Despite defenses by polymorphonuclear neutrophils in the host against invading agents, overproduction of oxidant species by phagocytes can lead to damage in the surrounding tissues. Several benzophenones have been shown to possess anti-inflammatory properties. The effect of the natural benzophenone 7-epiclusianone isolated from leaves of Garcinia brasiliensis was investigated by using in vitro antioxidant and ex vivo anti-inflammatory assays, focusing on the neutrophil respiratory burst and on the biochemical pathways involved. The bioactive extract, 7-epiclusianone, showed low in vitro antioxidant activity as evaluated by the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, the reducing power test, or the chelating power assay. However, the benzophenone displayed potent activity in the ex vivo model of the neutrophil respiratory burst, inhibiting the generation of superoxide anions in a dose-dependent manner. When the respiratory burst was triggered by N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, the 50% effective concentration (EC(50)) was 41.18 μg/10(7) cells. When phagocytes were stimulated directly through protein kinase C via phorbol, the EC(50) was 34.3 μg/10(6) cells. The results indicated that 7-epiclusianone was able to down-regulate inflammatory phagocyte superoxide anion release through a mechanism controlled by tyrosine protein phosphorylation and by a direct stimulation of protein kinase C. These findings could lead to new therapeutic approaches for inflammation management and the development of new drugs.