title: Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice.
abstract: OBJECTIVE
  To investigate the potential protective effects of chlorogenic acid (CGA) on acute liver injury caused by lipopolysaccharide (LPS) in mice.
  
  
  METHODS
  C57BL/6J mice were pretreated with CGA (50 mg/kg, intraperitoneally) once per day for 5 days before an overnight LPS challenge (30 mg/kg, intraperitoneally). Severity of liver injury was assessed by histological analysis and determination of serum ALT and AST levels. Expression and activation of key regulators involved in the inflammatory response were determined, respectively, by real-time RT-PCR and western blotting.
  
  
  RESULTS
  In contrast to the yellow color of the liver in LPS-treated mice, CGA maintained the normal reddish appearance of the liver. Histological analysis indicated that CGA attenuated the infiltration of neutrophil cells and the necrosis of hepatocytes. CGA also decreased the elevated plasma levels of ALT and AST. At the transcriptional level, CGA pretreatment suppressed hepatic mRNA expression of toll-like receptor 4 (TLR4), TNF-alpha and NF-kappaB p65 subunit. In contrast, mRNA level of the transcriptional coactivator PGC-1alpha was restored by CGA. Finally, CGA reduced the phosphorylation of NF-kappaB p65 subunit in the liver.
  
  
  CONCLUSIONS
  Our data suggest that CGA has remarkable hepatoprotective effects on LPS-induced liver injury and that the possible mechanism is related to its anti-inflammatory action.
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210046, China.
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Xu
authors.forename: Jingwen
authors.initials: J
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.forename: Fengrong
authors.initials: F
authors.lastname: Jiang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D002726:Chlorogenic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D002726:Chlorogenic Acid
references.citation: Annu Rev Immunol. 1994;12:141-79
references.pmid: 8011280
references.citation: Infect Immun. 2002 Jul;70(7):3433-42
references.pmid: 12065483
references.citation: Int Immunopharmacol. 2009 Aug;9(9):1042-8
references.pmid: 19393773
references.citation: Biochem Pharmacol. 1989 Feb 15;38(4):627-31
references.pmid: 2465008
references.citation: J Nutr Biochem. 2002 Dec;13(12):717-726
references.pmid: 12550056
references.citation: J Biol Chem. 2001 Jun 15;276(24):21129-35
references.pmid: 11274165
references.citation: Biochim Biophys Acta. 1997 Jun 6;1335(3):335-42
references.pmid: 9202196
references.citation: Mol Cell Biol. 1996 Apr;16(4):1295-304
references.pmid: 8657102
references.citation: Genes Dev. 1995 Nov 15;9(22):2723-35
references.pmid: 7590248
references.citation: Food Chem Toxicol. 2000 May;38(5):467-71
references.pmid: 10762733
references.citation: Hepatology. 1990 Nov;12(5):1187-91
references.pmid: 2227817
references.citation: Cell Metab. 2005 Jun;1(6):361-70
references.pmid: 16054085
references.citation: Hepatology. 2006 Feb;43(2 Suppl 1):S99-S112
references.pmid: 16447287
references.citation: N Engl J Med. 2003 Jan 9;348(2):138-50
references.pmid: 12519925
references.citation: Oncogene. 1999 Nov 22;18(49):6853-66
references.pmid: 10602461
references.citation: Infect Immun. 2002 Jan;70(1):192-8
references.pmid: 11748182
references.citation: J Endotoxin Res. 2000;6(6):453-7
references.pmid: 11521070
references.citation: Am J Physiol Gastrointest Liver Physiol. 2009 Jan;296(1):G45-54
references.pmid: 18948440
references.citation: Hepatology. 2001 Jun;33(6):1441-50
references.pmid: 11391533
references.citation: Nucleic Acids Res. 2006 Feb 25;34(4):1216-23
references.pmid: 16500892
references.citation: Nature. 2002 Dec 19-26;420(6917):885-91
references.pmid: 12490963
references.citation: J Cell Mol Med. 2009 Sep;13(9B):3370-9
references.pmid: 19243473
references.citation: Cell. 2002 Apr;109 Suppl:S81-96
references.pmid: 11983155
references.citation: Toxicol Sci. 2002 Feb;65(2):166-76
references.pmid: 11812920
references.citation: Biol Pharm Bull. 2006 Nov;29(11):2236-40
references.pmid: 17077520
references.citation: Infect Immun. 1996 Mar;64(3):734-8
references.pmid: 8641774
references.citation: J Biol Chem. 2005 Jul 29;280(30):27888-95
references.pmid: 15944151
references.citation: Immunopharmacol Immunotoxicol. 2002 Feb;24(1):113-9
references.pmid: 12022439
references.citation: Shock. 2000 Feb;13(2):110-6
references.pmid: 10670840
references.citation: Immunity. 1999 Oct;11(4):443-51
references.pmid: 10549626
references.citation: Biochemistry (Mosc). 2004 Jan;69(1):70-4
references.pmid: 14972021
references.citation: Curr Opin Immunol. 1999 Feb;11(1):19-22
references.pmid: 10047547
references.citation: Biochem Pharmacol. 2002 Sep;64(5-6):963-70
references.pmid: 12213593