小青龙汤治疗变应性鼻炎作用机制的网络药理学分析

Mechanism of Xiaoqinglong Decoction in The Treatment of Allergic Rhinitis Based on Network Pharmacology and Molecular Docking

目的探索小青龙汤治疗变应性鼻炎(AR)的网络调控机制。方法通过TCMSP数据库筛选小青龙汤的活性成分;利用TCMSP数据库及UniProt数据库获取全部药物靶点;通过Genecards、OMIM、TTD及Drugbank数据库获取AR疾病靶点,与药物靶点取交集后得到小青龙汤对AR的潜在治疗靶点。通过Cytoscape 3.7.2软件构建小青龙汤治疗AR的“中药-活性成分-靶点”网络。通过STRING数据库构建潜在治疗靶点的蛋白相互作用(PPI)网络,采用Cytoscape 3.7.2软件进行可视化处理,同时以MCC拓扑法构建关键子网络并进行Cluster模块解析。借助CTD数据库对潜在治疗靶点进行GO和KEGG通路富集分析。运用分子对接技术验证小青龙汤活性成分与关键靶点的结合效能。结果小青龙汤的152个化合物可作用于116个AR疾病靶点。MCC分析得到PPI关键靶蛋白为白细胞介素(IL)6、肿瘤坏死因子(TNF)、CXCL8、IL-1B、PTGS2、IL-10等,均与炎性反应密切相关;Cluster模块分析提示关键靶点与炎症、血管收缩与循环系统、细胞因子刺激等相关。参与GO的生物过程、细胞组分、分子功能分别为31条、9条及2条;干预46条KEGG信号通路,如免疫系统、IL-4和IL-13信号通路、TNF信号通路。分子对接提示槲皮素、山柰酚及木犀草素与TNF的亲和力高于第二代H1受体拮抗剂依巴斯汀及氯雷他定。结论小青龙汤在治疗AR方面具有多成分、多靶点、多途径的整体调控特点,可能与通过槲皮素、山柰酚及木犀草素等活性成分作用于炎性因子,参与调节免疫系统及循环系统等有关。

Objective To investigate the mechanism of Xiaoqinglong decoction(XQLT)on allergic rhinitis(AR)through network pharmacology.Methods The active ingredients of Xiaoqinglong decoction were selected as the research objects,and all drug targets were obtained by TCMSP database and UniProt database.Disease targets of AR were obtained through Genecards,OMIM,TTD and Drugbank,and the potential therapeutic targets of XQLT were obtained after the intersection.Cytoscape 3.7.1 software was used to construct a visual network topological relationship map of the Active Ingredients-Targets.STRING database was used for constructing the PPI network,which was visually processed by Cytoscape 3.7.2,and simultaneously performed MCC topology analysis on key subnetworks and Cluster module analysis.The CTD database was used to carry out GO and KEGG enrichment for potential therapeutic targets.The molecular docking technology was used to verify the binding efficiency of the active ingredients of XQLT and key targets.Results The 152 compounds of XQLT can act on 116 disease targets of AR.MCC analysis showed that the key target proteins of PPI are IL-6,TNF,CXCL8,IL-1B,PTGS2,IL-10,etc.,which are closely related to inflammation.Cluster analysis suggests that the key target proteins are related to inflammation,vasoconstriction and circulatory system,and cytokine stimulation.The Biological Process,Cellular Components,and Molecular Function involved in GO are 31,9,and 2,respectively.46 KEGG signaling pathways were intervened,such as the immune system,IL-4 and IL-13 signaling pathways,and TNF signaling pathway.Molecular docking suggested that the affinity of quercetin,kaempferol and luteolin with TNF is higher than those of the second-generation H1 receptor antagonists,such as ebastine and loratadine.Conclusion XQLT has the multicomponent-multi-target-multi-channel overall regulation characteristics in the treatment of AR,acts on inflammatory factors,regulates the immune system and circulatory system,etc.,by quercetin,kaempferol and luteolin and other active ingredients.