基于网络药理学和分子对接方法探究铁皮石斛治疗慢性萎缩性胃炎的作用机制

Mechanism of Dendrobium officinale in treatment of chronic atrophic gastritis based on network pharmacology and molecular docking method

目的通过网络药理学方法和分子对接技术对铁皮石斛治疗慢性萎缩性胃炎的潜在作用机制进行探讨。方法基于CNKI和PubMed数据库筛选出铁皮石斛的有效成分,通过Swiss Target Prediction数据库对活性成分靶点进行预测,运用Cytoscape软件构建“有效成分–靶点”网络。通过GeneCards和OMIM数据库收集疾病靶点并与药物靶点相交集,得出铁皮石斛治疗慢性萎缩性胃炎的有效靶点。通过STRING数据库进行蛋白互相作用(PPI)分析、Metascape数据库进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路分析、AutoDockVina软件进行分子对接验证。结果通过筛选得出铁皮石斛的有效成分有14种,靶点188个,疾病靶点有768个。铁皮石斛治疗慢性萎缩性胃炎的有效靶点为38个。PPI分析得出铁皮石斛作用于AKT1、EGFR、MAPK3、PTGS2、MMP-9、SRC、HSP90AA1等核心靶点对慢性萎缩性胃炎发挥作用。GO分析及KEGG通路分析筛选出细胞外基质、蛋白激酶活性、对氧化应激的反应等生物学功能和IL-17、癌症的途径、细胞凋亡、钙信号等10条通路与之密切相关。分子对接结果验证了有效成分和关键靶点的相互作用,其中柚皮素、槲皮素与核心靶点MMP-9的对接亲和度较高。结论通过网络药理学证明了铁皮石斛主要通过多靶点、多通路和多途径对慢性萎缩性胃炎发挥其治疗作用,为治疗慢性萎缩性胃炎提供新的方向和依据。

Objective The potential mechanism of Dendrobium officinale in treatment of chronic atrophic gastritis was discussed by network pharmacological methods and molecular docking technology.Methods The active components of Dendrobium officinale were screened based on CNKI and PubMed databases,and their targets were predicted through Swiss Target Prediction database.The“active component–target”network was constructed by Cytoscape software.Disease targets were collected through GeneCards and OMIM databases,and intersected with drug targets to obtain the effective targets of Dendrobium officinale in treatment of chronic atrophic gastritis.PPI analysis was carried out through String database,GO analysis and KEGG pathway analysis were carried out through Metascape database,and molecular docking verification was carried out by AutoDockVina software.Results The results showed that there were 14 effective components,188 targets,and 768 disease targets of Dendrobium officinale,and 38 effective targets of Dendrobium officinale in treatment of chronic atrophic gastritis.PPI analysis showed that Dendrobium officinale acted on AKT1,EGFR,MAPK3,PTGS2,MMP-9,SRC,HSP90AA1 and other core targets,and played a role in chronic atrophic gastritis.GO analysis and KEGG pathway analysis showed that the biological functions such as extracellular matrix,protein kinase activity,and response to oxidative stress were closely related to IL-17,cancer pathway,apoptosis,and calcium signal.The molecular docking results verified the interaction between the active ingredient and the core target.The docking affinity between naringin,quercetin and the core target MMP-9 was the highest.Conclusion Through the scientific nature of network pharmacology,this study proved that Dendrobium officinale mainly plays its therapeutic role in chronic atrophic gastritis through multi-target,multi-channel and multi-channel,and provides a new direction and basis for the treatment of chronic atrophic gastritis.