title: Hepatoprotective effect of fermented ginseng and its major constituent compound K in a rat model of paracetamol (acetaminophen)-induced liver injury.
abstract: OBJECTIVE
  This work aimed at evaluating the effect of fermented ginseng (FG) and fermented red ginseng (FRG) against rat liver injury caused by paracetamol (acetaminophen (APAP)).
  
  
  METHODS
  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum and histopathological changes in the liver were analysed to determine the degree of liver injury. Deoxyribonucleic acid (DNA) microarray analysis was performed to compare gene expression levels altered in the rat livers. Phosphorylated Jun-N-terminal kinase (JNK) in human hepatocellular carcinoma (HepG2) cells were detected using western blot analysis to investigate the anti-inflammatory activity of compound K.
  
  
  RESULTS
  Pretreatment with FG, containing compound K at high concentration, attenuated AST as well as ALT levels in rats, while no obvious effect was observed in the group that received FRG, whose content of compound K was lower than that of FG. In addition, the results of our histopathological analysis were consistent with changes in the serum biochemical analysis. DNA microarray analysis indicated that JNK- and glutathione S-transferase (GST)-related genes were involved in the hepatotoxicity. Notably, compound K, a major ginsenoside in FG, inhibited the phosphorylation of JNK in HepG2 cells.
  
  
  CONCLUSIONS
  FG was shown to possess hepatoprotective activity against paracetamol (APAP)-induced liver injury better than FRG. Compound K might play an important role for an anti-inflammatory activity of FG by inhibiting JNK signalling in the liver.
authors.affiliation: Research & Development Center, Nagase and CO., LTD, Kobe, Hyogo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Igami
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shimojo
authors.forename: Hisatomi
authors.initials: H
authors.lastname: Ito
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kashiwada
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005285:Fermentation; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D005894:Panax; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar
chemical_list: D000082:Acetaminophen; D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; D048031:JNK Mitogen-Activated Protein Kinases; D010936:Plant Extracts; C112772:ginsenoside compound K
keywords: DNA microarray; JNK phosphorylation; acetaminophen; compound K; fermented ginseng