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‐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. British Journal of Pharmacology (2008) 154 , 812–824; doi: 10.1038/bjp.2008.137 ; published online 21 April 2008