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

Fenglin Song; Yanna Zhu; Zhenyin Shi; Jinju Tian; Xiujuan Deng; Jing Ren; Marc C. Andrews; Heyu Ni; Wenhua Ling; Yan Yang

doi:10.1160/th13-12-1002

Thrombosis and Haemostasis, Table of Contents

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

¹Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China

²Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

,

Yanna Zhu

³Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

,

Zhenyin Shi

⁴Disease Control and Prevention Center of Gansu Province, Lanzhou, People’s Republic of China

,

Jinju Tian

¹Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China

²Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

,

Xiujuan Deng

¹Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China

²Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

,

Jing Ren

¹Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China

²Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

,

Marc C. Andrews

⁵Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada

⁶Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada

⁷Department of Physiology, University of Toronto, Toronto, Ontario, Canada

,

Heyu Ni

⁵Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada

⁶Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada

⁷Department of Physiology, University of Toronto, Toronto, Ontario, Canada

⁸Canadian Blood Services, Toronto, Ontario, Canada

⁹Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

¹⁰Department of Medicine, University of Toronto, Toronto, Ontario, Canada

,

Wenhua Ling

¹Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China

²Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

,

Yan Yang

¹Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, Guangzhou, People’s Republic of China

²Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China

› Author Affiliations

Abstract

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.

Keywords

Hypercholesterolaemia - platelet granule - anthocyanins - PI3K

Full Text

References

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