Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines  

作　　者：Lijuan Xue Keanqi Liu Caixia Yan Junling Dun Yexin Xu Linlin Wu Huizhu Yang Huafang Liu Lin Xie Guangji Wang Yan Liang 

机构地区：[1]Key Lab of Drug Metabolism&Pharmacokinetics,State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China [2]Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research,Department of Clinical Pharmacy,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China [3]Analytical Applications Center,Shimadzu(China)Co.,Ltd.,Shanghai 200233,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第8期3545-3560,共16页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Number:82274194);Jiangsu Natural Science Funds(Grant Number:BK20211224,China);the Project of State Key Laboratory of Natural Medicines(Grant Number:SKLNMZZ202001,China)。

摘　　要：Nonalcoholic steatohepatitis(NASH)is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder.Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH,while the other lipids associated with the NASH pathogenesis remained unexplored.The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids.Herein,multi-omics techniques based on LC—Q-TOF/MS,LC—MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment.A methionine and choline deficient(MCD)diet-induced mouse model of NASH was then constructed,and Schisandra lignans extract(SLE)was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14.Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines(PEs),and SLE could significantly reduce the accumulation of intrahepatic PEs.Notably,exogenous PE(18:0/18:1)was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis.Supplementing PE(18:0/18:1)also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors,while PE synthase inhibitor exerted a prominent hepatoprotective role.The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

关 键 词：Nonalcoholic steatohepatitis Multi-omics Schisandra lignans extract Phosphatidyle thanolamine PE(18:0/18:1) 

分 类 号：R57[医药卫生—消化系统]