当归平喘复方的优选及其治疗支气管哮喘的作用机制分析

Screening of the optimal compound formula of Angelica sinensis to treat asthma and analysis of its mechanism of action

目的优选当归平喘复方并分析复方治疗支气管哮喘的作用机制。方法检索中国知网(CNKI)全文数据库,收集临床及名中医治疗支气管哮喘的当归复方,对当归复方所涉及中药的频次、性味归经及功效进行统计分析,对频次较高的中药进行关联规则分析,从而筛选当归治疗支气管哮喘的优选复方。利用中药系统药理学数据库(TCMSP)、PubChem及Swiss Target Prediction数据库查询当归优选复方活性成分及对应靶点,采用DisGeNet、在线人类孟德尔遗传(OMIM)及美国国家生物技术信息中心(NCBI)数据库筛选支气管哮喘相关靶点,将二者靶点匹配映射得到当归优选复方治疗支气管哮喘的关键靶点,对关键靶点进行蛋白质-蛋白质相互作用(PPI)网络、基因本体(GO)功能与京都基因与基因组百科全书(KEGG)信号通路分析,利用Cytoscape 3.7.1软件构建中药-关键成分-关键靶点与通路-关键靶点网络,并借助Network Analyzer计算网络拓扑参数。结果CNKI数据库近15年临床治疗支气管哮喘的复方共计578首,涉及中药302味,其中以补虚药、化痰止咳平喘药最为常见,归经以肺、脾、肝多见,性味以温、寒、甘、辛居多,关联规则分析得到治疗支气管哮喘的当归优选复方为金水六君煎。生物信息学分析发现,当归优选复方金水六君煎通过槲皮素、丁苯酞及山奈酚等成分作用于白细胞介素-6(IL-6)、血管内皮生长因子A(VEGFA)及丝裂原活化蛋白激酶3(MAPK3)等靶点从而调控肿瘤坏死因子(TNF)、白细胞介素-17(IL-17)及缺氧诱导因子1(HIF-1)等信号通路发挥平喘的作用。结论当归治疗支气管哮喘的优选复方为金水六君煎,金水六君煎通过“多成分-多靶点-多通路”发挥治疗哮喘的作用。

Objective To screen the optimal Angelica sinensis compound for treating bronchial asthma and analyze its mechanism of action in treating bronchial asthma.Methods Retrieve the full text database of China National Knowledge Infrastructure(CNKI),collect clinical and famous traditional Chinese medicine prescriptions treating bronchial asthma,conduct statistical analysis on the frequency,nature,taste,meridian distribution,and efficacy of traditional Chinese medicine prescriptions involved,and conduct association rule analysis on higher frequency traditional Chinese medicine prescriptions to screen the optimal prescription for treating bronchial asthma.Using the Traditional Chinese Medicine System Pharmacology Database(TCMSP),PubChem,and Swiss Target Prediction databases to search for the active ingredients and corresponding targets of Angelica sinensis optimal compound,DisGeNet,online Mendelian Inheritance in Man(OMIM),and the National Center for Biotechnology Information(NCBI)databases to screen for bronchial asthma related targets,matching and mapping the two targets to obtain the key targets of Angelica sinensis optimal compound for treating bronchial asthma,Perform protein protein interaction(PPI)network,gene ontology(GO)function,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway analysis on key targets,use Cytoscape 3.7.1 software to construct a traditional Chinese medicine-key component-key target and pathway-key target network,and use Network Analyzer to calculate network topology parameters.Results In the past 15 years,there have been a total of 578 clinical for treating bronchial asthma in the CNKI database,involving 302 traditional Chinese medicine ingredients.Among them,tonifying deficiency drugs and phlegm resolving cough relieving and asthma relieving drugs are the most common,with the meridians of the lungs,spleen,and liver being the most common,and the nature and taste being mainly warm,cold,sweet,and spicy.Analysis of association rules showed that the optimal prescription for treating bronchial asthma in Angelica sinensis is Jinshui Liujun Decoction(金水六君煎).Bioinformatics analysis found that the optimized compound of Angelica sinensis,Jinshui Liujun Decoction,exerts its antiasthmatic effect by acting on targets such as interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),and mitogen activated protein kinase3(MAPK3)through components such as quercetin,butylphthalide,and kaempferol,regulating tumor necrosis factor(TNF),interleukin-17(IL-17),and hypoxia inducible factor 1(HIF-1)signaling pathways.Conclusion The optimal formula for treating bronchial asthma with Angelica sinensis is Jinshui Liujun Decoction,which exerts its therapeutic through"multi-component,multi-target,multi-pathway".