世界中医药

作者	单位
郭朋程1,2，王婷3，童应鹏3，谢振达3，姜春筱3，周戚3，王建新1，2，3	1 复旦大学药学院药剂学系，智能化递药教育部重点实验室，上海，201203； 2 复旦大学中西医结合研究院药物研究所，上海，201203； 3 台州学院，高等研究院天然产物与健康产品研究所，台州，318000

摘要点击次数: 549

全文下载次数: 0

中文摘要:

目的：通过药效学评价、网络药理学和分子对接等研究方法探讨维药罗欧咳祖帕(LKZP)治疗哮喘的潜在功效成分和作用机制。方法：采用卵蛋白(OVA)诱导的哮喘模型小鼠研究LKZP抗哮喘的活性；整理出文献中LKZP的化学成分，预测其符合Lipinski规则化合物的作用靶点，并与哮喘疾病靶点进行交集分析，从而确定LKZP抗哮喘的治疗靶点。采用String数据库构建治疗靶点的蛋白质-蛋白质相互作用（PPI）网络，确定该网络中的核心靶点，并利用DAVID平台对核心靶点进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析，采用Cytoscape软件构建成分-靶点-信号通路的网络，采用分子对接的方法计算关键活性成分与靶点之间的结合能。结果：LKZP中共有潜在的活性化合物136个和841个作用靶点，而其核心靶点共66个。网络拓扑结构分析表明，LOKZP的核心治疗靶点为MAPK1、EGFR、MAPK3、PIK3CA、AKT1、PIK3CB、PIK3CD、PIK3R1和PRKCA等，而其作用的信号通路主要包含与调节气道炎症相关的PI3K-AKT信号通路、ErbB信号通路和雌激素信号通路，以及与调节气道重塑相关的HIF-1信号通路、VEGF信号通路和钙信号通路。分子对接的结果表明关键活性成分与靶点之间能较强结合。结论：LKZP中的关键活性成分倍半萜类、黄酮类和苯丙素类成分通过多靶点和多通路的方式调节气道炎症和气道重塑，从而发挥治疗哮喘的作用。

English Summary:

To explore the potential active components and mechanism of Loki zupa(LKZP) for asthma treatment through pharmacodynamic evaluation，network pharmacology and molecular docking.Methods:The anti-asthmatic activity of LKZP was studied in ovalbumin(OVA)-induced asthma model mice.The chemical components of LKZP collected from literature and their targets were screened by Lipinsk's Rule of Five.After their intersection with the asthma targets，the anti-asthma targets of LKZP were determined.The core targets of LKZP for asthma treatment were determined by constructing a protein-protein interaction(PPI) network of therapeutic targets using the String.Then GO and KEGG enrichment analyses were proformed on the core targets by the DAVID.Finally，a component-target-pathway network was built by Cytoscape，and the binding energy of active components and targets was calculated by molecular docking.Results:A total of 136 potential active compounds and 841 targets of LKZP were screened，with 66 core targets.According to the network analysis，the key targets of LKZP for asthma treatment were MAPK1，EGFR，MAPK3，PIK3CA，AKT1，PIK3CB，PIK3CD，PIK3R1 and PRKCA.The signaling pathways were mainly related with the regulation of airway inflammation(such as PI3K-Akt signaling pathway，ErbB signaling pathway，and estrogen signaling) and the regulation of airway remodeling(such as HIF-1 signaling pathway，VEGF signaling pathway，and calcium signaling pathway).Finally，the molecular docking indicated a strong binding energy between key active components and targets.Conclusion:Sesquiterpenes，flavonoids and phenylpropanoids，the key active components in LKZP，regulate the airway inflammation and airway remodeling by multiple targets and pathways，thereby treating asthma.

查看全文查看/发表评论下载PDF阅读器