Department of Respiratory and Critical Care Medicine, Linping Campus, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Medicine (Baltimore). 2024 Aug 16;103(33):e39338. doi: 10.1097/MD.0000000000039338.
This study aimed to elucidate the molecular mechanisms underlying the therapeutic effects of Cangzhu Erchen decoction (CZECD) in the treatment of chronic obstructive pulmonary disease (COPD) using microarray analysis, network pharmacology, and molecular docking. The active components and candidate targets of CZECD were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Swiss Target Prediction. COPD-related targets were collected from 5 databases. Access to drug-disease interface targets in the Venny platform. The Cytoscape program and the STRING database were used for protein-protein interaction analysis and subsequent core target screening. The DAVID database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment pathway analysis, while AutoDockTools was used for molecular docking to confirm binding affinity between drugs and key targets. A total of 140 compounds from CZECD and 5100 COPD-related targets were identified. SRC, PIK3CA, STAT3, PIK3R1, AKT1, HSP90AA1, PIK3CB, GRB2, PIK3CD, and MAPK1 were identified as the major targets of CZECD in its anti-COPD activity. GO and Kyoto Encyclopedia of Genes and Genomes enrichment studies revealed that CZECD mainly affects biological processes such as protein phosphorylation, xenobiotic response, positive regulation of the MAPK cascade, and inflammatory responses. Cancer, PI3K/AKT, and MAPK were the key pathways mediating these effects. The positive association between the core targets and the compounds was further validated by molecular docking. CZECD exerts its therapeutic role in COPD mainly through multiple compounds, targets, and pathways.
本研究旨在通过基因芯片分析、网络药理学和分子对接技术，阐明苍术二陈汤（CZECD）治疗慢性阻塞性肺疾病（COPD）的作用机制。采用中药系统药理学数据库和分析平台（TCMSP）和瑞士靶向预测（Swiss Target Prediction）获取 CZECD 的活性成分和候选靶点，从 5 个数据库中收集 COPD 相关靶点，在 Venny 平台获取药物-疾病靶点交集。采用 Cytoscape 程序和 STRING 数据库进行蛋白质-蛋白质相互作用分析和核心靶点筛选，利用 DAVID 数据库进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，采用 AutoDockTools 进行分子对接，验证药物与关键靶点的结合亲和力。从 CZECD 中鉴定出 140 种化合物和 5100 个 COPD 相关靶点。SRC、PIK3CA、STAT3、PIK3R1、AKT1、HSP90AA1、PIK3CB、GRB2、PIK3CD 和 MAPK1 被确定为 CZECD 抗 COPD 活性的主要靶点。GO 和 KEGG 富集研究表明，CZECD 主要影响蛋白质磷酸化、异生物质反应、MAPK 级联的正向调节和炎症反应等生物过程。癌症、PI3K/AKT 和 MAPK 是介导这些作用的关键通路。通过分子对接进一步验证了核心靶点与化合物之间的正相关性。CZECD 主要通过多种化合物、靶点和通路发挥其在 COPD 中的治疗作用。
