Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum

We have studied the effect of 5-O-demethylnobiletin (1) on both the inflammation of mouse ears induced by repeated application of 12-O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A(2) (PLA(2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity. Compound I reduced the oedema formation, cell infiltration, and tissue damage in the inflammation induced by TPA in mouse ears, along with the acute oedema induced by carrageenan in mouse paws and the acute PLA(2)-induced oedema in mouse paws. The flavone inhibited leukotriene 134 formation in rat neutrophils and elastase release in human neutrophils, but did not reduce the expression of cyclooxygenase-2 (COX-2) in murine RAW 264.7 macrophages. These experimental results suggest that 1 may act through a direct inhibition of 5-LOX, without affecting the expression of COX-2.