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


METHODS
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.


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
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.
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
M S
MS
Islam
T
T
Murata
M
M
Fujisawa
R
R
Nagasaka
H
H
Ushio
A M
AM
Bari
M
M
Hori
H
H
Ozaki
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003373:Coumaric Acids / Q000302:isolation & purification / Q000494:pharmacology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D012275:Oryza / Q000737:chemistry; D010666:Phenylpropionates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010840:Phytosterols / Q000302:isolation & purification / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003373:Coumaric Acids; D016328:NF-kappa B; D010666:Phenylpropionates; D010840:Phytosterols; D016264:Dextran Sulfate; C004999:ferulic acid; D024502:alpha-Tocopherol; C013172:gamma-oryzanol