Treatment with quercetin and 3′,4′-dihydroxyflavonol inhibits platelet function and reduces thrombus formation in vivo

Abstract

Flavonols are polyphenolic compounds with reported cardiovascular benefits and have been shown to exhibit antiplatelet properties in vitro. While some studies have shown inhibition of platelet aggregation following dietary supplementation with flavonol rich foods, few studies have assessed the ability of flavonols to inhibit platelet mediated thrombus generation in vivo. Furthermore, the duration of benefit and the influence of different dosing regimens remain unclear. In this study we investigate the ability of two structurally related flavonols; quercetin (Que) and 3',4'-dihydroxyflavonol (DiOHF) to inhibit platelet aggregation, platelet granule exocytosis and vessel occlusion in a well characterized mouse model of platelet mediated arterial thrombosis. We investigated the effect of a single 6 mg/kg intravenous bolus and daily 6 mg/kg intraperitoneal doses over seven consecutive days. Carotid artery blood flow after injury was better maintained in mice treated with both Que and DiOHF when compared to the vehicle for both dosage regimens. This improved blood flow corresponded to inhibition of platelet aggregation and platelet dense granule exocytosis following chemical stimulation of PAR4. We therefore provide evidence of inhibition of platelet-mediated arterial thrombosis by flavonols in vivo, and demonstrate that this effect persists for at least 24 h after the last intraperitoneal dose. These data suggest a potential clinical role for flavonols as anti-platelet therapy.

Polyphenols: Benefits to the Cardiovascular System in Health and in Aging

“…In ApoE deficient mice, a diet supplemented with Mulberry leaves (1%) reduced atherosclerotic lesions in the aorta by 40% as well as demonstrating a lag time in the onset of LDL oxidation [181]. Quercetin is also anti-atherosclerotic by inhibiting platelet aggregation [182]. In bovine aortic endothelial cells, treatment with mulberry leave extract inhibited the TNFα mediated activation of NFκB thereby repressing the inflammatory response, as well inhibiting the expression of LOX-1 [183].…”

Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy

“…The preparation of human platelets and aggregation assays were performed using standard protocols as described by us previously 15, 16 . Briefly, human blood was collected in 3.2% citrate containing vacutainers via venepuncture from healthy, aspirin-free individuals with informed consent in accordance with the methods approved by the University of Reading Research Ethics Committee.…”

“…Individuals who consume diets with low levels of saturated fatty acids together with a substantial amount of fruits and vegetables have been shown to have reduced development of CVD risks 13, 14 . In particular, a number of dietary flavonoids such as quercetin 15 , tangeretin 16 , nobiletin 17 , luteolin and apigenin have been shown to exhibit inhibitory effects in platelets by modulating diverse signalling cascades 18 . However, several challenges are associated with using dietary components for the prevention and treatment of diseases.…”

The flavonols quercetin and 3′,4′-dihydroxyflavonol reduce platelet function and delay thrombus formation in a model of type 1 diabetes

“…30 In brief, PRP aggregation was performed in the presence of 100 µg/mL fibrinogen and 1 mM CaCl 2 at 37°C with constant stirring (1000 r/min). Platelet aggregation baseline was set against murine PPP diluted 1:2 in RCD buffer pH 7.4.…”

“…29 Furthermore, we showed that the administration of Que or DiOHF at 6 mg/kg for seven consecutive days inhibits platelet function and reduces thrombus formation in a mouse model of plateletmediated arterial thrombosis. 30 Therefore, the aim of this study was to investigate the effects of Que or DiOHF on in vivo arterial thrombus formation in animal models with diabetes and study the effects on platelet function ex vivo.…”