Quercitrin inhibits platelet activation in arterial thrombosis

• Published in: Phytomedicine (Stuttgart) 2021-01, Vol.80, p.153363, Article 153363
• Main Authors: Oh, Tae Woo, Do, Hyun Ju, Jeon, Jae-Han, Kim, Kyungho
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Arteries; Calcium - metabolism; Dose-Response Relationship, Drug; Fibrinolytic Agents - pharmacology; Flavonoids; Glycoprotein VI; Hemostasis - drug effects; Humans; Male; Mice; Mice, Inbred C57BL; Phosphorylation - drug effects; Platelet; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Platelet Membrane Glycoproteins - metabolism; Quercetin - adverse effects; Quercetin - analogs & derivatives; Quercetin - pharmacology; Quercitrin; Reperfusion Injury - chemically induced; Thrombosis; Thrombosis - chemically induced; Thrombosis - drug therapy; Thrombosis - metabolism
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2020.153363

The ingestion of flavonoids has been reported to be associated with reduced cardiovascular disease risk. Quercitrin is a common flavonoid in nature, and it exhibits antioxidant properties. Although the process of thrombogenesis is intimately related to cardiovascular disease risk, it is unclear whether quercitrin plays a role in thrombogenesis. The aim of this study was to examine the antiplatelet effect of quercitrin in platelet activation. Platelet aggregation, granule secretion, calcium mobilization, and integrin activation were used to assess the antiplatelet activity of quercitrin. Antithrombotic effect was determined in mouse using ferric chloride (FeCl3)-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro. Transection tail bleeding time was used to evaluate whether quercitrin inhibited primary hemostasis. Quercitrin significantly impaired collagen-related peptide-induced platelet aggregation, granule secretion, reactive oxygen species generation, and intracellular calcium mobilization. Outside-in signaling of αIIbβ3 integrin was significantly inhibited by quercitrin in a concentration-dependent manner. The inhibitory effect of quercitrin resulted from inhibition of the glycoprotein VI-mediated platelet signal transduction during cell activation. Further, the antioxidant effect is derived from decreased phosphorylation of components of the TNF receptor-associated factor 4/p47phox/Hic5 axis signalosome. Oral administration of quercitrin efficiently blocked FeCl3-induced arterial thrombus formation in vivo and thrombus formation on collagen-coated surfaces under arteriolar shear in vitro, without prolonging bleeding time. Studies using a mouse model of ischemia/reperfusion-induced stroke indicated that treatment with quercitrin reduced the infarct volume in stroke. Our results demonstrated that quercitrin could be an effective therapeutic agent for the treatment of thrombotic diseases.