaling pathways.