基于网络药理学及分子对接探讨经方华盖散治疗支气管哮喘的作用机制研究OA
Mechanistic study of Hua Gai San in the treatment of bronchial asthma based on network pharmacology and molecular docking
目的:基于网络药理学及分子对接探讨经方华盖散治疗支气管哮喘(简称哮喘)的作用机制.方法:选用中药系统药理学数据库与分析平台和本草组鉴(HERB)数据库获取华盖散的活性成分及靶点,用 GeneCards、OMIM、TTD 和PharmGKB 数据库获取哮喘的相关靶点,用 Veeny 平台对华盖散的活性成分作用靶点与哮喘的相关靶点取交集,得到共同靶点.借助Cytoscape 3.9.1建立"药物-成分-靶点-疾病"相互作用网络.将交集靶点导入STRING 数据库,进行交集靶点相互作用分析,构建交集靶点蛋白质-蛋白质相互作用网络.采用Cytoscape内的CytoNCA插件和CytoHubba插件筛选出核心靶点及网络,通过 DAVID 平台进行基因本体论(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.借助 Cytoscape 3.9.1 建立"药方-通路-靶点-疾病"相互作用网络.用 AutoDock Vina 进行分子对接并用 ChimeraX 进行可视化.结果:共得到华盖散靶点 352 个,哮喘靶点 2 303 个,两者取交集后共得到 196 个靶点.通过蛋白质-蛋白质相互网络筛选出核心靶点肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素(interleukin,IL)-6、基质金属蛋白酶(matrix metalloproteinase,MMP)9、信号转导和转录活化因子(signal transducer and activator of transcription,STAT)3、丝氨酸/苏氨酸蛋白激酶 1(Akt serine-threonine protein kinase 1,AKT1)等.通过 GO 功能富集分析得到 326 条生物过程、21 条细胞组成、45 条分子功能.通过KEGG通路富集分析获得135条通路,主要包括IL-17信号通路、Janus激酶(janus kinase,JAK)-信号转导和转录活化因子(signal transducer and activator of transcription,STAT)信号通路、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、Toll 样信号通路等.分子对接结果显示,结合能多为-5.0 kcal/mol(1 kcal/mol ≈4.18 kJ/mol)以下,关键活性成分与目标靶点结合力较稳定.结论:华盖散可能通过调节槲皮素、山柰酚、β-谷甾醇、木犀草素、柚皮素等成分,作用于 TNF、IL-6、MMP9 等靶点,调节IL-17 信号通路、JAK-STAT 信号通路等,从而起到治疗哮喘的作用.本研究结果为进一步探究经方华盖散治疗哮喘的有效成分及药理作用机制提供了更多依据.
Objective:To investigate the therapeutic mechanism of the classic formula Huagai San(华盖散)in treating bronchial asthma through network pharmacology and molecular docking.Methods:Active components and targets of Huagai San were identified using TCMSP and HERB databases.Bronchial asthma-related targets were obtained from GeneCards,OMIM,TTD,and PharmGKB databases.Venn diagrams were employed to identify overlapping targets between Huagai San's active components and asthma-related targets.A"drug-component-target-disease"interaction network was constructed using Cytoscape 3.9.1.Overlapping targets were imported into the STRING database for protein-protein interaction(PPI)network analysis.Core targets and networks were analyzed and screened using CytoNCA and CytoHubba plugins in Cytoscape.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using the David platform.A"prescription-pathway-target-disease"interaction network was established in Cytoscape 3.9.1.Molecular docking was conducted using AutoDock Vina,with visualization performed via ChimeraX.Results:The study identified 352 potential targets of Huagai San and 2 303 asthma-related targets,with 196 overlapping targets identified through intersection analysis.PPI network screening revealed core targets including TNF,IL-6,MMP9,STAT3,and AKT1.GO functional enrichment analysis identified 326 biological processes,21 cellular components,and 45 molecular functions.KEGG pathway enrichment analysis identified 135 pathways,primarily involving IL-17 signaling,JAK-STAT signaling,MAPK signaling,and Toll-like signaling.Molecular docking results showed binding energies predominantly below-5.0 kcal/mol(1 kcal/mol≈4.18 kJ/mol),indicating stable interactions between key active components and core targets.Conclusion:Huagai San may exert therapeutic effects on bronchial asthma by regulating targets such as TNF,IL-6,and MMP9 through components including quercetin,kaempferol,β-sitosterol,luteolin,and hesperidin,while modulating IL-17 signaling and JAK-STAT signaling pathways.These findings provide scientific evidence for further investigation into the active components and pharmacological mechanisms of this classical Chinese medicine in asthma treatment.
崔新蕊;金子涵;李一帆;刘伟
天津中医药大学研究生院,天津,301617天津中医药大学研究生院,天津,301617天津中医药大学研究生院,天津,301617天津中医药大学第二附属医院,天津,300250
医药卫生
华盖散支气管哮喘网络药理学分子对接
Huagai SanBronchial asthmaNetwork pharmacologyMolecular docking
《中医临床研究》 2026 (5)
39-50,12
海河实验室科研项目(LW20250102)天津中医药大学第二附属医院薪火相传骨干人才(津中医二附政发[2023]50号).
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