基于嗅觉受体的辛香类中药陈皮、丁香和小茴香药性表达的网络药理学研究

Study on herb property expression of pungent-aromatic Citri Reticulatae Pericarpium, Caryophylli Flos, and Foeniculi Fructus based on network pharmacology of olfactory receptors

目的采用网络药理学技术和方法,筛选辛香类中药陈皮、丁香、小茴香和嗅觉受体相互作用的物质基础、靶点和通路,揭示辛香类中药辛味药性表达的分子机制。方法通过TCMSP等数据库收集陈皮、丁香、小茴香3味辛香类中药的化学成分,筛选出活性成分,预测其相关靶点;通过UNIPROT数据库收集所有与嗅觉受体(olfactory receptor,OR)相关的蛋白;将筛选所得靶点和OR相关蛋白上传至STRING数据库进行蛋白相互作用分析;采用Cytoscape软件绘制靶点OR蛋白互作网络图,并进一步对关键靶点蛋白进行GO分析和KEGG通路富集分析。结果共获得陈皮有效成分5个、丁香有效成分5个、小茴香有效成分2个;药物靶点蛋白共224个;嗅觉受体相关基因515个。蛋白互作网络发现GNB2、CHRM2、CHRM3、GNGT2、ADRA2A等25个靶点是3味辛香类中药中挥发性成分激活OR后发挥药效的关键靶点。GO和KEGG富集分析确定了31个生物过程,78个信号通路。结论嗅觉受体主要被辛香类中药的挥发性成分激活,然后启动多个信号通路共同参与辛香类中药药性的表达,产生"气味辛香"之效。

Objective In this study, network pharmacology techniques and methods were used to screen the material basis, targets and pathways of the interaction between the pungent-aromatic herbs(Citri Reticulatae Pericarpium, Caryophylli Flos, and Foeniculi Fructus) and olfactory receptor. To explain the molecular mechanism of the expression of pungent properties of the pungent-aromatic herb. Methods TCMSP database was used to collect the chemical components of Citri Reticulatae Pericarpium, Caryophylli Flos, and Foeniculi Fructus, in order to screen out the effective components and predict the related targets. All the proteins related to olfactory receptors were collected from Uni Prot database. The selected targets and ORs proteins were uploaded to the online STRING database for protein interaction analysis. The interaction network was drawn by using the software of Cytoscape software, and the key targets was further analyzed by GO functional enrichment analysis and KEGG pathway enrichment analysis. Results Five active components of Citri Reticulatae Pericarpium, five of Caryophylli Flos and two of Foeniculi Fructus, 224 targets and 515 olfactory receptors were obtained. Protein interaction network showed 25 targets(such as GNB2, CHRM2, CHRM3, GNGT2, ADRA2A) were the key targets for ORs of three pungent-aromatic herbs. The enrichment analysis of GO and KEGG identified 31 biological processes and 78 signaling pathways. Conclusion Olfactory receptors are mainly activated by volatile oil components of the pungent-aromatic herb. And the classical cAMP signaling pathway may not be the only one after the olfactory receptor activated, which may be involved in the expression of pungent properties of the pungent-aromatic herb together with several other signaling pathways, so as to produce "pungent flavor".