苏挺丸治疗哮喘的分子机制：基于网络药理学和分子对接的研究
Molecular mechanisms of the Suting Pill in the treatment of asthma: A study based on network pharmacology and molecular docking.
作者信息
Wang Wei, Gong Leilei, Zhong Shujian, Ling Jing
机构信息
Department of Pharmacy, The Third Department, Air Force Special Service Sanatorium, Hangzhou, Zhejiang, China.
Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
出版信息
Medicine (Baltimore). 2025 Sep 5;104(36):e44243. doi: 10.1097/MD.0000000000044243.
BACKGROUND
Asthma is a chronic respiratory disease characterized by complex etiology and marked heterogeneity. It is one of the most prevalent chronic airway conditions in children, with increasing prevalence in recent years. The Suting Pill (STP), a traditional Chinese medicine for childhood asthma, has an unclear mechanism. This study aimed to investigate the key chemical constituents and potential mechanisms of STP in asthma treatment using network pharmacology and molecular docking.
METHODS
The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Integrated Pharmacology Research Platform (TCMIP) databases were used to identify STP ingredients and their targets. Asthma-related targets were identified from Online Mendelian Inheritance in Man (OMIM), GeneCards, DrugBank, Therapeutic Target Database (TTD), and PharmGKB databases. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Molecular docking was employed to assess binding affinities between targets and compounds.
RESULTS
A total of 22 potential active ingredients, 221 drug-related targets, and 420 asthma-related targets were identified, with 53 common targets. PPI network analysis identified TNF, IL-6, MMP-9, IL-4, and others as the core targets of STP's asthma treatment. Bioinformatics enrichment analysis indicated that these shared targets primarily act on signaling pathways such as the AGE-RAGE signaling pathway in diabetic complications, Chagas disease, fluid shear stress and atherosclerosis, the TNF signaling pathway, and lipid and atherosclerosis. Molecular docking revealed that kaempferol, luteolin, and quercetin had high binding activity with IL-6, IL-4, CCL2, TNF, MMP-9, and TGFB1. The combination of MMP9 and luteolin exhibited the strongest binding with an energy of - 10.4 kcal/mol, outperforming MMP9-quercetin (-9.9 kcal/mol) and TNF-kaempferol (-9.4 kcal/mol) binding.
CONCLUSION
We identified the bioactive components of STP and their potential targets in asthma treatment.
背景
哮喘是一种慢性呼吸道疾病，病因复杂，具有显著的异质性。它是儿童中最常见的慢性气道疾病之一，近年来患病率呈上升趋势。苏葶丸（STP）是一种用于治疗儿童哮喘的中药，其作用机制尚不清楚。本研究旨在利用网络药理学和分子对接技术，探讨STP治疗哮喘的关键化学成分和潜在机制。
方法
利用中药系统药理学数据库（TCMSP）和中药综合药理学研究平台（TCMIP）数据库，确定STP的成分及其靶点。从人类孟德尔遗传在线数据库（OMIM）、基因卡片数据库（GeneCards）、药物银行数据库（DrugBank）、治疗靶点数据库（TTD）和药物基因组知识库（PharmGKB）中识别哮喘相关靶点。使用搜索相互作用基因/蛋白质的工具（STRING）数据库构建蛋白质-蛋白质相互作用（PPI）网络。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。采用分子对接技术评估靶点与化合物之间的结合亲和力。
结果
共鉴定出22种潜在活性成分、221个药物相关靶点和420个哮喘相关靶点，其中有53个共同靶点。PPI网络分析确定肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、基质金属蛋白酶-9（MMP-9）、白细胞介素-4（IL-4）等为STP治疗哮喘的核心靶点。生物信息学富集分析表明，这些共同靶点主要作用于糖尿病并发症中的晚期糖基化终末产物受体（AGE-RAGE）信号通路、恰加斯病、流体切应力与动脉粥样硬化、TNF信号通路以及脂质与动脉粥样硬化等信号通路。分子对接显示，山奈酚、木犀草素和槲皮素与IL-6、IL-4、趋化因子配体2（CCL2）、TNF、MMP-9和转化生长因子β1（TGFB1）具有较高的结合活性。MMP9与木犀草素的组合表现出最强的结合，能量为-10.4千卡/摩尔，优于MMP9-槲皮素（-9.9千卡/摩尔）和TNF-山奈酚（-9.4千卡/摩尔）的结合。
结论
我们确定了STP的生物活性成分及其在哮喘治疗中的潜在靶点。
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