Suppression by fucoidan of liver fibrogenesis via the TGF-β/Smad pathway in protecting against oxidative stress

Biosci Biotechnol Biochem. 2011;75(5):833-40. doi: 10.1271/bbb.100599. Epub 2011 May 20.

Abstract

Fucoidan, a sulfated polysaccharide extracted from various types of brown seaweed, possesses a wide range of pharmacological properties. We investigated the protective effect of fucoidan on dimethylnitrosamine-induced liver fibrogenesis in rats and its mechanism. Liver fibrosis was induced by injecting DMN (10 mg/kg, 3 times per week, I.P.) for 4 weeks, and fucoidan was simultaneously administered (100 mg/kg, 3 times per week, P.O.). The anti-oxidative and anti-inflammatory effects of fucoidan were observed by relative mediators. Fucoidan improved liver fibrosis by inhibiting the expression of transforming growth factor beta 1 (TGF-β(1))/Smad3 and the tissue inhibitor of metalloproteinase 1 (TIMP-1), and increasing the expression of metalloproteinase-9 (MMP-9). Fucoidan also significantly decreased the accumulation of the extracellular matrix (ECM) and collagen. These results suggest that fucoidan had an anti-fibrotic effect, which was exerted by inhibiting the TGF-β/Smad pathway, as well as anti-oxidative and anti-inflammatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Body Weight / drug effects
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / blood
  • Glutathione Peroxidase / metabolism
  • Inflammation Mediators / metabolism
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Male
  • Malondialdehyde / blood
  • Malondialdehyde / metabolism
  • Organ Size / drug effects
  • Oxidative Stress / drug effects*
  • Polysaccharides / pharmacology*
  • Polysaccharides / therapeutic use
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Smad Proteins / metabolism*
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • Antioxidants
  • Inflammation Mediators
  • Polysaccharides
  • RNA, Messenger
  • Smad Proteins
  • Transforming Growth Factor beta
  • Malondialdehyde
  • fucoidan
  • Glutathione Peroxidase
  • Superoxide Dismutase