Comparison of three tocopherol analogs as an inhibitor of production of proinflammatory mediators in macrophages

Anti-inflammatory effects of tocopherol (tol) analogs have been attributed to their potent antioxidant activities. however,we and others have separately reported that γtol or α-tocopheryl succinate (αtos),despite their lower antioxidant activities,inhibit lipopolysaccharide (lps)-induced production of prostaglandin e 2 (pge 2) in macrophages and lung epithelial cells more effectively than αtol. in the present study,we sought to directly analyze the effect of three tol analogs (αtol,αtos,and γtol) on lps-induced production of pro-inflammatory mediators in macrophages. our data demonstrated that the inhibitory effects of all three tol analogs on nitric oxide production were very limited. in contrast,αtos dose-dependently and significantly inhibited lps-induced pge 2 production in both raw264.7 cells and peritoneal macrophages,whereas αtol and γtol were much less effective. although αtos had no effect on lps-induced cyclooxygenase-2 expression,it did inhibit cox activity in intact cells. αtos in combination with sulforaphane,a compound that blocked lps-induced cox-2 expression,cooperatively and more significantly inhibited pge 2 production. these findings suggest that αtos is a more potent inhibitor of the pro-inflammatory mediator pge 2. the inclusion of αtos in vitamin supplements may further enhance the effectiveness of strategies for preventing diseases associated with inflammation. © the japanese pharmacological society.