Plant Food Delphinidin-3-Glucoside Significantly Inhibits Platelet Activation and Thrombosis: Novel Protective Roles against Cardiovascular Diseases

Abstract

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.

Consumption of anthocyanin-rich Queen Garnet plum juice reduces platelet activation related thrombogenesis in healthy volunteers

“…The potential anti-thrombotic mechanism of anthocyanins was investigated by Yang et al (2012) using delphinidin-3-glucoside which has an identical chemical structure to cyanidin-3-glucoside, except an additional OH-group in 5′-position of the B-ring (Kay, Mazza, & Holub, 2005). The authors concluded that delphinidin-3-glucoside exhibits its antithrombotic activity via the inhibition of the expression of P-selectin, CD63 and CD40L, a down-regulation of active integrin αIIbβ3, attenuation of fibrinogen binding, and reduction in phosphorylation of adenosine monophosphate-activated protein kinase.…”

Effects of purified anthocyanin supplementation on platelet chemokines in hypocholesterolemic individuals: a randomized controlled trial

“…Our previous studies have shown that purified anthocyanin supplementation reduces the levels of inflammatory biological markers and improves serum lipids and endothelial function [30–32]. We have also found that anthocyanins significantly inhibit platelet activation, thrombosis, platelet hyperactivity [33, 34] and platelet granule secretion of molecules such as CCL5, β-TG and soluble P-selectin (sP-selectin), both in vitro and in vivo [35]. However, the effects of purified anthocyanin supplementation on most other platelet chemokines in patients with hypercholesterolemia have not yet been assessed.…”

Anthocyanin Cyanidin-3-Glucoside Attenuates Platelet Granule Release in Mice Fed High-Fat Diets

“…Intake of plants rich in phytochemicals is negatively associated with CVDs (12). Anthocyanins, one of the best-studied types of polyphenols, are abundant in various fruits and vegetables, such as black rice, grapes, berries, and red cabbage.…”

“…However, it is difficult to explain the biological mechanism of anthocyanins because food extracts usually contain an enormous variety of bioactive compounds. Our previous studies have shown that the anthocyanin delphinidin-3-glucoside (Dp-3-g, another component of anthocyanins) can inhibit platelet activation and aggregation in vitro (11,12,14). We have also reported that capsules containing an anthocyanin mixture can inhibit platelet granule secretion in the plasma of patients with hypercholesterolaemia (11).…”