Resveratrol inhibits Ca2+ signals and aggregation of platelets

Mikio Marumo,Ichiro Wakabayashi,Kazumi Ekawa

doi:10.1186/s12199-020-00905-1

Mikio Marumo, Ichiro Wakabayashi + Show 1 more

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https://doi.org/10.1186/s12199-020-00905-1

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Abstract

BackgroundResveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca2+-related mechanism for the inhibitory action of resveratrol on platelet aggregation.MethodsCa2+ entry and subsequent aggregation of human platelets induced by different stimulants including thrombin, thapsigargin, and 1-oleoyl-2-acetylglycerol (OAG) were measured by the fluorescence method and light transmittance method, respectively. Each stimulant was added to a nominally Ca2+-free medium containing platelets, and then CaCl2 was added to the medium to induce Ca2+ influx into platelets.ResultsThapsigargin-induced Ca2+ entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 6.25 μM or higher concentrations, while OAG-induced Ca2+ entry and subsequent platelet aggregation were not affected by resveratrol at concentrations up to 50 μM. In the nominally Ca2+-free medium, thrombin induced a small transient increase in intracellular Ca2+ concentrations, which was attenuated in the presence of resveratrol at 12.5 μM or higher concentrations. Thrombin-induced Ca2+ entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 12.5 μM or higher concentrations.ConclusionsThe results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca2+ release from its stores and inhibiting store-operated Ca2+ influx into platelets.

Highlights

The French paradox is based on epidemiological evidence that the incidence of ischemic heart disease in France is relatively low among western countries despite the saturated fat-rich diet of French people [1]
Representative charts of measurement of platelet aggregation induced by different stimulants Representative recordings of platelet aggregation by thrombin, thapsigargin, and OAG are shown in Fig. 1a, b, and c, respectively
Pretreatment of platelets with resveratrol (12.5 μM) attenuated the aggregatory responses to CaCl2 in the presence of thrombin (Fig. 1a) and thapsigargin (Fig. 1b), while the response in the presence of OAG was not affected by resveratrol (Fig. 1c)

Summary

Introduction

The French paradox is based on epidemiological evidence that the incidence of ischemic heart disease in France is relatively low among western countries despite the saturated fat-rich diet of French people [1]. The French paradox is usually explained by the high consumption of wine, especially red wine, by French people [1]. Resveratrol, a non-flavonoid polyphenolic compound, is a stilbene derivative and is abundant in red wine [2]. Platelet aggregation is induced by stimulants that cause elevation of [Ca2+]i. There have been few studies in which. Resveratrol has been shown to inhibit platelet aggregation. The mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca2+-related mechanism for the inhibitory action of resveratrol on platelet aggregation

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