基于网络药理学探讨麻黄定喘汤治疗哮喘的作用机制  

Network Pharmacology Approach to Explore Mechanisms of Mahuang Dingchuan Decoction for Treatment of Asthma

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作  者:张骞 张欣月 李江娅 梁丽菊 林浩畅 翁稚颖 

机构地区:[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南 昆明

出  处:《中医学》2021年第6期748-761,共14页Traditional Chinese Medicine

摘  要:目的:基于网络药理学方法分析麻黄定喘汤治疗哮喘的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)获取麻黄定喘汤中各药的主要化学成分与其靶点,依据ADME对活性组分进行筛选;通过Genecards,OMIM,DRUGBANK数据库获取哮喘主要靶点,两者取交集后通过String平台对交集靶点进行蛋白质相互作用分析,构建PPI网络并采用Cytoscape3.7.2软件对PPI网络中蛋白质功能模块进行挖掘。通过Metascape平台对交集靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:从麻黄定喘汤中共得到化学成分188个,共涉及靶点247个,与哮喘相关的基因1051个,二者取交集后获得120个麻黄定喘汤治疗哮喘的靶标,包括信号转导和转录激活因子3 (STAT3)、毒蕈碱型乙酰胆碱受体M3 (CHRM3),α2A肾上腺素能受体(ADRA2A),μ阿片受体(OPRM1),趋化因子10 (CXCL10),趋化因子8 (CXCL8),分裂原活化蛋白激酶1 (MAPK1),肿瘤坏死因子(TNF)等核心靶点,GO富集分析与KEGG通路富集分析显示麻黄定喘汤可以影响细胞对毒性物质的反应,调控MAPK级联反应,调节糖尿病并发症中的AGE-RAGE信号通路,TNF信号通路,NF-κB信号通路等通路。结论:该研究预测了麻黄定喘汤治疗哮喘的潜在作用机制,初步揭示了麻黄定喘汤多成分、多靶点、多通路的作用特点。Objective: To explore the mechanisms of Mahuang Dingchuan Decoction in the treatment of asthma based on network pharmacology. Methods: Active ingredients and targets of Mahuang Dingchuan Decoction were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), screening of active ingredients based on ADME;tar-gets of asthma were retrieved from Genecards, OMIM, DRUGBANK database, after the intersec-tion of the two, the protein interaction analysis was performed on the intersection through String datebase, a protein interaction network was constructed and Cytoscape3.7.2 wad used to mine protein functional modules in the network. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were per-formed on the Metascape platform. Result: A total of 188 chemical components were obtained from Mahuang Dingchuan Decoction, involving 247 targets, and 1051 targets related to asthma, after the intersection,120 targets of Mahuang Dingchuan Decoction were determined to treat asthma, including Signal transducer and activator of transcription 3 (STAT3), Muscarinic ace-tylcholine receptor M3 (CHRM3), Alpha-2A adrenergic receptor (ADRA2A), Mu-type opioid re-ceptor (OPRM1), C-X-C motif chemokine 10 (CXCL10), Interleukin-8 (CXCL8), Mitogen-activated protein kinase 1 (MAPK1), Tumor necrosis factor (TNF) and other core targets. GO analysis and KEGG analysis prove that Mahuang Dingchuan Decoction can affect cellular response to toxic substance, regulation of MAPK cascade and regulate AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, NF-kappa B signaling pathway and other pathway. Con-clusion: The study predicted the potential mechanisms of Mahuang Dingchuan Decoction in the treatment of asthma, and initially revealed the multi-component, multi-target, multi-pathway characteristics of Mahuang Dingchuan Decoction.

关 键 词:网络药理学 麻黄定喘汤 哮喘 机制 

分 类 号:R28[医药卫生—中药学]

 

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