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Quercitrin inhibits platelet activation in arterial thrombosis
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  • Hyun Ju Do,
  • Tae Woo Oh,
  • Jae-Han Jeon,
  • Kyungho Kim
Hyun Ju Do
Korea Institute of Oriental Medicine
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Tae Woo Oh
Korea Institute of Oriental Medicine
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Jae-Han Jeon
Kyungpook National University
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Kyungho Kim
Korea Institute of Oriental Medicine
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Abstract

Background and Purpose: The ingestion of flavonoids has been reported to be associated with reduced cardiovascular disease risk. Among flavonoids, quercitrin is the most common flavonoid in nature, and it exhibits anti-oxidant properties. However, it is unclear whether quercitrin plays a role in thrombogenesis. Experimental Approach: The anti-platelet effect of quercitrin was assessed using platelet aggregation, granule secretion, calcium mobilization, integrin activation, and western blot. Antithrombotic effect was determined in mouse using 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 adverse effects. Key Results: Quercitrin significantly impaired CRP- or U46619-induced platelet aggregation, granule secretion, ROS generation, and intracellular Ca2+ 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 GPVI- or U46619-mediated phosphorylation of PLC and PI3K signaling during platelet activation. Further, the anti-oxidant effect is derived from decreased phosphorylation of components of the TRAF4/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. Conclusions and Implications: Our results demonstrated that quercitrin could be an effective therapeutic agent for the treatment of thrombotic diseases.