Abstract

Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic antiplatelet agents by blunting platelet activation receptors via its antioxidant phenomenon. However, there is limited information on the anti-platelet activity of grain-derived polyphenols. The aim of the study is to evaluate the effects of sorghum extract (Shawaya short black 1 variety), an extract previously characterised for its high antioxidant activity and reduction of oxidative stress-related endothelial dysfunction, on platelet aggregation, platelet activation and PMP release. Whole blood samples collected from 18 healthy volunteers were treated with varying non-cytotoxic concentrations of polyphenol-rich black sorghum extract (BSE). Platelet aggregation study utilised 5 µg/mL collagen to target the GPVI pathway of thrombus formation whereas adenine phosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation assessed by flow cytometry. Procaspase-activating compound 1 (PAC-1) and P-selectin/CD62P were used to evaluate platelet activation- related conformational changes and degranulation respectively. PMPs were isolated from unstimulated platelets and quantified by size distribution and binding to CD42b. BSE treatment significantly reduced both collagen-induced platelet aggregation and circulatory PMP release at 40 µg/mL (p < 0.001) when compared to control. However, there was no significant impact of BSE on ADP-induced activation-dependent conformational change and degranulation of platelets. Results of this study suggest that phenolic rich BSE may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and PMP release.

Highlights

  • According to a World Health Organisation report, cardiovascular diseases accounted for an estimated 31% of deaths globally with majority being a result of stroke or heart attack [1,2]

  • Results of this study suggest that phenolic rich black sorghum extract (BSE) may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and platelet microparticles (PMPs) release

  • The several signalling pathways involved in platelet activation and thrombus formation include receptor-agonist pathways such as P2Y1/P2Y12-adenine phosphate (ADP), GPVI-collagen, PAR1-thrombin and the COX-1-thromboxane [5]

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Summary

Introduction

According to a World Health Organisation report, cardiovascular diseases accounted for an estimated 31% of deaths globally with majority being a result of stroke or heart attack [1,2]. Treatment involves blunting the activity of platelets using antiplatelet drugs. These drugs interfere with the thrombotic pathophysiology—wherein a rupture of an atherosclerotic plaque triggers platelet hyper-activation resulting in unwanted clot formation and occlusion of the blood vessel. The several signalling pathways involved in platelet activation and thrombus formation include receptor-agonist pathways such as P2Y1/P2Y12-ADP, GPVI-collagen, PAR1-thrombin and the COX-1-thromboxane [5]. An agonist such as collagen when exposed by atherosclerotic plaque may Nutrients 2020, 12, 1760; doi:10.3390/nu12061760 www.mdpi.com/journal/nutrients

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