title: Carnosic acid alleviates chronic alcoholic liver injury by regulating the SIRT1/ChREBP and SIRT1/p66shc pathways in rats.
abstract: Carnosic acid (CA), which is extracted from rosemary, displays multiple pharmacological activities. This study aimed to investigate the effects of CA on chronic alcoholic liver injury and to elucidate the related mechanisms.
  
  
  
  An in vivo rat model was established by feeding rats a liquid diet containing ethanol, and an in vitro model was created by treating HepG2 cells with 100 mM ethanol for 48 h. In the rat model of alcohol-induced liver injury, CA significantly decreased serum aminotransferase, triglyceride and total cholesterol levels. Additionally, CA inhibited oxidative stress, inflammation, and cell death. Interestingly, CA activated SIRT1, which was associated with the downregulation of lipoprotein carbohydrate response element-binding protein (ChREBP) and growth factor adapter protein (p66shc). In HepG2 cells, ethanol-induced cell injury was associated with decreased SIRT1 and increased ChREBP and p66shc protein expression. These changes were reversed by CA but enhanced by a specific SIRT1 inhibitor, EX527. Moreover, the effects of CA on SIRT1, ChREBP, and p66shc were abolished by SIRT1 siRNA or EX527, indicating that CA decreased ChREBP and p66shc expression via SIRT1 activation.
  
  
  
  CA exerted protective effects against alcoholic liver injury by activating the SIRT1/ChREBP and SIRT1/p66shc pathways, which are related to the anti-steatosis, anti-oxidant, and anti-apoptosis effects.
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.|Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Shan
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, China. yaojihong65@hotmail.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1 / Q000378:metabolism
chemical_list: D045784:Abietanes; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C442825:Mlxipl protein, rat; D017382:Reactive Oxygen Species; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000431:Ethanol; C447939:SIRT1 protein, human; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C018381:salvin
keywords: Alcoholic liver injury; Carnosic acid; ChREBP; SIRT1; p66shc