Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis

Sci Rep. 2016 Feb 25:6:22251. doi: 10.1038/srep22251.

Abstract

The natural polyphenol compound resveratrol (RSV) is considered to have a broad spectrum of beneficial biological activities upon human health. However, the exact effect of RSV on steatosis (a phenotype of non-alcoholic fatty liver [NAFL]) or fibrosis and inflammation (major phenotypes of non-alcoholic steatohepatitis [NASH]) is not known. Our data showed that administration of RSV (2 or 20 mg/kg/day) did not suppress steatosis in a high-fat diet-induced model of NAFL in mice. In contrast, identical concentrations of RSV dramatically inhibited inflammation and fibrosis in a low-dose lipopolysaccharide-induced model of NASH. These data suggested that RSV administration-mediated improvement of inflammation and fibrosis was due to the inhibition of LPS reactivity controlled by CD14 expression in Kupffer cells. These findings suggest that RSV could be a candidate agent for the treatment of NASH.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cell Line
  • Disease Models, Animal*
  • Fibrosis / genetics
  • Fibrosis / metabolism
  • Fibrosis / prevention & control
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Humans
  • Immunoblotting
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • STAT3 Transcription Factor
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Resveratrol