Antiplatelet activity of flavonoid and coumarin drugs.
Polyphenols are used as phlebotonic drugs, but their mechanism of action remains unknown. Since platelet activity and platelet-endothelial cell interactions are involved in the pathogenesis of cardiovascular disease, this work examines whether different flavonoid and coumarin drugs are able to inhibit platelet aggregation. This specific case of coumarins, the antiplatelet effect is not linked with a possible interaction over blood coagulation since this effect only dicoumarols have it. The antiplatelet capacity of polyphenols was assayed using peripheral blood platelets from healthy controls. The distribution of the different platelets subsets was quantified by flow cytometry, using the calcium ionophore as a pro-aggregant. The number of GPIIb/IIIa receptors occupied by the drugs was assayed by flow cytometry using two CD61 surface fluorescein antibodies. All the polyphenols tested inhibited platelet aggregation. A percentage antiplatelet activity of 88.91±7.98% was recorded for naringin, 48.43±8.84% for naringenin, 53.83±7.87% for esculetin, 54.65±6.91% for fraxetin, and 25.75±4.12% for coumarin. Naringin showed significantly greater percentage occupation of GPIIb/IIIa receptors than did naringenin (14.82±0.81% vs. 3.90±0.55%), and esculetin returned significantly higher values than fraxetin and coumarin (12.47±0.97 vs. 7.53±0.49 and 7.90±0.69 respectively). All drugs show important antiplatelet activity. Naringin was the best antiplatelet compound, showing the greatest antiplatelet activity and the highest percentage binding of GPIIb/IIIa receptors. However, any of the compounds used could be used in the prevention of cardiovascular disease.
Biomedical Sciences Department, Pharmacology Unit, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain. Electronic address: cristina.zaragoza@uah.es.
Cristina
C
Zaragozá
Laboratory of Immune System Diseases and Oncology, Department of Medicine and Medical Specialties, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain. Electronic address: jorge.monserrat@uah.es.
Jorge
J
Monserrat
Biomedical Sciences Department, Pharmacology Unit, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain. Electronic address: carolina.mantecon@gmail.com.
Carolina
C
Mantecón
Biomedical Sciences Department, Pharmacology Unit, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain. Electronic address: lucinda.villaescusa@uah.es.
Lucinda
L
Villaescusa
Biomedical Sciences Department, Pharmacology Unit, University of Alcalá, Alcalá de Henares, 28871 Madrid, Spain. Electronic address: francisco.zaragoza@uah.es.
Francisco
F
Zaragozá
Laboratory of Immune System Diseases and Oncology, Department of Medicine and Medical Specialties, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain; Immune System Diseases and Oncology Service, University Hospital "Príncipe de Asturias", Alcalá de Henares, 28871 Madrid, Spain. Electronic address: mademons@gmail.com.
Melchor
M
Álvarez-Mon
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D055815:Young Adult
D003374:Coumarins; D005419:Flavonoids; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D059808:Polyphenols
Coumarin; Flavonoid; Flow cytometry; GPIIb/IIIa; Platelet