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 (IC 50 = 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.
|Titolo:||Inhibition of cGMP-phosphodiesterase-5 by biflavones of Ginkgo biloba|
|Autori interni:||BOSISIO, ENRICA ANGELA (Ultimo)|
DELL'AGLI, MARIO (Primo)
|Settore Scientifico Disciplinare:||Settore BIO/15 - Biologia Farmaceutica|
|Data di pubblicazione:||2006|
|Digital Object Identifier (DOI):||10.1055/s-2005-916236|
|Appare nelle tipologie:||01 - Articolo su periodico|