基于GC-MS与生物信息学探讨矮地茶中挥发油治疗慢性阻塞性肺疾病的主要活性成分及作用机制

Exploring the Main Active Components and Mechanism of Volatile Oil in Ardisia Japonica for the Treatment of Chronic Obstructive Pulmonary Disease Based on GC-MS and Bioinformatics

关键词:  矮地茶  挥发油  气相色谱-质谱联用  网络药理学  分子对接

Key words:  Ardisia japonica  volatile oil  GC-MS  network pharmacology  molecular dockin

摘要:

目的 基于GC-MS技术和系统生物学方法预测矮地茶挥发性成分治疗慢性阻塞性肺疾病(chronicobstructive pulmonary disease,COPD)的作用机制。方法 采用GC-MS分析矮地茶挥发油成分并通过面积归一化法确定各成分的相对含量,利用TCMID、TCMSP、PharmMapper数据库筛选矮地茶挥发油主要活性成分与靶点,运用Cytoscape软件构建矮地茶“成分-靶点”网络,OMIM、Genecards数据库挖掘COPD相关靶点,利用String数据库和Cytoscape软件构建并绘制蛋白互作网络;通过Metascape数据库进行通路富集分析;进一步借助DiscoveryStudio(Version4.5)软件评估化合物与核心靶点的亲和能力。结果 筛选出5个主要共有活性成分,潜在靶点154个,核心靶点包括NTRK1、TNF、VEGFA、MAPK1和M2C2。通过GO富集分析得到2665个条目(P<0.05),其中包括生物过程2220条,分子功能233条,细胞组分212条。KEGG通路为242条(P<0.05),主要涉及血管内皮生长因子(vascular endothelial growth factor,VEGF)、肿瘤坏死因子(tumor necrosis factor,TNF)、NF-κB信号通路。分子对接结果显示石竹烯、蛇麻烯、依兰烯与核心靶点有较高的结合能力。结论 矮地茶挥发油可能通过TNF、VEGFA、MAPK1等靶点调节VEGF、TNF、NF-κB等通路治疗COPD。

Abstract:

OBJECTIVE To predict the mechanism of action of the volatile components of Ardisia japonica in the treatment of chronic obstructive pulmonary disease(COPD) based on GC-MS technology and systems biology.METHODS GC-MS method was used to analyze the volatile oil of Ardisia japonica and the relative content of each component was determined by the area normalization method. The main active components and targets of the volatile oil of Ardisia japonica were screened by TCMID, TCMSP, and PharmMapper database. The “component-target” network of Ardisia japonica was constructed by Cytoscape software. OMIM and Genecards database was used to mine COPD related targets, String database and Cytoscape software was used to construct and map protein-protein interaction network; conduct pathway enrichment analysis was established through Metascape database; further rely on Discovery Studio(Version 4.5) to evaluate the affinity of the compound with the core target of COPD.RESULTS A total of 5 main common active components and 154 potential targets were screened. The core targets included NTRK1, TNF, VEGFA, MAPK1 and M2C2. Through GO enrichment analysis, 2665 items(P<0.05) were obtained, including 2220 items for biological processes, 233 items for molecular functions, and 212 items for cell components. There were 242 KEGG pathways(P<0.05), mainly involving vascular endothelial growth factor(VEGF),tumor necrosis factor(TNF), and NF-κB signaling pathways. The results of molecular docking showed that caryophyllene,humulene, and ylangene had high binding ability to the core target.CONCLUSION Ardisia japonica volatile oil may regulate VEGF, TNF, NF-κB and other pathways to treat COPD through TNF, VEGFA, MAPK1 and other targets.