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

Background and purpose: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-kappa B (NF-kappa B) 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 g-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-kappa B 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-kappa B p65 nuclear translocation and inhibitory protein of nuclear factor-kappa B-alpha degradation levels were significantly increased in DSS-induced colitis tissues. gamma-ORZ (50mgkg(-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-kappa B activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates.