Inhibition of cGMP-phosphodiesterase-5 by biflavones of Ginkgo biloba.
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 microM. All biflavones inhibited PDE5A1 in a concentration-dependent fashion, ginkgetin being the most potent (IC50 = 0.59 microM). 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.
Department of Pharmacological Sciences, Faculty of Pharmacy, Milan, Italy. mario.dellagli@unimi.it
Mario
M
Dell'Agli
Germana V
GV
Galli
Enrica
E
Bosisio
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D044946:Biflavonoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020441:Ginkgo biloba; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D012867:Skin / Q000098:blood supply; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D044946:Biflavonoids; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D014665:Vasodilator Agents; D015106:3',5'-Cyclic-GMP Phosphodiesterases