Urolithin A has antiplatelet effects in contrast to its glucuronide, urolithin B, and isourolithin A.

INTRODUCTION

Consumption of dietary ellagitannins has been suggested to have protective effects against cardiovascular disease, likely due to the colonic formation of urolithins and their subsequent systemic absorption. Urolithins have been previously shown to possess vasodilatory and anti-inflammatory properties. In this study, it was examined whether urolithins (urolithin A, B, and isourolithin A) and two of their glucuronides (urolithin A 3-glucuronide, isourolithin A 3-glucuronide) can block platelet aggregation in humans.

METHODS

Seventeen healthy volunteers were included in this study. For the assessment of platelet aggregation, whole blood impedance aggregometry was utilized. Coagulation was examined using a semi-automatic coagulometer with mechanical clot detection. Acute toxicity was evaluated with a rat red blood cell lysis assay. For mechanistic studies, an ELISA-based commercial kit was used.

RESULTS

Urolithin A was a relatively potent antiplatelet drug with an IC50 of 3.7 ± 1.0 µM in arachidonic acid-triggered platelet aggregation. Further experiments demonstrated that it could also block platelet aggregation induced by collagen, platelet-activating factor, thrombin receptor activator peptide, adenosine diphosphate, and even dithiothreitol. The findings imply that urolithin A had an effect on the thromboxane A₂ pathway and possibly additional platelet-signalling pathway(s). Combination experiments documented that urolithin can improve the antiplatelet effect of acetylsalicylic acid.

CONCLUSION

Our observations suggest that urolithin A can be further investigated or used as a template for the development of antiplatelet drug(s). Additional pharmacokinetic, toxicological and efficacy studies are, however, required to confirm and quantify the extent of this effect in vivo.