基于网络药理及分子对接探讨芪银三两三治疗特发性肺纤维化的作用机制

The Mechanism of Qiyin Sanliangsan(芪银三两三)in the Treatment of Idiopathic Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking

目的探讨验方芪银三两三治疗特发性肺纤维化(IPF)的可能机制。方法在TCMSP、GeneCards、NCBI、OMIM等数据库平台对芪银三两三组成药物的活性成分、作用靶点及IPF的疾病靶标进行检索筛选,将药物成分靶点与疾病靶标取交集,采用STRING数据库、Cytoscape 3.8.0软件及相关插件构建蛋白相互作用网络图(PPI),筛选关键成分,利用生物学信息注释数据库(DAVID)中对核心靶点进行基因本体(GO)富集分析、基因组百科全书(KEGG)通路富集分析。运用分子对接技术进行验证,进一步明确芪银三两三作用于IPF的核心靶点。结果共筛选获得芪银三两三药物活性成分147个,作用靶点664个,特发性肺纤维化相关基因1897个,将药物成分靶点与IPF疾病靶点取交集共获得靶点141个,构建PPI网络,经拓扑及聚类分析后获得STAT3、AKT1、JUN、IL6、MAPK3、SPP1、CASP8、IL1B、UGT1A1等关键靶点。GO分析显示,芪银三两三治疗IPF的作用机制涉及营养水平感应、氧化应激、化学应激、氧水平感知等过程。KEGG通路富集以病毒感染相关通路、炎症相关通路及其他疾病通路为主。分子对接结果显示,关键靶点STAT3、AKT1、JUN与活性成分槲皮素、木犀草素结合能≤-5.0Kcal/mol,显示较好的结合能力。结论结论芪银三两三可能通过作用于STAT3、AKT1、JUN、IL6等关键靶点,通过炎症反应、病毒感染以及与癌症等疾病相关的信号通路等实现对IPF的治疗作用。

Objective To explore the possible mechanism of the experienced formula Qiyin Sanliangsan(芪银三两三,QYSLS)in the treatment of idiopathic pulmonary fibrosis(IPF).Methods The TCMSP,GeneCards,NCBI,OMIM databases were searched for active components and action targets of QYSLS and disease targets of IPF;the drug component targets and disease targets were intersected;the STRING database,Cytoscape 3.8.0 software and related plug-ins were used to construct a protein protein interaction(PPI)network;key components were screened;the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to perform gene ontology(GO)enrichment analysis on core targets,and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis;the molecular docking technology was used to verify the core target of QYSLS on IPF.Results A total of 147 active components of QYSLS were screened,as well as 664 target points and 1897 IPF-related genes;141 targets obtained by intersecting drug component targets and IPF disease targets were used to construct a PPI network,and through topology and cluster analysis,STAT3,AKT1,JUN,IL6,MAPK3,SPP1,CASP8,IL1 B,UGT1 A1 and other key targets were gained.GO analysis showed that the action mechanism of QYSLS in the treatment of IPF was involved with the processes such as nutrient induction,oxidative stress,chemical stress,and oxygen perception.The KEGG enrichment pathway was dominated by viral infection-related pathways,inflammation-related pathways and other disease pathways.Molecular docking result showed that the blinding energy of key targets STAT3,AKT1,JUN with quercetin and luteolin was≤-5.0 Kcal/mol,suggesting good blinding ability.Conclusion The effects of QYSLS on IPF may relate to the action on key targets such as STAT3,AKT1,JUN,and IL6 by regulating signaling pathways related to inflammation,viral infection,cancer and other diseases.