title: Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element binding protein 1 activity by way of the calcium/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mechanistic target of rapamycin-p70 ribosomal S6 kinase signaling pathway.
abstract: OBJECTIVE
  To investigate the effects of emodin on the treatment of non-alcoholic fatty liver and the underlying mechanisms.
  
  
  METHODS
  In vitro, hepatocytes were treated with 1 mM free fatty acid together with various concentrations of emodin. In vivo, Sprague-Dawley rats were divided into a control group, high-fat diet (HFD) group, and three HFD groups treated with 40, 80, and 160 mg/kg emodin, respectively. After being fed a HFD for 4 weeks, rats were orally dosed with emodin once daily for 8 weeks. The biochemical parameters and histology features were examined. The expression of lipogenic and lipolytic gene and protein and the phosphorylation of calcium/calmodulin-dependent kinase kinase (CaMKK), AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) and p70 ribosomal S6 kinase (p70S6K) were measured in vitro and in vivo.
  
  
  RESULTS
  Emodin improved lipid accumulation in vitro and in vivo. Emodin downregulated the levels of sterol regulatory element binding protein 1 (SREBP1) and its target enzymes but increased lipolysis-related proteins and mRNA. Phosphorylation of AMPK was increased, while phosphorylation of mTOR and p70S6K were suppressed by emodin. The nuclear translocation of SREBP1 was inhibited by emodin by AMPK and mTOR. Emodin activated AMPK by CaMKK and reversed the reduction of CaMKK in HFD-fed rats.
  
  
  CONCLUSIONS
  Emodin effectively ameliorates hepatic steatosis through the CaMKK-AMPK-mTOR-p70S6K-SREBP1 signaling pathway.
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
authors: Shaojie
authors: S
authors: Wang
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
authors: Xiaojie
authors: X
authors: Li
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
authors: Hongli
authors: H
authors: Guo
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
authors: Zihang
authors: Z
authors: Yuan
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.|Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, China.
authors: Tao
authors: T
authors: Wang
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.|Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, China Pharmaceutical University, Nanjing, China.
authors: Luyong
authors: L
authors: Zhang
authors: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.|Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China.
authors: Zhenzhou
authors: Z
authors: Jiang
keywords: AMP-activated protein kinase; emodin; mechanistic target of rapamycin; non-alcoholic fatty liver disease; sterol regulatory element binding protein 1