Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway

Abstract

Summary. Background: The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation, including the antioxidant quercetin. Objectives: In this report we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. Methods: The effect of quercetin on platelet aggregation, intracellular calcium release, whole cell tyrosine phosphorylation and intracellular signaling events including tyrosine phosphorylation and kinase activity of proteins involved in the collagen-stimulated glycoprotein (GP) signaling pathway were investigated. Results: We report that quercetin inhibits collagen-stimulated whole cell protein tyrosine phosphorylation and intracellular mobilization of calcium, in a concentration-dependent manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor GPVI. This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor g-chain, Syk, LATand phospholipase Cg2. Inhibition of phosphorylation of the Fc receptor g-chain suggests that quercetin inhibits earlysignaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor g-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase was also inhibited by quercetin in a concentration-dependent manner, both in whole cells and in isolation. Conclusions: The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple componentsof the GPVI signaling pathway, and may begin to explain the proposed health benefits of high quercetin intake.

Antithrombotic potential of <i>Berberis calliobotrys</i> extract

“…In addition to this, antiplatelet effect of flavonoids has been reported (Pearson et al, 2002). Qurecetin a well known flavonoid blocks the glycoprotein pathway thus, inhibits the response of platelets to collagen (Hubbard et al, 2003). HPLC profile of butanolic fraction in current experiments showed the presence of qurecetin, ferulic acid, p-coumaric acid and caffeic acids, It could be proposed that antithrombotic effect of B. calliobotrys is possibly due to the presence of qurecetin and other active constituents, which is in accordance with the results of previous finding of Fuentes et al (2013) who linked the possible antithrombotic effect of tomato with the presence of chlorogenic, caffeic, ferrulic and pcoumaric acids.…”

Chronic Heavy Ethanol Consumption Is Associated with Decreased Platelet Aggregation in Rats

“…Accordingly, it was shown that beneficial effects of wine on cardiovascular health are greater if wine is associated with a healthy diet (Caimi et al 2003). Quercetin, a flavonoid present in the human diet, which is found in high levels in wine, has been shown to inhibit platelet aggregation and signaling (Hubbard et al 2003). Animal studies demonstrated that resveratrol; a phytoalexin found in red wine modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion (Hung et al 2002;Orallo et al 2002;Bradamante et al 2004).…”

Grape Seed Extracts Inhibit Platelet Aggregation by Inhibiting Protein Tyrosine Phosphatase

“…After collagen stimulation, increased tyrosine phosphorylation was observed on multiple signaling molecules; tyrosine phosphorylation was greatly inhibited in the presence of quercetin, which is consistent with previous reports (Figure 2A). 6,7 Resveratrol had no effects on protein tyrosine phosphorylation (Figure 2A). In marked contrast, both MBA and CS caused increases in basal levels of tyrosine phosphorylation in multiple proteins (Figure 2A).…”