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Thromb Haemost 2009; 102(02): 336-346
DOI: 10.1160/TH09-01-0057
Platelets and Blood Cells
Schattauer GmbH

Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level Functional and modelling studies

Marilena Crescente
1   Research Laboratories, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Gisela Jessen
2   Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
,
Stefania Momi
3   Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Hans-Dieter Höltje
2   Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
,
Paolo Gresele
3   Department of Internal Medicine, Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Chiara Cerletti
1   Research Laboratories, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Giovanni de Gaetano
1   Research Laboratories, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
› Author AffiliationsFinancial support: This work was partially supported by the Italian Ministry of Research (MIUR, Programma Triennale Ricerca, decreto 1588) and the European Commission (FOOD-CT-2005, FLORA project, contract No. 007130).
Further Information

Publication History

Received: 22 January 2009

Accepted after major revision: 17 May 2009

Publication Date:
22 November 2017 (online)

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Summary

While resveratrol and quercetin possess antiplatelet activity, little is known on the effect of gallic acid on platelets.We studied the interactions of these three different polyphenols among themselves and with aspirin, at the level of platelet cyclooxygenase-1 (COX-1). Both functional (in vitro and in vivo) and molecular modelling approaches were used. All three polyphenols showed comparable antioxidant activity (arachidonic acid [AA]-induced intraplatelet ROS production); however, resveratrol and quercetin, but not gallic acid, inhibited AA-induced platelet aggregation. Gallic acid, similarly to salicylic acid, the major aspirin metabolite, prevented inhibition of AA-induced platelet function by aspirin but, at variance with salicylic acid, also prevented inhibition by the other two polyphenols. Molecular modelling studies, performed by in silico docking the polyphenols into the crystal structure of COX-1, suggested that all compounds form stable complexes into the COX-1 channel, with slightly different but functionally relevant interaction geometries. Experiments in mice showed that gallic acid administered before aspirin, resveratrol or quercetin fully prevented their inhibitory effect on serum TxB2. Finally, a mixture of resveratrol, quercetin and gallic acid, at relative concentrations similar to those contained in most red wines, did not inhibit platelet aggregation, but potentiated sub-inhibitory concentrations of aspirin. Gallic acid interactions with other polyphenols or aspirin at the level of platelet COX-1 might partly explain the complex,and possibly contrasting, effects of wine and other components of the Mediterranean diet on platelets and on the pharmacologic effect of lowdose aspirin.

Keywords

Platelets - aspirin - dietary polyphenols - COX-1 inhibition - fooddrug interaction
 

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