Thromb Haemost 2014; 112(05): 981-991
DOI: 10.1160/th13-12-1002
Platelets and Blood Cells
Schattauer GmbH

Plant food anthocyanins inhibit platelet granule secretion in hypercholesterolaemia: Involving the signalling pathway of PI3K–Akt

Fenglin Song
1  Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China
2  Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
,
Yanna Zhu
3  Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
,
Zhenyin Shi
4  Disease Control and Prevention Center of Gansu Province, Lanzhou, People’s Republic of China
,
Jinju Tian
1  Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China
2  Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
,
Xiujuan Deng
1  Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China
2  Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
,
Jing Ren
1  Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China
2  Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
,
Marc C. Andrews
5  Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada
6  Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada
7  Department of Physiology, University of Toronto, Toronto, Ontario, Canada
,
Heyu Ni
5  Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada
6  Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada
7  Department of Physiology, University of Toronto, Toronto, Ontario, Canada
8  Canadian Blood Services, Toronto, Ontario, Canada
9  Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
10  Department of Medicine, University of Toronto, Toronto, Ontario, Canada
,
Wenhua Ling
1  Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China
2  Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
,
Yan Yang
1  Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China
2  Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China
› Author Affiliations
Financial support: This work was supported by National Natural Science Foundation of China Research Grants (No. 81372978), the Fundamental Research Funds for the Central Universities of China (12ykpy12), Laboratory Funding of Sun Yat-Sen University (KF201213), National Natural Science Foundation of China Research Grants (No. 81302424), Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20130171120056), the Canadian Institutes of Health Research(MOP 119540), and the Heart and Stroke Foundation of Canada (Ontario). YY was a recipient of the Canadian Blood Services postdoctoral fellowship award.
Further Information

Publication History

Received: 09 December 2013

Accepted after major revision: 13 June 2014

Publication Date:
20 November 2017 (online)

Summary

Controlling platelet granule secretion has been considered an effective strategy to dampen thrombosis and prevent atherosclerosis. Anthocyanins are natural plant pigments and possess a wide range of biological activities, including cardiovascular protective activity. In the present study we explored the effects and the potential mechanisms of anthocyanins on platelet granule secretion in hypercholesterolemia. In a randomised, double-blind clinical trial, 150 hypercholesterolaemic individuals were treated with purified anthocyanins (320 mg/day) or placebo for 24 weeks. Anthocyanins consumption significantly reduced plasma levels of β-thromboglobulin (β-TG), soluble P-selectin, and of Regulated on Activation Normal T cell Expressed and Secreted (RANTES) as compared with the placebo. A minor reduction in platelet factor 4 (PF4) and transforming growth factor β1 (TGF-β1) levels were also observed. In in vitro experiments, we observed that purified anthocyanin mixture, as well as its two main anthocyanin components, delphinidin-3-glucoside (Dp-3-g) and cyanidin-3-glucoside (Cy-3g) directly inhibited platelet á-granule, dense granule, and lysosome secretion evaluated by P-selectin, RANTES, β-TG, PF4, TGF-β1, serotonin, ATP, and CD63 release. Further, anthocyanins inhibited platelet PI3K/Akt activation and consequently attenuated eNOS phosphorylation and cGMP production, thus interrupting MAPK activation. LY294002, a PI3K inhibitor, did not cause additional inhibitory efficacy, indicating that anthocyanin-induced effects may be involved in inhibition of the PI3K/Akt signalling pathway. These results provide evidence that by inhibiting platelet granule secretion, anthocyanins may be a potent cardioprotective agent.