*5.1. Anthocyanins*

The anthocyanins delphinidin-3-*O*-rutinoside, cyanidin-3-*O*-glucoside, cyanidin-3-*O*rutinoside, and malvidin-3-*O*-glucoside inhibit platelet aggregation [30,31,96,98,111,118] using TRAP-6, epinephrine, collagen, and ADP as agonists [30,96,98,101,109–111,116,118]. The effects were even greater in mixtures of these compounds, possibly due to the synergism of polyphenols and anthocyanins.

The use of pure chemical compounds in studies on platelet function is vital to elucidate the mechanism of antiplatelet action. Yan et al. determined the effects of delphinidin-3-*O*glucoside on platelet activation in both in vitro and in vivo models of thrombosis, concluding a dose-dependent antiplatelet effect in human platelet-rich plasma (PRP) and washed platelets, activated with collagen, ADP, and TRAP-6 [31]. Delphinidin-3-*O*-glucoside also inhibited the growth of the thrombus in mice and the exposure of P-selectin in the platelet membrane. Furthermore, the authors reported that this compound inhibited the phosphorylation of the adenosine-activated protein kinase (AMPK) [31]. The concentrations of anthocyanins used in the cited experiments were within the physiological levels and the pharmacological dose (0.5–50 μM) [30].

In the presence of anthocyanins, thrombus formation in mice and human in vivo perfusion chambers was reduced at low and high shear rates [31]. In a model of intravital microscopy thrombosis, anthocyanins prolonged the time for thrombus formation at a dose of 0.5 μM and delayed vessel occlusion significantly at 5 μM and 50 μM. The release of α and dense granules, the expression of P-selectin, the cluster of differentiation (CD) 63 (CD63), CD40L, and the secretion of the cytosolic proteins were observed. In addition, delphinidin-3- *O*-glucoside decreased the expression of the α2bβ<sup>3</sup> integrin. Overall, the cited study suggests that the daily consumption of anthocyanins may play a fundamental role in the protection against CVD, which could be related to the inhibition of platelet activity [31].
