論文

2008年6月21日

Anti-inflammatory effects of phytosteryl ferulates in colitis induced by dextran sulphate sodium in mice

British Journal of Pharmacology
  • M. S. Islam
  • ,
  • T. Murata
  • ,
  • M. Fujisawa
  • ,
  • R. Nagasaka
  • ,
  • H. Ushio
  • ,
  • A. M. Bari
  • ,
  • M. Hori
  • ,
  • H. Ozaki
  • ,
  • H. Ozaki

154
開始ページ
812
終了ページ
824
DOI
10.1038/bjp.2008.137

Background and purpose: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-κB (NF-κB) activity in macrophages. In the present study, we investigated the effect of γ-oryzanol (γ-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of γ-ORZ, and ferulic acid (FA), a possible metabolite of γ-ORZ in vivo, on a model of colitis in mice. Experimental approach: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-κB activity in colitis tissue. Key results: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-κB p65 nuclear translocation and inhibitory protein of nuclear factor-κB-α degradation levels were significantly increased in DSS-induced colitis tissues. γ-ORZ (50 mg kg -1 day -1 p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that γ-ORZ and CAF had strong antioxidant effects comparable to those of α-tocopherol. Conclusions and implications: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-κB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates. © 2008 Nature Publishing Group All rights reserved.

リンク情報
DOI
https://doi.org/10.1038/bjp.2008.137
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/18536734
Scopus
https://www.scopus.com/record/display.uri?eid=2-s2.0-44949119375&origin=inward
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=44949119375&origin=inward