Oral intake of chicoric acid reduces acute alcohol-induced hepatic steatosis in mice

Nutrition. 2014 Jul-Aug;30(7-8):882-9. doi: 10.1016/j.nut.2013.11.015. Epub 2013 Dec 5.

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.

Conclusion: 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.

Keywords: Alcohol; Chicoric acid; Endotoxin; Steatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Caffeic Acids / pharmacology
  • Caffeic Acids / therapeutic use*
  • Cichorium intybus / chemistry
  • Echinacea / chemistry
  • Ethanol
  • Fatty Liver, Alcoholic / drug therapy*
  • Fatty Liver, Alcoholic / metabolism
  • Female
  • In Vitro Techniques
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Lipopolysaccharides
  • Liver / drug effects*
  • Liver / metabolism
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plasminogen Activator Inhibitor 1 / metabolism
  • RNA, Messenger / metabolism
  • Succinates / pharmacology
  • Succinates / therapeutic use*
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Caffeic Acids
  • Lipopolysaccharides
  • Plant Extracts
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Succinates
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Nitric Oxide Synthase Type II
  • chicoric acid