Protective effect of fucoidan from Fucus vesiculosus on liver fibrosis via the TGF-β1/Smad pathway-mediated inhibition of extracellular matrix and autophagy

Drug Des Devel Ther. 2016 Feb 12:10:619-30. doi: 10.2147/DDDT.S98740. eCollection 2016.

Abstract

Liver fibrosis is a dynamic reversible pathological process in the development of chronic liver disease to cirrhosis. However, the current treatments are not administered for a long term due to their various side effects. Autophagy is initiated to decompose damaged or excess organelles, which had been found to alter the progression of liver fibrosis. In this article, we hypothesized that fucoidan from Fucus vesiculosus may attenuate liver fibrosis in mice by inhibition of the extracellular matrix and autophagy in carbon tetrachloride- and bile duct ligation-induced animal models of liver fibrosis. The results were determined using enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining. Fucoidan from F. vesiculosus could inhibit the activation of hepatic stellate cells and the formation of extracellular matrix and autophagosomes, and its effect may be associated with the downregulation of transforming growth factor beta 1/Smads pathways. Fucoidan, as an autophagy and transforming growth factor beta 1 inhibitor, could be a promising potential therapeutic agent for liver fibrosis.

Keywords: bile duct ligation; hepatic stellate cells; liver cirrhosis.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Beclin-1
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / physiology
  • Fucus / chemistry*
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / physiopathology
  • Male
  • Mice
  • Microtubule-Associated Proteins / antagonists & inhibitors
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Signal Transduction / physiology*
  • Smad Proteins / physiology*
  • Transforming Growth Factor beta1 / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, mouse
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Polysaccharides
  • Smad Proteins
  • Transforming Growth Factor beta1
  • fucoidan