[关键词]
[摘要]
目的 运用网络药理学及分子对接技术探究鼻渊通窍颗粒治疗慢性鼻窦炎的作用机制。方法 通过设置药物的参数范围在TCMSP平台筛选鼻渊通窍颗粒的活性成分,并挖掘各个活性成分相对应的靶点,在DrugBank、GeneCards、OMIM、PharmGKB和DisGeNET数据库探索“慢性鼻窦炎”的有关靶点,将上述共同靶点导入String数据库,获得蛋白相互作用(PPI)网络,利用Cytoscape 3.8.0的CytoNCA插件获取网络核心靶点。再利用R语言进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,采用Cytoscape 3.8.0软件进行“药物–活性成分–作用靶点–疾病”网络模型构建与分析,最后使用Sybyl软件进行核心靶点和药物成分的分子对接并预测其结合能力。结果 鼻渊通窍颗粒有14种药物组分,共筛选出149个活性成分,这些活性成分和慢性鼻窦炎的共同靶点有85个,其中核心靶点有7个,主要与血脂和动脉粥样硬化通路、人巨细胞病毒感染通路、PI3K/Akt信号通路、白细胞介素-17信号通路等相关。分子对接结果显示,核心靶点与活性成分均有一定的结合活性,其中CASP3与汉黄芩素、β-谷甾醇、千层纸素A、黄芩素、刺槐素,JUN与β-谷甾醇具有较好的结合活性。结论 鼻渊通窍颗粒可能从抑制炎症反应、参与免疫调节、防止氧化应激、调节脂质代谢以及提高黏液纤毛传输功能等多方面发挥对慢性鼻窦炎的治疗作用,为慢性鼻窦炎的治疗提供理论依据和新思路。
[Key word]
[Abstract]
Objective To explore the mechanism of Biyuan Tongqiao Granules in treatment of chronic sinusitis by using network pharmacology and molecular docking technology. Methods The active ingredients of Biyuan Tongqiao Granules were screened on TCMSP platform by setting the parameter range of drugs, and the corresponding targets of each active ingredient were explored. Explore "chronic sinusitis" targets at DrugBank, GeneCards, OMIM, PharmGKB, and DisGeNET databases. The above common targets were imported into the String database to obtain the protein interaction (PPI) network. The network core target was obtained by using Cytoscape 3.8.0 CytoNCA plug-in. R software was used for enrichment analysis of GO and KEGG pathways. Cytoscape 3.8.0 software was used to construct and analyze the network model of "drug-active component-target-disease". Finally, Sybyl software was used to conduct molecular docking between the core target and the drug component and predict its binding ability. Results Biyuan Tongqiao Granules contains 14 drug components, and a total of 149 active components were screened out. There are 85 common targets between these active components and chronic sinusitis, including 7 core targets, mainly including lipid and atherosclerosis pathway, human cytomegalovirus infection pathway, PI3K-Akt signaling pathway, interleukin-17 signaling pathway, etc. The results of molecular docking showed that the core targets showed certain binding activity with the active ingredients, among which CASP3 showed good binding activity with baicalein, β-sitosterol, melaletin A, baicalein, acacetin, JUN showed good binding activity with β -sitosterol. Conclusion Biyuan Tongqiao Granules may play a role in treatment of chronic sinusitis from the aspects of inhibiting inflammatory response, participating in immune regulation, preventing oxidative stress, regulating lipid metabolism and improving mucociliary transport function, providing a theoretical basis and new ideas for the treatment of chronic sinusitis.
[中图分类号]
R285
[基金项目]
湖南省卫生健康委科研计划项目(20200004);长沙市科技计划项目(kq1907010)