Biol. Pharm. Bull. 28(8) 1366—1370 (2005)

activity in vitro and in vivo. The several action mechanisms have been proposed to explain their in vivo anti-inflammatory activity. Many flavonoids exert anti-oxidative and free radical scavenging activities. Some derivatives modulate cellular activities of the inflammation-associated cells such as mast cells and lymphocytes. In particular, varieties of flavonoid derivatives including quercetin inhibit the activity of arachidonic acid (AA)-metabolizing enzymes; phospholipase A2 (PLA2), cyclooxygenases (COX) and/or lipoxygenases (LOX). Recent investigations have also proved that certain flavonoids, especially flavone derivatives, have capacity to down-regulate proinflammatory enzyme expression such as COX-2 (an inducible isoform of COX) and inducible nitric oxide synthase (iNOS). Since the reaction products of these proinflammatory enzymes including prostaglandins (PG) and NO are crucially involved in inflammation, several attempts have been made to derive the optimal chemical structures of flavonoids showing significant inhibition of these proinflammatory enzyme activity and/or expression. For instance, various flavone derivatives have been synthesized and their inhibitory activity of PGE2 production from bacterial lipopolysaccharide (LPS)-treated macrophages were compared in order to find flavonoids acting on PLA2 and/or COX-2. Through this screening procedure, 2 ,4 ,7trimethoxyflavone (TMF) was found to possess a potent inhibitory activity of PGE2 production. Therefore, in the present investigation, this compound is selected for further pharmacological study and cellular action mechanism is elucidated. In vivo anti-inflammatory activity is also studied to examine the potential as new anti-inflammatory agent.