基于网络药理学方法预测定喘汤治疗慢性阻塞性肺疾病的作用机制及验证研究

扫码查看

原文链接

万方数据
维普

中文摘要：目的:分析定喘汤治疗慢性阻塞性肺疾病(COPD)的分子机制,并通过细胞实验验证定喘汤的药理学作用.方法:在中药系统药理学数据库与分析平台(TCMSP)数据库中,对定喘汤9味中药进行有效成分筛选,利用UniPort数据库得到中药活性成分相关靶点.随后在五大疾病数据库中以COPD作为关键词进行检索,收集疾病对应的靶点基因.对有效成分-交集靶点网络进行拓扑分析,根据中药有效成分与交集靶点之间连接情况筛选定喘汤治疗COPD关键成分.最后通过基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析确定定喘汤治疗机制并进行分子对接,从整体生物网络角度阐述定喘汤治疗COPD的免疫炎症机制,并通过细胞实验加以验证.结果:本实验筛选得到定喘汤274个活性成分,与疾病交集靶点262个.KEGG富集分析表明核心靶点作用于白细胞介素-17(IL-17)信号通路、NOD样受体信号通路及趋化因子信号通路等多种免疫和炎症反应相关的信号通路,分子对接显示核心化合物与靶点具有良好的对接活性.细胞实验表明,定喘汤能通过磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)信号通路,抑制人Ⅱ型肺泡上皮细胞炎症反应,证实了网络药理学的作用靶点.结论:通过网络药理学的初步筛选与预测,已经初步明确定喘汤治疗COPD靶点,确定了定喘汤多通路作用机制,其有效成分可以通过PI3K/AKT信号通路调控炎症反应,从而达到治疗COPD的目的,可为后续的深入研究提供方向.

外文标题：Mechanism Prediction and Validation of Dingchuan Decoction in the Treatment of Chronic Obstructive Pulmonary Disease by Network Pharmacology

外文摘要：Objective:To analyze the molecular mechanism of Dingchuan Decoction in the treatment of chronic obstructive pulmo-nary disease(COPD)and verify the therapeutic effect of Dingchuan Decoction through cell experiments.Methods:In the TCMSP database,the active components of nine kinds of traditional Chinese medicine(TCM)in Dingchuan Decoction were screened,and the relevant targets of active components of TCM were obtained by the Uniport database.Then,the target genes corresponding to the diseases were collected by searching the keyword COPD in the five disease databases.Topological analysis was carried out on the network of active components-intersection targets,and the key components of Dingchuan Decoction in treating COPD were selected according to the connection between active components of TCM and intersection targets.Finally,the therapeutic mechanism of Ding-chuan Decoction was determined by gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis,and molecular docking was carried out.The immune and inflammatory mechanism of Dingchuan De-coction in treating COPD was clarified from the perspective of the whole biological network,and it was verified by cell experiment.Results:A total of 274 active components in Dingchuan Decoction and 262 disease-related intersection targets were screened through the experiment.KEGG enrichment analysis showed that the core target acted on the interleukin-17(IL-17)signaling path-way,NOD-like receptor signaling pathway,chemokine signaling pathway,and other immune and inflammatory signaling pathways.Molecular docking showed that the core compound had good docking activity with the target.Cell experiments showed that Ding-chuan Decoction could inhibit the inflammatory reaction of human type Ⅱ alveolar epithelial cells through the PI3K/AKT signaling pathway,which confirmed the action target of network pharmacology.Conclusion:Through the preliminary screening and prediction of network pharmacology,the target of Dingchuan Decoction in the treatment of COPD has been preliminarily defined,and the multi-channel action mechanism of Dingchuan decoction has been confirmed.Its active components can regulate the inflammatory re-sponse through the PI3K/AKT signaling pathway,so as to treat COPD,which points out a direction for subsequent in-depth re-search.

外文关键词：

Dingchuan DecoctionChronic obstructive pulmonary diseaseNetwork pharmacologyPI3K/AKTInflammatory re-actionMolecular dockingCell experimentTargets

作者：

徐国睿、冯湘仪、曲怡、王建波、刘海涛、马永钢、张立德

展开 >

作者单位：

辽宁中医药大学针灸推拿学院,沈阳,110847

中医脏象理论及应用教育部重点实验室,沈阳,110847

辽宁中医药大学,沈阳,110847

解放军总医院京西医疗区,北京,100144

展开 >

关键词：

定喘汤慢性阻塞性肺疾病网络药理学磷脂酰肌醇3激酶/蛋白激酶B 炎症反应分子对接细胞实验靶点

基金：

国家重点基础研究发展计划(973计划)国家自然科学基金青年科学基金辽宁省中央引导地方科技发展专项

项目编号：

2012CB518503813028802018416016

出版年：

2024

DOI：

10.3969/j.issn.1673-7202.2024.04.001

世界中医药

世界中医药学会联合会

世界中医药

CSTPCDCHSSCD北大核心

影响因子：1.266

ISSN：1673-7202

年,卷(期)：2024.19(4)

参考文献量26