Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid

In the present work, the vasorelaxant effect of dioclein, a new flavonoid isolated from Dioclea grandiflora (Leguminoseae), was investigated in the rat aorta. Dioclein induced a concentration-dependent relaxation in vessels pre-contracted with phenylephrine (IC 50=1.3±0.3 μM), a response which was abolished after endothelium removal. Neither indomethacin (10 μM), an inhibitor of cyclo-oxygenase, nor atropine (1 μM), an antagonist of muscarinic receptors, modified the effect of dioclein. Dioclein (30 μM) induced a significant increase in guanosine 3′:5′-cyclic monophosphate (cyclic GMP) levels in aortic rings with endothelium. The nitric oxide (NO) synthase inhibitor, N G-nitro- l-arginine-methyl-ester ( l-NAME, 300 μM), strongly inhibited or abolished the relaxing effect and rise in cyclic GMP levels induced by dioclein. Furthermore, dioclein (30 μM) had no effect on the endothelium-independent relaxation produced by the NO donor, 3-morpholino-sydnonimine (SIN-1), while superoxide dismutase (100 U ml −1) significantly potentiated it. These results indicate that, in the rat aorta, dioclein induces a NO- and endothelium-dependent vasorelaxant effect, which is associated with cyclic GMP elevation. This vasorelaxation likely results from enhanced synthesis of NO rather than enhanced biological activity of NO.