Respiratory Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Respiratory Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Medicine (Baltimore). 2024 Nov 29;103(48):e40648. doi: 10.1097/MD.0000000000040648.
Network pharmacology and molecular docking methods were applied to elucidate the molecular mechanism of action of Wensan tincture (WST) in the treatment of pulmonary nodules. The Traditional Chinese Medicine Systems Pharmacology and the Traditional Chinese Medicine and Chemical Composition database were used to screen the active ingredients. Potential targets of WST were retrieved using Traditional Chinese Medicine Systems Pharmacology, SwissADME, and SwissTargetPrediction, while pulmonary nodule-associated targets were obtained from GeneCards and Online Mendelian Inheritance in Man databases. An active ingredient-target network was constructed using Cytoscape 3.9.1, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted via the Database for Annotation, Visualization, and Integrated Discovery platform to identify core targets and signaling pathways. Molecular docking studies were performed using AutoDockTools. The results revealed 62 active ingredients and 344 corresponding targets within the tincture, alongside 1005 targets associated with pulmonary nodules. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the potential therapeutic targets of WST include signal transducer and activator of transcription 3, mitogen-activated protein kinase-3, mitogen-activated protein kinase-1, Jun proto-oncogene, tumor protein 53, phosphoinositide-3-kinase regulatory subunit 1, heat shock protein 90 alpha family class A member 1, and AKT serine/threonine kinase 1. The primary pathways were the cancer pathway, mitogen-activated protein kinase signaling, advanced glycation end-products and their receptor signaling, epidermal growth factor receptor signaling, hypoxia-inducible factor-1 signaling, and the programmed cell death-ligand 1/programmed cell death protein 1 checkpoint pathways. Molecular docking demonstrated that quercetin exhibited the strongest binding affinity with mitogen-activated protein kinase-3, with a binding energy of -9.1 kcal/mol. Notably, key components of WST, such as quercetin, demonstrate considerable potential as drug candidates for the treatment of pulmonary nodules.
网络药理学和分子对接方法被应用于阐明温三酊（WST）治疗肺结节的作用机制。使用中药系统药理学数据库和中药化学成分数据库筛选 WST 的活性成分。使用中药系统药理学数据库、SwissADME 和 SwissTargetPrediction 检索 WST 的潜在靶点，同时从 GeneCards 和在线 Mendelian 遗传数据库中获取与肺结节相关的靶点。使用 Cytoscape 3.9.1 构建活性成分-靶标网络，通过数据库 for Annotation, Visualization, and Integrated Discovery 进行基因本体论和京都基因与基因组百科全书富集分析，以识别核心靶标和信号通路。使用 AutoDockTools 进行分子对接研究。结果显示，酊剂中含有 62 种活性成分和 344 个相应的靶标，与肺结节相关的靶标有 1005 个。基因本体论和京都基因与基因组百科全书富集分析表明，WST 的潜在治疗靶点包括信号转导和转录激活因子 3、丝裂原活化蛋白激酶-3、丝裂原活化蛋白激酶-1、原癌基因 Jun、肿瘤蛋白 53、磷酸肌醇-3-激酶调节亚基 1、热休克蛋白 90α 家族 A 成员 1 和 AKT 丝氨酸/苏氨酸激酶 1。主要通路包括癌症通路、丝裂原活化蛋白激酶信号通路、晚期糖基化终产物及其受体信号通路、表皮生长因子受体信号通路、缺氧诱导因子-1 信号通路和程序性细胞死亡配体 1/程序性细胞死亡蛋白 1 检查点通路。分子对接表明，槲皮素与丝裂原活化蛋白激酶-3 具有最强的结合亲和力，结合能为-9.1 kcal/mol。值得注意的是，WST 的关键成分，如槲皮素，显示出作为肺结节治疗药物候选物的巨大潜力。
