TY - JOUR
T1 - The phytoestrogen 8-prenylnaringenin inhibits agonist-dependent activation of human platelets
AU - Di Vito, Clara
AU - Bertoni, Alessandra
AU - Nalin, Michela
AU - Sampietro, Sara
AU - Zanfa, Manuela
AU - Sinigaglia, Fabiola
N1 - Funding Information:
The authors thank Prof G. Appendino (University of Piemonte Orientale A. Avogadro, Italy) for providing 8-PN and Prof. M.E. Tira (University of Pavia, Italy) for the generous gift of type I collagen. This work was supported by grants from Ministero dell'Università e della Ricerca‐PRIN 2007 (to FS), from Regione Piemonte‐Ricerca Sanitaria Finalizzata 2006, 2008, 2009 and ‐Ricerca Scientifica Applicata 2004 , and from Università del Piemonte Orientale‐Ricerca Locale .
PY - 2012/11
Y1 - 2012/11
N2 - Background: Phytoestrogens are plant-derived polyphenolic compounds that exert beneficial effects on human health, mostly related to their estrogen mimetic activity. In particular a strong correlation between phytoestrogens intake and a lower risk of cardiovascular diseases has been reported. The flavanone 8-prenylnaringenin, extracted from hop flowers, has been identified as a novel phytoestrogen, unique with respect to estrogen receptors specificity and potency. However, to date no investigations on the 8-prenylnaringenin role in modulating platelet function have been undertaken. Methods: We evaluated the effect of 8-prenylnaringenin on platelet aggregation, intracellular calcium mobilization and protein phosphorylation triggered by thrombin and collagen, and platelet adhesion and dense granule secretion triggered by collagen. Results: 8-Prenylnaringenin inhibited platelet aggregation induced by different agonists and platelet adhesion to collagen matrix. 8-Prenylnaringenin directly increased intracellular cAMP and cGMP levels and thus promoted VASP phosphorylation. However, these molecular events were not responsible for the inhibitory action of 8-prenylnaringenin on platelets. Moreover, 8-prenylnaringenin inhibited the phosphorylation of Pyk2, Akt, and ERK1/2. Finally, 8-prenylnaringenin suppressed the mobilization of calcium and the secretion of dense granules. All these effects were independent of estrogen receptors recruitment. Conclusions: 8-Prenylnaringenin exerted anti-aggregatory and anti-adhesive effects on human platelets, independently of estrogen receptors, acting as an inhibitor of multiple proteins essential for the morphological and biochemical transformations that occur during platelet activation and aggregation. General significance: 8-Prenylnaringenin may represent a useful tool in the therapy and prevention of vascular diseases associated with platelet aggregation, such as atherosclerosis, myocardial infarction, coronary artery disease, and thrombosis.
AB - Background: Phytoestrogens are plant-derived polyphenolic compounds that exert beneficial effects on human health, mostly related to their estrogen mimetic activity. In particular a strong correlation between phytoestrogens intake and a lower risk of cardiovascular diseases has been reported. The flavanone 8-prenylnaringenin, extracted from hop flowers, has been identified as a novel phytoestrogen, unique with respect to estrogen receptors specificity and potency. However, to date no investigations on the 8-prenylnaringenin role in modulating platelet function have been undertaken. Methods: We evaluated the effect of 8-prenylnaringenin on platelet aggregation, intracellular calcium mobilization and protein phosphorylation triggered by thrombin and collagen, and platelet adhesion and dense granule secretion triggered by collagen. Results: 8-Prenylnaringenin inhibited platelet aggregation induced by different agonists and platelet adhesion to collagen matrix. 8-Prenylnaringenin directly increased intracellular cAMP and cGMP levels and thus promoted VASP phosphorylation. However, these molecular events were not responsible for the inhibitory action of 8-prenylnaringenin on platelets. Moreover, 8-prenylnaringenin inhibited the phosphorylation of Pyk2, Akt, and ERK1/2. Finally, 8-prenylnaringenin suppressed the mobilization of calcium and the secretion of dense granules. All these effects were independent of estrogen receptors recruitment. Conclusions: 8-Prenylnaringenin exerted anti-aggregatory and anti-adhesive effects on human platelets, independently of estrogen receptors, acting as an inhibitor of multiple proteins essential for the morphological and biochemical transformations that occur during platelet activation and aggregation. General significance: 8-Prenylnaringenin may represent a useful tool in the therapy and prevention of vascular diseases associated with platelet aggregation, such as atherosclerosis, myocardial infarction, coronary artery disease, and thrombosis.
KW - 8-Prenylnaringenin
KW - Collagen
KW - Cyclic nucleotides
KW - Platelets
KW - Signal transduction
KW - Thrombin
UR - http://www.scopus.com/inward/record.url?scp=84864762802&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2012.06.018
DO - 10.1016/j.bbagen.2012.06.018
M3 - Article
SN - 0304-4165
VL - 1820
SP - 1724
EP - 1733
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 11
ER -