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Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets

Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly redu...

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Autores principales: Bijak, Michal, Szelenberger, Rafal, Dziedzic, Angela, Saluk-Bijak, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017715/
https://www.ncbi.nlm.nih.gov/pubmed/29439388
http://dx.doi.org/10.3390/molecules23020374
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author Bijak, Michal
Szelenberger, Rafal
Dziedzic, Angela
Saluk-Bijak, Joanna
author_facet Bijak, Michal
Szelenberger, Rafal
Dziedzic, Angela
Saluk-Bijak, Joanna
author_sort Bijak, Michal
collection PubMed
description Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets’ aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets’ ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet activation.
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spelling pubmed-60177152018-11-13 Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets Bijak, Michal Szelenberger, Rafal Dziedzic, Angela Saluk-Bijak, Joanna Molecules Article Adenosine diphosphate (ADP) is the major platelet agonist, which is important in the shape changes, stability, and growth of the thrombus. Platelet activation by ADP is associated with the G protein-coupled receptors P2Y1 and P2Y12. The pharmacologic blockade of the P2Y12 receptor significantly reduces the risk of peripheral artery disease, myocardial infarction, ischemic stroke, and vascular death. Recent studies demonstrated the inhibition of ADP-induced blood platelet activation by three major compounds of the flavonolignans group: silybin, silychristin, and silydianin. For this reason, the aim of the current work was to verify the effects of silybin, silychristin, and silydianin on ADP-induced physiological platelets responses, as well as mechanisms of P2Y12-dependent intracellular signal transduction. We evaluated the effect of tested flavonolignans on ADP-induced blood platelets’ aggregation in platelet-rich plasma (PRP) (using light transmission aggregometry), adhesion to fibrinogen (using the static method), and the secretion of PF-4 (using the ELISA method). Additionally, using the double labeled flow cytometry method, we estimated platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. We demonstrated a dose-dependent reduction of blood platelets’ ability to perform ADP-induced aggregation, adhere to fibrinogen, and secrete PF-4 in samples treated with flavonolignans. Additionally, we observed that all of the tested flavonolignans were able to increase VASP phosphorylation in blood platelets samples, which is correlated with P2Y12 receptor inhibition. All of these analyses show that silychristin and silybin have the strongest inhibitory effect on blood platelet activation by ADP, while silydianin also inhibits the ADP pathway, but to a lesser extent. The results obtained in this study clearly demonstrate that silybin, silychristin, and silydianin have inhibitory properties against the P2Y12 receptor and block ADP-induced blood platelet activation. MDPI 2018-02-10 /pmc/articles/PMC6017715/ /pubmed/29439388 http://dx.doi.org/10.3390/molecules23020374 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bijak, Michal
Szelenberger, Rafal
Dziedzic, Angela
Saluk-Bijak, Joanna
Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets
title Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets
title_full Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets
title_fullStr Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets
title_full_unstemmed Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets
title_short Inhibitory Effect of Flavonolignans on the P2Y12 Pathway in Blood Platelets
title_sort inhibitory effect of flavonolignans on the p2y12 pathway in blood platelets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017715/
https://www.ncbi.nlm.nih.gov/pubmed/29439388
http://dx.doi.org/10.3390/molecules23020374
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