基于整合药理学及分子对接技术探讨小青龙汤治疗慢性阻塞性肺疾病急性加重期的分子机制

Discussion on the molecular mechanism of Xiaoqinglong Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease based on integrative pharmacology and molecular docking technology

目的借助整合药理学与分子对接技术探讨小青龙汤治疗慢性阻塞性肺疾病急性加重期(AECOPD)的分子机制。方法通过中医药整合药理学平台V2.0检索小青龙汤的药物成分和靶标,运用GeneCards、OMIM数据库查找疾病靶标,运用STRING数据库构建蛋白质-蛋白质相互作用网络,运用Cytoscape 3.7.2构建“方剂-活性成分-核心靶标-表型-疾病”多维网络图。运用AutoDock软件对活性成分与核心靶标进行分子对接。结果获得小青龙汤治疗AECOPD的潜在活性成分41个,核心靶标23个。基因本体和京都基因和基因组数据库富集分析显示,核心靶标多参与炎症免疫、氧化应激、能量代谢等生物学过程。分子对接显示芍药二酮、异甘草素、2,4,4’-三羟基查耳酮与表皮生长因子、Akt激酶1、肿瘤坏死因子具有较高亲和力。结论初步筛选出小青龙汤治疗AECOPD的潜在活性成分及作用靶标,其多成分、多靶点作用主要通过炎症免疫、氧化应激及能量代谢等生物过程改善AECOPD进程。

Objective To explore the molecular mechanism of Xiaoqinglong Decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)by integrating pharmacology and molecular docking technology.Methods Components and targets of Xiaoqinglong Decoction were retrieved by integrative pharmacology-based research platform of traditional Chinese medicine V2.0 database,and the targets related to AECOPD were queried by using GeneCards and OMIM databases.Protein-protein interaction network was performed by using STRING database.The multidimensional network diagram of“prescription-active ingredient-core target-phenotype-disease”was constructed by using Cytoscape 3.7.2 software.The active ingredients and the core targets were performed to molecular docking by using AutoDock software.Results A total of 41 components and 23 core targets of Xiaoqinglong Decoction were retrieved.Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis indicated that core targets were mostly involved in biological processes such as inflammation and immunity,oxidative stress,and energy metabolism.Molecular docking showed that paeoniflorin dione,isoglycyrrhizin,and 2,4,4’-trihydroxychalcone had high affinity with epidermal growth factor,Akt kinase 1,and tumor necrosis factor.Conclusion The potential active components and targets of Xiaoqinglong Decoction in the treatment of AECOPD are initially screened,its multi-component and multi-target effects mainly improve AECOPD process through biological processes such as inflammation and immunity,oxidative stress,and energy metabolism.