基于网络药理学和分子对接技术探讨四磨汤治疗急性呼吸窘迫综合征的分子机制

Molecular Mechanism of Simo Decoction in the Treatment of Acute Respiratory Distress Syndrome Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学方法和分子对接技术分析四磨汤治疗急性呼吸窘迫综合征(ARDS)的活性成分及分子作用机制。方法:通过中药系统药理学数据库与分析平台获取木香、枳壳、乌药和槟榔的化学成分,根据阈值筛选活性成分及潜在靶点;利用GeneCards、DisGeNET数据库获取ARDS相关靶点,作韦恩图获取两者共有靶点;再构建共有靶点蛋白质-蛋白质相互作用网络,筛选出核心靶点进行富集分析。结果:四磨汤治疗ARDS的关键成分为槲皮素、蜜橘黄素、柚皮素和β-谷甾醇等,关键靶点有原癌基因蛋白(JUN)、丝裂原激活的蛋白激酶8(MAPK8)、原癌基因(FOS)、蛋白激酶B(AKT1)、胱天蛋白酶3(CASP3)和肿瘤坏死因子(TNF)等,涉及的生物学过程主要包括细胞化学应激的应答过程、活性氧的应答过程等,信号通路主要富集于流体剪切应力与动脉粥样硬化、TNF、MAPK以及白细胞介素17等信号通路。结论:本研究初步揭示了四磨汤治疗ARDS的多成分、多靶点、多通路的作用机制,为四磨汤的临床开发利用提供了基础。

OBJECTIVE:To analyze the the active components and molecular mechanism of Simo decoction in the treatment of acute respiratory distress syndrome(ARDS) based on network pharmacology and molecular docking.METHODS:The chemical components of Muxiang,Zhike,Wuyao and Binlang were obtained by TCMSP database,and the active components and potential targets were screened according to the threshold.GeneCards and DisGeNET databases were used to obtain ARDS-related targets,and the common targets were obtained by Venn diagram.Common target protein-protein interaction network was performed,and the core target was selected for enrichment analysis.RESULTS:The key components of Simo decoction in the treatment of ARDS were quercetin,nobiletin,naringenin and β-sitosterol.The key targets were JUN,mitogen-activated protein kinases-8(MAPK8),proto-oncogenes(FOS),protein kinase B(AKT1),caspases3(CASP3),tumor necrosis factor(TNF).The biological processes mainly included the response to cytochemical stress and response to reactive oxygen species.Signaling pathways were mainly enriched in fluid shear stress and atherosclerosis,TNF,MAPK and Interleukin 17 signaling pathways.CONCLUSIONS:This study preliminarily reveals the multi-component,multi-target and multi-pathway mechanism of Simo decoction in the treatment of ARDS,which provides basis for the clinical development and utilization of Simo decoction.