基于网络药理学探讨三拗汤治疗咳嗽变异型哮喘的作用机制

Mechanism of San’ao Decoction in treatment of cough variant asthma on the basis of network pharmacology

目的根据网络药理学方法对三拗汤治疗咳嗽变异型哮喘的作用机制进行探讨。方法利用中药系统药理学数据库与分析平台(TCMSP)对三拗汤中有效成分进行筛选及靶点预测,检索GeneCards、OMIM数据库筛选CVA疾病靶点,借助网络拓扑分析插件CytoNCA筛选三拗汤治疗CVA核心靶点,使用Cytoscape 3.7.1建立化合物-疾病-靶点调控网络,基于DAVID数据库对核心靶点进行GO功能富集和KEGG通路富集分析。结果基于TCMSP得到三拗汤的114个有效成分和254个潜在靶点,筛选获得与CVA疾病发生、发展相关的靶点2 257个,借助网络拓扑分析插件CytoNCA筛选得到三拗汤治疗CVA的核心靶点28个,GO功能富集分析得到条目328个,其中生物过程条目264个、分子功能条目46个、细胞组成条目18个,主要包括细胞凋亡、脂多糖反应、丝裂原活化蛋白激酶(MAPK)活性、一氧化氮合酶活性等功能途径;KEGG通路富集分析得出条目115个,主要包括MAPK信号通路、肿瘤坏死因子信号通路、Th17细胞分化等通路途径。结论基于网络药理学初步探讨并验证了三拗汤治疗CVA多成分、多靶点、多通路的整体调节作用特点,预测了三拗汤治疗CVA的潜在作用机制,以期为其活性成分研究与实验研究提供科学依据。

Objective To explore the mechanism of San’ao Decoction in the treatment of cough variant asthma(CVA).Methods The TCMSP database was used to screen the effective components and predict the target of San’ao Decoction.GeneCards and OMIM database were searched to screen the CVA disease target.CytoNCA was used to screen the core target of San’ao Decoction in the treatment of CVA.Cytoscape 3.7.1 was used to establish a compound disease target regulatory network.On the basis of DAVID database,GO and KEGG pathway enrichment analyses were conducted to determine the core targets of San’ao Decoction.Results On the basis of TCMSP,114 effective components and 254 potential targets of San’ao Decoction were obtained.A total of 2257 targets related to the occurrence and development of CVA were screened.Twenty-eight core targets of San’ao Decoction for CVA treatment were screened by using the network topology analysis plug-in CytoNCA.Total 328 entries were obtained by GO function enrichment analysis,including 264 entries of biological process and 46 entries of molecular function and 18 orders of cell composition,mainly including apoptosis,lipopolysaccharide reaction,mitogen activated protein kinase(MAPK)activity,nitric oxide synthetase activity and other functional pathways.A total of 115 entries were obtained from KEGG pathway enrichment analysis,mainly including MAPK signalling pathway,tumour necrosis factor signalling pathway,Th17 cell differentiation and other pathways.Conclusion On the basis of network pharmacology,the overall regulatory characteristics of San’ao Decoction in the treatment of CVA,including multi-component,multi-target and multi-channel,are preliminarily discussed and verified,and the potential mechanism of San’ao Decoction in the treatment of CVA is predicted so as to provide scientific basis for the research of its active components.