基于网络药理学研究杜仲叶提取物改善非酒精性脂肪肝的作用及机制

  目的  基于网络药理学探讨杜仲叶提取物(Eucommia ulmoides leaf extracts, ELE)改善非酒精性脂肪肝(Nonalcoholic fatty liver disease, NAFLD)的有效成分、作用靶点及可能的作用机制。  方法  使用CNKI、万方、TCMSP、Pubmed等数据库、获取并筛选杜仲叶活性成分; 使用TCMSP数据库和SwissTargetPrediction数据库检索并预测ELE活性成分的靶点; 使用Genecard数据库和Drugbank数据库收集NAFLD疾病的靶点; 使用String 11.0构建蛋白互作(Protein-protein interaction)网络图, 分析蛋白靶点之间的关系; 使用Cytoscape 3.7.1软件构建化合物-疾病靶点-通路网络图, 分析三者之间相互作用的关系; 使用DAVID数据库, 对靶点进行GO分析和KEGG通路富集分析, 并对关键靶点进行实验验证。  结果  ELE改善NAFLD疾病靶点网络主要包含9个化合物和35个靶点, 与脂质代谢相关的靶点有PPARα和CPT-1A, 与NAFLD相关的通路主要有胰岛素抵抗、AMPK信号通路。体内、体外实验发现ELE能通过激活AMPKα及增强靶点PPARα和CPT-1A的表达, 增强脂质氧化, 改善NAFLD。  结论  ELE能增强脂质代谢, 改善NAFLD, 其机制主要与AMPK信号通路相关。 

Eucommia Folium Extracts Alleviate Nonalcoholic Fatty Liver Disease in vivo and in vitro Based on the Network Pharmacology Study

  OBJECTIVE  To explore the active ingredients, targets and possible mechanism of ELE alleviating NAFLD based on the method of network pharmacology.  METHODS  The components in ELE were found in CNKI, Wanfang, TCMSP and Pubmed database. The components targets were found in TCMSP and swisstarget prediction database. NAFLD targets were found in genecard database and drugbank database. PPI network was established to analyze the interaction among targets by String 11.0 database. Compounds-targets-pathways network was established by the software of Cytoscape. Go and KEGG analysis were carried by david database. In addition the key targets were verified by cell and animals experiments.  RESULTS  The network of ELE against NAFLD contains 9 compounds and 35 targets. The targets related to lipid metabolism are PPARα and CPT-1A, and the signaling pathways mainly related to lipid metabolism are insulin resistance and AMPK signaling pathway. In vivo and in vitro experiments indicated that ELE could enhance lipid oxidation and improve NAFLD by activating AMPKα and enhancing the expression of PPARα and CPT-1A.  CONCLUSION  ELE can enhance lipid metabolism and improve NAFLD mainly related to AMPK signaling pathway.