Letter	Planta Med 2006; 72: 468-470 DOI: 10.1055/s-2005-916236
© Georg Thieme Verlag KG Stuttgart · New York
Inhibition of cGMP-Phosphodiesterase-5 By Biflavones of Ginkgo biloba
Mario Dell'Agli1, Germana V. Galli1, Enrica Bosisio1
1 Department of Pharmacological Sciences, Faculty of Pharmacy, Milan, Italy

Abstract

Ginkgo biloba dimeric flavonoids (GBDF) were shown to inhibit cAMP phosphodiesterase activity and to promote vasorelaxation. In particular, amentoflavone exhibited endothelium-dependent relaxation of rat aorta rings via enhanced generation and/or increased biological activity of nitric oxide, leading to elevated cGMP levels. The aim of this study was to investigate whether GBDF were able to inhibit cGMP-specific phosphodiesterase-5 (PDE5) as well. Human recombinant PDE5A1 was prepared by expression of the full-length cDNA of PDE5A1 in COS-7 cells. The PDE activity was determined in the presence of biflavones at 0.1 - 100 μM. All biflavones inhibited PDE5A1 in a concentration-dependent fashion, ginkgetin being the most potent (IC₅₀ = 0.59 μM). The ability to inhibit the enzyme followed this order: ginkgetin > bilobetin > sciadopitysin > amentoflavone > sequoiaflavone. These data suggest that GBDF could exert a vasodilating effect through a mechanism independent of NO release.