Plant-derived compounds normalise platelet bioenergetics and function in hyperglycaemia

Background Polyphenols have been shown to decrease oxidative stress and modulate glycaemic response. Nevertheless, their effect on platelet bioenergetics and clot structure in diabetes and hyperglycaemia is unknown.

Objectives To investigate the effect of polyphenols on human platelet bioenergetics and its subsequent effect on clot structure in normo- vs acute hyperglycaemia in vitro.

Methods Four polyphenols (resveratrol, hesperetin, epigallocatechin gallate (EGCG) and quercetin) were selected for initial analysis. Healthy volunteers’ isolated platelets/PRP were treated with 5 or 25mM glucose, to represent normo- and acute hyperglycaemia, respectively. Platelet-derived reactive oxygen species (ROS), citrate synthase activity (mitochondrial density), mitochondrial calcium flux and mitochondrial respiration were performed following exposure to polyphenols (20μM, 1hr) to determine their effects on platelet bioenergetics. Procoagulant platelets (annexinV) and fibrin fiber density (Alexa Fluor-488 fibrinogen), were analysed by laser scanning confocal microscopy, while clot porosity was determined using PRP following exposure to polyphenols (20μM, 20min).

Results Acute hyperglycaemia increased ROS, mitochondrial calcium flux, maximal respiration, and procoagulant platelet number. Resveratrol, quercetin and EGCG reduced platelet ROS in normo- and acute hyperglycaemic conditions. Mitochondrial density was decreased by quercetin and EGCG in normoglycaemia. Resveratrol and EGCG reduced mitochondrial calcium flux in acute hyperglycaemia. Resveratrol also decreased procoagulant platelet number and attenuated oxygen consumption rate in normo- and acute hyperglycaemia. No effect of hyperglycaemia or polyphenols was observed on fibrin fiber density or clot pore size.

Conclusions Our results suggest polyphenols attenuate increased platelet activity stemming from hyperglycaemia and may benefit thrombosis preventative strategies in patients with diabetes.