Flavonoids are selective cyclic GMP phosphodiesterase inhibitors

Ruckstuhl, M.; Beretz, Alain; Anton, Robert; Landry, Yves

doi:10.1016/0006-2952(79)90249-1

Cited by 80 publications

(27 citation statements)

References 10 publications

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“…In the present paper, we found that chrysin increased cGMP vascular mesenteric accumulation only in vessels with intact endothelium, an effect which was suppressed by nitric oxide synthase inhibition with L-NAME. Several studies have shown that flavonoids, such as chrysin, can inhibit cyclic nucleotide phosphodiesterases, a family of enzymes involved in the breakdown of the vasorelaxant cyclic nucleotides [19, 20]. However, the increase in cGMP levels induced by chrysin seemed to be unrelated to the inhibition of cyclic nucleotide phosphodiesterases, since chrysin was unable to elevate cGMP levels in endothelium-denuded vascular mesenteric beds.…”

Section: Discussionmentioning

confidence: 99%

Effects of the Dietary Flavonoid Chrysin in Isolated Rat Mesenteric Vascular Bed

et al. 2004

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In the present study, the effects of the bioflavonoid chrysin (5,7-dihydroxyflavone) were analyzed on the perfusion pressure of isolated mesenteric vascular bed. The vasorelaxant effects of chrysin were more potent on intact endothelium than on denuded vessels. This endothelium-dependent response induced by chrysin was inhibited in the presence of N^G-nitro-L-arginine methyl ester (L-NAME), KCl, tetraethylammonium (TEA), BaCl₂, TEA plus L-NAME, and ouabain plus BaCl₂, while incubations with indomethacin and glibenclamide did not modify the response induced by this bioflavonoid. Neither gap junction inhibition with carbenoxolone nor epoxyeicosatrieconic acid synthesis inhibition with sulfaphenazole (selective CYP 2C/3A inhibitor) or 7-ethoxyresorufin (selective CYP 1A inhibitor) inhibited the chrysin-induced relaxation. Moreover, chrysin increased L-NAME-sensitive cGMP accumulation in intact vascular mesenteric preparation. In conclusion, chrysin shows vasodilator effects on resistance vessels, which depend partially on the functional endothelium and appear to be related to the NO/cGMP pathway and, possibly to the release of endothelium-derived hyperpolarizing factor.

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Section: Discussionmentioning

confidence: 99%

Effects of the Dietary Flavonoid Chrysin in Isolated Rat Mesenteric Vascular Bed

et al. 2004

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“…Kinetic and structure-activity studies suggested that these effects were attributable, at least in part, to competitive inhibition of substrate binding so that the cyclic nucleotides tended to accumulate. Quercetin (153) and catechin (152) were among the most active of the phosphodiesterase inhibitors tested by these authors. Beretz et al (153) showed that quercetin blocks the ADP-induced aggregation of washed human platelets in vitro and also potentiates the antiaggregatory effects of prostacyclin.…”

Section: Polyphenols and Platelet Aggregationmentioning

confidence: 97%

“…Early investigations on the biological effects of flavonoids indicated that they were quite potent inhibitors of cAMP phosphodiesterase (151) and of cGMP phosphodiesterase (152). Kinetic and structure-activity studies suggested that these effects were attributable, at least in part, to competitive inhibition of substrate binding so that the cyclic nucleotides tended to accumulate.…”

Section: Polyphenols and Platelet Aggregationmentioning

confidence: 98%

Wine as a biological fluid: History, production, and role in disease prevention

Soleas

Diamandis

Goldberg

1997

J. Clin. Lab. Anal.

586

202

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“…It must also be noted that DSCG is a highly selective inhibitor of cyclic GMP hydrolysis (Bergstrand, Kristofferson, Lundquist & Schurmann 1977;and Table 1) and has been previously shown to inhibit histamine release from mast cells but not from basophils (Assem & Mongar, 1970). The structure-activity-relationship of these different chromone-like compounds have recently been studied (Ruckstuhl, Beretz, Anton & Landry, 1979;Ruckstuhl & Landry, 1981 Kaliner et al (1972) and Kaliner (1977). These various observations led to the concept that increases in cyclic AMP reduce mediator release and increases in cyclic GMP enhance release.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cyclic Amp‐ and Cyclic Gmp‐phosphodiesterase Inhibitors on Immunological Release of Histamine and on Lung Contraction

Frossard¹,

Landry²,

Pauli³

et al. 1981

British J Pharmacology

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Cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP)‐ and cyclic guanosine 3′, 5′‐monophosphate (cyclic GMP)‐phosphodiesterase activities from rat lung were selectively inhibited by ZK 62711 and M & B 22948, respectively. Theophylline and papaverine inhibited both activities. Rat lung strips contracted by carbachol were relaxed by 4‐(3‐cyclopentyloxy‐4‐methoxyphenyl)‐2‐pyrrolidone (ZK 62711, EC25 = 7 × 10−8m) and 2‐O‐propoxyphenyl‐8‐azapurin‐6‐one (M&B 22948, EC25 = 5 × 10−7m) indicating relaxant properties of both cyclic AMP and cyclic GMP. The antigen‐induced histamine release from human basophils was inhibited by ZK 62711 (IC25 = 8 × 10−7m), whereas M&B 22948 had no effect. On the contrary, the release from rat mast cells was inhibited by M&B 22948 (IC25 = 10_6m), while ZK 62711 had no effect. These data show an inhibitory effect of cyclic AMP on histamine release to be involved with basophils, whereas cyclic GMP is predominantly involved with mast cells. It is suggested that the antianaphylactic properties of cyclic nucleotide phosphodiesterase inhibitors are mainly linked to the increase of cyclic GMP.

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Flavonoids are selective cyclic GMP phosphodiesterase inhibitors

Cited by 80 publications

References 10 publications

Effects of the Dietary Flavonoid Chrysin in Isolated Rat Mesenteric Vascular Bed

Effects of the Dietary Flavonoid Chrysin in Isolated Rat Mesenteric Vascular Bed

Wine as a biological fluid: History, production, and role in disease prevention

Effects of Cyclic Amp‐ and Cyclic Gmp‐phosphodiesterase Inhibitors on Immunological Release of Histamine and on Lung Contraction

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