title: Oral intake of chicoric acid reduces acute alcohol-induced hepatic steatosis in mice.
abstract: OBJECTIVE
  Acute and chronic consumption of alcohol can alter intestinal barrier function thereby increasing portal endotoxin levels subsequently leading to an activation of toll-like receptor (TLR) 4-dependent signaling cascades, elevated levels of reactive oxygen species and induction of tumor necrosis factor α in the liver. Recent studies suggest that chicoric acid found in Echinacea pupurea, chicory, and other plants, may possess antioxidant and anti-inflammatory effects. The aim of the present study was to determine if chicoric acid can reduce acute alcohol-induced liver damage.
  
  
  METHODS
  Female mice were given chicoric acid orally (4 mg/kg body weight) for 4 d before acute ethanol administration (6 g/kg body weight). Furthermore, the effect of chicoric acid on the lipopolysaccharide (LPS)-dependent activation in an in vitro model of Kupffer cells (RAW264.7 macrophages) was assessed.
  
  
  RESULTS
  Acute alcohol ingestion caused a significant increase in hepatic triacylglycerols accumulation, which was associated with increased protein levels of the inducible nitric oxide synthase (iNOS), 4-hydroxynonenal protein adducts, and active plasminogen activator inhibitor 1 protein in the liver. Pretreatment of animals with chicoric acid significantly attenuated these effects of alcohol on the liver. In LPS-treated RAW264.7 macrophages, pretreatment with chicoric acid significantly suppressed LPS-induced mRNA expression of iNOS and tumor necrosis factor α.
  
  
  CONCLUSIONS
  These data suggest that chicoric acid may reduce acute alcohol-induced steatosis in mice through interfering with the induction of iNOS and iNOS-dependent signaling cascades in the liver.
authors.affiliation: SD Model Systems of Molecular Nutrition, Friedrich-Schiller University, Jena, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Landmann
authors.affiliation: SD Model Systems of Molecular Nutrition, Friedrich-Schiller University, Jena, Germany.
authors.forename: Giridhar
authors.initials: G
authors.lastname: Kanuri
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Spruss
authors.affiliation: Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Stahl
authors.affiliation: SD Model Systems of Molecular Nutrition, Friedrich-Schiller University, Jena, Germany. Electronic address: Ina.bergheim@uni-jena.de.
authors.forename: Ina
authors.initials: I
authors.lastname: Bergheim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002109:Caffeic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D018651:Cichorium intybus / Q000737:chemistry; D020900:Echinacea / Q000737:chemistry; D000431:Ethanol; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002109:Caffeic Acids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013386:Succinates; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II; C100435:chicoric acid
keywords: Alcohol; Chicoric acid; Endotoxin; Steatosis