nitroarginine and ipriflavone

Ipriflavone [CAS No.: 35212-22-7] is a novel drug used in the treatment of osteoporosis successfully. However, its mechanism of action has not been fully clarified yet. We investigated the effects of ipriflavone and its metabolites (I, II, III, V, VI, VII) on lipopolysaccharide (LPS)-induced nitric oxide (NO) release from RAW-264.7 mouse macrophage cells. Our data show that the LPS-induced NO release from RAW-264.7 cells was significantly inhibited by ipriflavone metabolite-III [7-isopropoxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one], [CAS No.: 97846-18-9] in a dose (3 x 10(-8)-10(-5) M)-dependent manner. Ipriflavone itself and its other metabolites had much lower inhibitory effect on the LPS-induced NO release from RAW-264.7 cells. The IC50-value of ipriflavone metabolite-III (1.0 x 10(-6) M) was between the IC50-values of the two reference compounds dexamethasone (4.0 x 10(-8) M) and NG-Nitro-L-arginine (L-NNA, 7.5 x 10(-5) M). Our finding suggests that some of the beneficial effects of ipriflavone in the treatment of osteoporosis might be mediated by its metabolite-III.

Topics: Animals; Bone Remodeling; Cell Line; Dexamethasone; Enzyme Inhibitors; Glucocorticoids; Isoflavones; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine