基于网络药理学和分子对接技术研究鼻窦炎颗粒治疗慢性鼻窦炎的作用机制

Mechanism of Bidouyan Granules in treating chronic rhinosinusitis based on network pharmacology and molecular docking technology

摘要

目的 借助网络药理学和分子对接技术, 探讨鼻窦炎颗粒治疗慢性鼻窦炎 (CRS) 的药效成分及可能的作用靶点和机制。 方法 通过 TCMSP 数据库、HERB 数据库检索并筛选鼻窦炎颗粒活性成分及作用靶点, 利用 UniProt 数据库获取靶点基因; 利用 GeneCards 和 OMIM 数据库获取 CRS 的相关靶点; 通过 Venny 2.1.0 映射得到药物与疾病的交集靶点, 即潜在作用靶点; 在 Cytoscape 3.9.1 软件中分别导入中药、 活性成分与潜在靶点(交集靶点), 构建 “中药活性成分靶点” 图; 将药物与疾病的交集基因导入 STRING 平台和 Cytoscape 3.9.1 软件构建网络图; 通过 DAVID 数据库对交集靶点进行 GO 和 KEGG 富集分析; 最后采用分子对接软件对主要活性成分和核心靶点的结合作用力进行评价。 结果 筛选得到活性成分 215 个, 药物潜在作用靶点 1 087 个, CRS 相关作用靶点 1 159 个, 药物与疾病交集靶点 246 个; 主要活性成分包括槲皮素、 木犀草素等, 核心靶点有 TP53、STAT3、SRC、AKT1、PIK3R1、PIK3CA、HSP90AA1、IL6、PIK3CD、TNF 等; GO 富集分析结果包含对脂多糖应答、 对细菌分子反应、 膜区域、 膜筏、 跨膜受体蛋白酪氨酸激酶活性等; KEGG 富集结果包含 AGE-RAGE、PI3K-Akt、MAPK 信号通路等。 分子对接结果表明, 核心靶点与主要活性成分存在结合位点, 且结合能均小于 -12.552 kJ/mol, 结合较为稳定。 结论 鼻窦炎颗粒通过多成分、 多靶点、 多通路的作用机制, 通过促进机体抗炎、 抗凋亡、 增强免疫反应、 调控离子通道以及调节脂质代谢等生物学过程, 在治疗 CRS 中发挥作用。 本研究为鼻窦炎颗粒治疗 CRS 提供了科学依据, 并为进一步研究其药效作用机制奠定了基础。

Abstract

Objective To explore the pharmacodynamic components, potential action targets and mechanisms of Bidouyan Granules in the treatment of chronic rhinosinusitis (CRS) by means of network pharmacology and molecular docking technology. Methods The active ingredients and action targets of Bidouyan Granules were retrieved and screened through the TCMSP database and HERB database, and the target genes were obtained from UniProt database. The relevant targets of CRS were obtained using the GeneCards and OMIM databases. The intersection targets of the drug and the disease, that is, the potential action targets, were obtained through mapping with Venny 2.1.0. Traditional Chinese medicines, active ingredients and potential targets (intersection targets) were respectively imported into Cytoscape 3.9.1 software to construct a “traditional Chinese medicines active ingredients targets” diagram. The intersection genes of the drug and the disease were imported into the STRING platform and Cytoscape 3.9.1 software to construct a network diagram. GO and KEGG enrichment analyses were conducted on the intersection targets through the DAVID database. Finally, molecular docking software was used to evaluate the binding energy between the main active ingredients and the core targets. Results A total of 215 active components, 1 087 potential action targets of the drug, 1 159 action targets related to CRS, and 246 intersection targets of the drug and the disease were screened. The main active ingredients included quercetin, luteolin, etc. The core targets included TP53, STAT3, SRC, AKT1, PIK3R1, PIK3CA, HSP90AA1, IL6, PIK3CD, TNF, etc. The results of GO enrichment analysis included responses to lipopolysaccharide, responses to bacterial molecules, membrane regions, membrane rafts, transmembrane receptor protein tyrosine kinase activity, etc. The results of KEGG pathway enrichment analysis included the AGE-RAGE signaling pathway, the PI3K-Akt signaling pathway, the MAPK signaling pathway, etc. Molecular docking results showed that there were binding sites between the core targets and the main active ingredients, and the binding energies were less than -12.552 kJ/mol, indicating relatively stable binding. Conclusion Bidouyan Granules play a role in the treatment of CRS by promoting biological processes such as anti-inflammation, anti-apoptosis, enhancing immune response, regulating ion channels and regulating lipid metabolism in the body through multi-component, multi-target and multi-pathway mechanism. This study provides a scientific basis for the treatment of CRS with Bidouyan Granules, and lays a foundation for further research on its pharmacological mechanism.

关键词

网络药理学 / 分子对接 / 慢性鼻窦炎 / 中药复方 / PI3K-AKT 信号通路 / MAPK 信号通路 / 白细胞介素 6 / 肿瘤坏死因子 α

Key words

network pharmacology / molecular docking / chronic rhinosinusitis / Chinese herbal medicine compound / PI3K-Akt signaling pathway / MAPK signaling pathway / interleukin-6 / tumor necrosis factor-alpha

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基金资助

国家自然科学基金(81774190)

陕西省中医药管理局中医药传承创新暨 “秦药” 开发重点科学研究项目(21zyyqy)