Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of
anthocyanins in many plant foods. Although several
anthocyanin compounds have been reported to be protective against
cardiovascular diseases (CVDs), the direct effect of
anthocyanins on platelets, the key players in
atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several
thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced
thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited
thrombus growth in a
carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of
P-selectin, CD63,
CD40L, which reflect platelet α- and δ-granule release, and cytosol
protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active
integrin αIIbβ3 on platelets, and attenuated
fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between
fibrinogen and
integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of
adenosine monophosphate-activated
protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates
thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against
thrombosis and CVDs.