Abstract:

Objective To investigate the protective effects of Sulforaphane （SFN） against high glucose （HG）?induced human platelet apoptosis and elucidate the underlying mechanisms in vitro. Methods Purified platelets obtained from healthy individuals were pre?incubated with various concentrations of SFN （5， 10， or 20 μmol/L） or a vehicle control （0.05% DMSO） for 40 minutes at 37 ℃. Subsequently， the platelets were stimulated with normal glucose （NG， 5 mmol/L） or high glucose （HG， 25 mmol/L） for an additional duration of 90 minutes. Flow cytometry was employed to assess platelet mitochondrial membrane potential depolarization （Δψm）， exposure of phosphatidylserine （PS）， and generation of total intraplatelet reactive oxygen species （ROS）. Phosphorylation levels of PI3K and Akt were determined using Western blot. Results Compared to NG?treated human platelets， HG significantly induced depolarization of platelet Δψm and exposure of PS （P < 0.001）. These effects of HG were markedly attenuated by various concentrations of SFN （P < 0.001）. Mechanistically， SFN down?regulated the phosphorylation levels of PI3K （P < 0.01） and Akt （P < 0.05）， which were increased by HG when compared to the vehicle control， and substantially reduced total intracellular ROS levels （P < 0.001）. The inhibitory effects of SFN on HG?induced phosphorylation of PI3K and Akt， as well as its efficacy on total intracellular ROS generation， Δψm depolarization， and PS exposure in HG?stimulated human platelets were completely reversed by a specific agonist for PI3K， 740 Y?P. Conclusions The current study demonstrates that SFN exerts a protective effect on platelet apoptosis induced by HG， potentially through the down?regulation of the PI3K/Akt?mediated pathway in human platelets in vitro. These findings suggest that SFN may hold promise for improving thrombosis in diabetes mellitus and related chronic metabolic diseases.

Key words: sulforaphane, high glucose, platelet, apoptosis, diabetes mellitus