基于网络药理学的福建野鸦椿果三萜抗肝纤维化的药效机制研究  

Network pharmacology of triterpenoids from the fruits of Euscaphis fukienensis Hsu.against liver fibrosis

作　　者：蒋佩佳 洪译 谭洋[1] 周峰 肖锦仁[1] 裴刚[1,2] JIANG Pei-jia;HONG Yi;TAN Yang;ZHOU Feng;XIAO Jin-ren;PEI Gang(School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208;Hunan Engineering Technology Center for Standardization and Function for Chinese Herbal Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学药学院,长沙410208 [2]湖南省中药饮片标准化与功能工程技术中心,长沙410208

出　　处：《中南药学》2021年第8期1524-1532,共9页Central South Pharmacy

基　　金：国家自然科学基金资助面上项目(No.81874424);湖南中医药科研计划重点项目(No.201805);湖南中医药大学中药一流学科资助。

摘　　要：目的研究福建野鸦椿果三萜类成分(EFT)抗肝纤维化的作用,并通过网络药理学探讨其治疗肝纤维化的作用机制。方法通过皮下注射四氯化碳建立肝纤维化小鼠模型,造模成功后给予EFT(5.12 mg·10 g^(-1))灌胃进行干预,以秋水仙碱(0.1 mg·kg^(-1))作为阳性对照。给药6周后采集小鼠血清和肝组织样本,观察肝组织病理变化,测量血清中的肝酶/功能指标,以及透明质酸和层粘连蛋白水平。参考文献筛选出EFT,运用SWISS数据库对EFT预测的作用靶点进行整合。通过HPO、DRUGBANK、OMIM数据库,筛选肝纤维化疾病作用靶点。在STRING数据库中导入以上数据,对EFT靶点与肝纤维化疾病相关靶点进行蛋白质相互作用分析,借助Cytoscape 3.7.2 软件构建EFT活性成分-作用靶点网络,并通过DAVID数据库对其结果进行信号通路和生物途径分析,得出EFT抗肝纤维化相应的作用机制。结果动物实验结果表明,EFT干预后可显著改善肝纤维化小鼠的肝组织结构,并恢复肝酶/功能指标水平,降低血清中透明质酸和层粘连蛋白的浓度。网络药理学分析得出福建野鸦椿果对肝纤维化的治疗作用可能是通过干预机体叉头转录因子信号通路,过氧化物酶体增殖物激活受体,Toll样受体信号通路,胰岛素抵抗、血管内皮生长因子信号通路、沙门氏菌感染相关信号通路来实现的。结论本研究表明三萜可能是福建野鸦椿果治疗肝纤维化的物质基础。网络药理学分析展现了EFT活性成分治疗肝纤维化的复杂网络,并为深入研究福建野鸦椿果提供科学依据。Objective To determine the anti-liver fibrosis effect of triterpenoids from the fruits of Euscaphis fukienensis Hsu.(EFT),and its mechanisms based on network pharmacology.Methods The liver fibrosis model was estalished by injecting carbon tetrachloride subcutaneously.EFT(5.12 mg·10 g^(-1))by gavage was performed,and colchicine(0.1 mg·kg^(-1))was used as the positive control.After the weeks treatment,the serum and liver tissue samples of mice were collected.Hepatic histology was observed,and hepatic enzymes/function indicators and the levels of hyaluronic acid and laminin in the serum were measured.SWISS database was used to integrate the predicted targets of the triterpenoid compositions from the fruits of Euscaphis fukienensis Hsu..HPO,DRUGBANK,and OMIM databases were collected to screen the targets of liver fibrosis.The above were was imput to STRING database to analyze the protein interactions.Cytoscapy 3.7.2 software was used to build the network of triterpenoid active ingredients-action targets.DAVID database was used to analyze the signal pathway and biological pathway of the potential mechanism of EFT treatment for liver fibrosis.Results EFT significantly improved the liver tissue structures in mice with liver fibrosis,restored the level of liver enzymes/function indicators,and reduced the concentration of fibrin in the serum.Network pharmacological analysis showed that the therapeutic effect of EFT on the liver fibrosis may be through the intervention of FoxO signaling pathway,PPAR signaling pathway,Toll-like receptor signaling pathway,insulin resistance,VEGF signaling pathway and Salmonella infection.Conclusion EFT can ameliorate carbon tetrachloride-induced liver fibrosis,indicating triterpenoids may be the material basis of the fruits of EFT for liver fibrosis.Network pharmacology exhibits a complex network of triterpenoid ingredients from EFT for liver fibrosis,and provides a scientific basis for further research.

关 键 词：福建野鸦椿果 三萜 肝纤维化 网络药理学 

分 类 号：R96[医药卫生—药理学]