Bioactivity-guided fractionation of the dichloromethane and ethanol extracts from the aerial parts of Artemisia copa led to the isolation of the flavonoids spinacetin, jaceosidin, axillarin, penduletin, tricin and chrysoeriol. These compounds were studied for possible inhibitory activity on the generation of inflammatory mediators in a cell line of mouse macrophages (RAW 264.7) stimulated with lipopolysaccharide. Spinacetin and jaceosidin weakly inhibited nitric oxide production whereas all flavonoids reduced prostaglandin E2 levels to different extents. The most active flavonoid was jaceosidin that inhibited cyclooxygenase-2 activity in a concentration-dependent manner with an IC50 value of 2.8 microM. In addition, the other flavonoids partially inhibited synovial phospholipase A2 activity. These mechanisms may provide a basis for explaining the anti-inflammatory activity of this plant.