Polydatin protects against carbon tetrachloride-induced liver fibrosis in mice

Arch Biochem Biophys. 2017 Sep 1:629:1-7. doi: 10.1016/j.abb.2017.06.017. Epub 2017 Jun 27.

Abstract

Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol, has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl4) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl4, the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl4-induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl4. Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.

Keywords: Inflammation; Liver fibrosis; Oxidative stress; Polydatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Animals
  • Carbon Tetrachloride / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Glucosides / pharmacology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics
  • Oxidative Stress / drug effects
  • Stilbenes / pharmacology*

Substances

  • Aldehydes
  • Glucosides
  • Stilbenes
  • Carbon Tetrachloride
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, mouse
  • 4-hydroxy-2-nonenal
  • polydatin