title: Chlorogenic acid inhibits cholestatic liver injury induced by α-naphthylisothiocyanate: involvement of STAT3 and NFκB signalling regulation.
abstract: OBJECTIVE
  Chlorogenic acid (CGA) is one of the most widely consumed polyphenols in diets and is recognized to be a natural hepatoprotective agent. Here, we evaluated the protective effect and the potential mechanism of CGA against ɑ-naphthylisothiocyanate (ANIT)-induced cholestasis and liver injury.
  
  
  METHODS
  Twenty-five male 129/Sv mice were administered with CGA, and ANIT challenge was performed at 75 mg/kg on the 4th day. Blood was collected and subjected to biochemical analysis; the liver tissues were examined using histopathological analysis and signalling pathways.
  
  
  RESULTS
  Chlorogenic acid almost totally attenuated the ANIT-induced liver damage and cholestasis, compared with the ANIT group. Dose of 50 mg/kg of CGA significantly prevented ANIT-induced changes in serum levels of alanine aminotransferase, alkaline phosphatases, total bile acid, direct bilirubin, indirect bilirubin (5.3-, 6.3-, 18.8-, 158-, 41.4-fold, P<0.001) and aspartate aminotransferase (4.6-fold, P<0.01). Expressions of the altered bile acid metabolism and transport-related genes were normalized by cotreatment with CGA. The expressions of interleukin 6, tumour necrosis factor-α and suppressor of cytokine signalling 3 were found to be significantly decreased (1.2-fold, ns; 11.0-fold, P<0.01; 4.4-fold, P<0.05) in the CGA/ANIT group. Western blot revealed that CGA inhibited the activation and expression of signal transducer and activator of transcription 3 and NFκB.
  
  
  CONCLUSIONS
  These data suggest that CGA inhibits both ANIT-induced intrahepatic cholestasis and the liver injury. This protective effect involves down-regulation of STAT3 and NFκB signalling.
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province, Hunan Normal University, Changsha, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Ningbo College of Health Sciences, Ningbo, China.
authors.forename: Julin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province, Hunan Normal University, Changsha, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Caide
authors.initials: C
authors.lastname: Lu
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Danjun
authors.initials: D
authors.lastname: Song
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province, Hunan Normal University, Changsha, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Ye
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Manyun
authors.initials: M
authors.lastname: Dai
authors.affiliation: Laboratory of Metabolism, National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
authors.affiliation: Key Laboratory of Phytochemical R&D of Hunan Province, Hunan Normal University, Changsha, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
mesh_terms: D015058:1-Naphthylisothiocyanate; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000517:prevention & control; D002726:Chlorogenic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D002779:Cholestasis / Q000378:metabolism* / Q000517:prevention & control; D016207:Cytokines / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts; D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D059808:Polyphenols; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D002726:Chlorogenic Acid; D015058:1-Naphthylisothiocyanate; D001663:Bilirubin
keywords: NFκB; STAT3; chlorogenic acid; cholestasis; α-naphthylisothiocyanate