Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity

Abstract

Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX, and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose-treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associated with DM.