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

Abstract

BACKGROUND AND PURPOSE:

We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-kappaB (NF-kappaB) activity in macrophages. In the present study, we investigated the effect of gamma-oryzanol (gamma-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of gamma-ORZ, and ferulic acid (FA), a possible metabolite of gamma-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-kappaB 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-kappaB p65 nuclear translocation and inhibitory protein of nuclear factor-kappaB-alpha degradation levels were significantly increased in DSS-induced colitis tissues. gamma-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 gamma-ORZ and CAF had strong antioxidant effects comparable to those of alpha-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-kappaB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates.

• Authors: M S Islam, T Murata, M Fujisawa, R Nagasaka, H Ushio, A M Bari, M Hori, H Ozaki
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 154 Issue 4 Pg. 812-24 (Jun 2008) ISSN: 0007-1188 [Print] England
• PMID: 18536734 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Coumaric Acids
• NF-kappa B
• Phenylpropionates
• Phytosterols
• Dextran Sulfate
• ferulic acid
• alpha-Tocopherol
• gamma-oryzanol

Topics

• Animals
• Anti-Inflammatory Agents (isolation & purification, pharmacology)
• Antioxidants (isolation & purification, pharmacology)
• Colitis (chemically induced, drug therapy)
• Coumaric Acids (isolation & purification, pharmacology)
• Dextran Sulfate
• Disease Models, Animal
• Intestinal Mucosa (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (drug effects, metabolism)
• Oryza (chemistry)
• Phenylpropionates (chemistry, isolation & purification, pharmacology)
• Phytosterols (isolation & purification, pharmacology)
• alpha-Tocopherol (pharmacology)