基于网络药理学及动物实验探讨蒙药胡日查-6治疗变应性鼻炎的作用机制研究

Elucidation of the Mongolian medicine Huricha-6 mechanism in treating allergic rhinitis via network pharmacology and animal experiments

目的基于网络药理学及动物实验探讨蒙药胡日查-6治疗变应性鼻炎(allergic rhinitis,AR)的作用机制。方法从TCMSP数据库和文献获得胡日查-6的化合物及靶点,OMIM、TTD、Disgenet和GeneCards数据库搜索AR相关靶点,后将胡日查-6靶点与AR靶点取交集,构建“化合物—交集靶点”网络,选择关键化合物并应用STRING数据库绘制PPI蛋白互做网络进行核心靶点的筛选。使用R语言对交集靶点进行基因本体富集(gene ontology,GO)和京都基因与基因组百科全书(kyto encyclopedia of genes and genomes,KEGG)通路分析,借助AutoDockVina软件对关键化合物及靶点进行分子对接验证。构建AR豚鼠模型,以胡日查-6治疗6周后,对豚鼠鼻部症状进行行为学评分,取鼻黏膜组织进行HE染色观察病理改变,ELISA检测豚鼠血清IL-4、IFN-γ水平。结果筛选出胡日查-6治疗AR的可能靶点为107个,胡日查-6治疗AR相关的化合物30个,槲皮素、木犀草素、山柰酚、异鼠李素、奎宁等为关键化合物,核心靶点为VEGFA、STAT3、IL-1B、IL-6、ALB等。KEGG通路分析主要涉及TNF、IL-17、Toll样受体和HIF-1等多条信号通路,分子对接显示关键化合物与核心靶点之间具有较强的结合能力。动物实验表明,胡日查-6能够有效减轻豚鼠鼻部症状,改善鼻黏膜病理改变,降低豚鼠血清中IL-4水平,提高IFN-γ水平。结论胡日查-6通过多靶点、多通路治疗AR,并可能通过参与炎症反应减轻鼻黏膜组织炎性浸润、缓解AR。

Objective To explore the possible mechanism of Mongolian medicine Huricha-6 in treating allergic rhinitis,based on network pharmacology and animal experiments.Methods Compounds and targets of Huricha-6 were obtained from the TCMSP database and literature.Allergic rhinitis(AR)-related targets were identified via searches of the OMIM,TTD,Disgenet,and Gene-Cards databases.Then,the Huricha-6 target and AR target intersection was identified by constructing a"compound-intersection target"network and selecting key compounds.The STRING database was used to draw the protein interaction network to screen core targets,and R language was used to conduct gene ontology(GO)and kyto encyclopedia of genes and genomes(KEGG)pathway analysis on intersection targets.AutoDockVina software was used to verify key compounds and targets by molecular docking.An AR guinea pig model was constructed for Huricha-6 testing.Guinea pigs were treated with Huricha-6 for 6 weeks,then their nasal symptoms were evaluated by behavioral assessment.Nasal mucosa tissue was taken for HE staining to observe lesions,and IL-4 and IFN-γlevels were detected by ELISA.Results Network pharmacology analysis identified 107 possible targets for Huricha-6 relevant to AR treatment,and 30 compounds related to Huricha-6 in the treatment of AR.Quercetin,luteolin,kaolin,isorhamnetin and quinine were the key compounds,and the key target include VEGFA,STAT3,IL-1B,IL-6 and ALB.KEGG pathway enrichment revealed involvement of TNF,IL-17,Toll and HIF-1 pathways.Molecular docking supports the premise that key compounds will exhibit strong binding to core targets.Animal experiments demonstrate that Huricha-6 can effectively reduce nasal symptoms,improve pathological changes in the nasal mucosa,significantly reduce serum IL-4 levels,and increase IFN-γlevels.Conclusion Huricha-6 can ameliorate AR symptoms via interactions with multiple targets that act in multiple pathways,may alleviate inflammatory cell infiltration of nasal mucosal tissue,and alleviate AR symptoms by modulating the inflammatory response.