Inhibition of platelet-mediated arterial thrombosis and platelet granule exocytosis by 3′,4′-dihydroxyflavonol and quercetin

Abstract

Flavonols are polyphenolic compounds with broad-spectrum kinase inhibitory, as well as potent anti-oxidant and anti-inflammatory properties. Anti-platelet potential of quercetin (Que) and several related flavonoids have been reported; however, few studies have assessed the ability of flavonols to inhibit exocytosis of different platelet granules or to inhibit thrombus formation in vivo. 3',4'-Dihydroxyflavonol (DiOHF) is a flavonol which is structurally related to Que and has been shown to have greater anti-oxidant capacity and to improve the endothelial function in the context of diabetes and ischaemia/reperfusion injury. While the structural similarity to Que suggests DiOHF may have a potential to inhibit platelet function, no studies have assessed the anti-platelet potential of DiOHF. We therefore investigated platelet granule inhibition and potential to delay arterial thrombosis by Que and DiOHF. Both Que and DiOHF showed inhibition of collagen, adenosine diphosphate and arachidonic acid stimulated platelet aggregation, agonist-induced GPIIb/IIIa activation as demonstrated by PAC-1 and fibrinogen binding. While both flavonols inhibited agonist-induced granule exocytosis, greater inhibition of dense granule exocytosis occurred with DiOHF as measured by both ATP release and flow cytometry. In contrast, while Que inhibited agonist-induced P-selectin expression, as measured by both platelet surface P-selectin expression and upregulation of surface GPIIIa expression, inhibition by DiOHF was not significant for either parameter. C57BL/6 mice treated with 6 mg kg(-1) IV Que or DiOHF maintained greater blood flow following FeCl3-induced carotid artery injury when compared to the vehicle control. We provide evidence that Que and DiOHF improve blood flow following arterial injury in part by attenuating platelet granule exocytosis.

Comparative Effect of Quercetin and Quercetin‐3‐O‐β‐d‐Glucoside on Fibrin Polymers, Blood Clots, and in Rodent Models

“…including in vitro platelet activation, in vivo thrombosis inhibition [21][22][23][24] and human interventional studies on CVDs [25][26][27][28] of quercetin, and in vitro platelet activation inhibition [29] of quercetin-3-O-β-D-glucoside have been reported in dozens of research papers, few or no reports exist on the in vitro actions of quercetin and quercetin-3-O-β-D-glucoside on procoagulant proteinases, fibrin polymer formation, and blood clot, the in vitro and ex vivo anticoagulation actions of quercetin and quercetin-3-O-β-D-glucoside, or the in vivo effects of quercetin and quercetin-3-O-β-D-glucoside against arterial thrombosis and acute thromboembolism models and platelet activation.…”

Quercetin – a flavonoid with a high health-promoting potential

“…On the other hand, the research conducted by Raghavendra and Akhilender Naidu (2009) proved that 100 µM concentration of quercetin would cause only 1.7% inhibition of thrombocytes aggregation. Then, the results of other investigations delivered the data which indicate that 100 µM concentration of quercetin causes more than 90% inhibition of collagen-induced thrombocytes aggregation (Mosawy et al, 2013). The available results of other investigations confirm the antiplatelet efficiency of quercetin against the processes of aggregation induced by antagonists of platelets other than collagen.…”

“…The available results of other investigations confirm the antiplatelet efficiency of quercetin against the processes of aggregation induced by antagonists of platelets other than collagen. The experiment conducted by Mosawy et al (2013), found out that full inhibition of arachidonic acid induced platelet aggregation was achieved at 200 µM level of quercetin concentration. It was also proved that quercetin causes adenosine diphosphate (ADP) and epinephrine induced platelet aggregation (Islam et al, 2014).…”

Relationship between monocyte-platelet aggregation and endothelial function in middle-aged and elderly adults

“…; Mosawy et al. ). Platelet function was interrogated in venous blood samples with multiple outcomes (i.e., MPAs, PAC‐1 and anti‐CD62P binding), with and without canonical platelet agonists, using sophisticated and established flow cytometry techniques (Linden ) which have been associated with cardiovascular outcome.…”