title: 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.
authors.affiliation: Canadian Blood Services, Toronto, Ontario, Canada. yangyan3@mail.sysu.edu.cn
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhenyin
authors.initials: Z
authors.lastname: Shi
authors.forename: Adili
authors.initials: A
authors.lastname: Reheman
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Jin
authors.forename: Conglei
authors.initials: C
authors.lastname: Li
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
authors.forename: Marc C
authors.initials: MC
authors.lastname: Andrews
authors.forename: Pingguo
authors.initials: P
authors.lastname: Chen
authors.forename: Guangheng
authors.initials: G
authors.lastname: Zhu
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001760:Bleeding Time; D023201:CD40 Ligand / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D060149:Tetraspanin 30 / Q000378:metabolism; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D019007:P-Selectin; D060149:Tetraspanin 30; D023201:CD40 Ligand; C494120:delphinidin 3-O-glucopyranoside; D055372:AMP-Activated Protein Kinases