Sulforaphane attenuates platelet granule secretion through down-regulating glycoprotein VI-mediated p38 MAPK/cPLA(2) signaling pathway

Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and is important in mediating granule secretion and atherothrombosis. Sulforaphane (SFN), a dietary isothiocyanate enriched in cruciferous vegetables, exerts multiple biological activities. This study aimed to investigate the efficacy of SFN on GPVI-mediated signaling and platelet granule secretion in vitro. We herein demonstrated that SFN greatly attenuated granule secretion in human gel-filtered platelets in response to collagen, including inhibiting CD62P and CD63 expression and PF4, CCL5, and ATP release. Mechanistically, these inhibitory effects of SFN were mainly mediated by its attenuation of cytosolic phospholipase A(2) (cPLA(2)) phosphorylation and thromboxane A(2) (TxA(2)) generation. Moreover, SFN did not further decrease the inhibitory effects of p38 MAPK inhibitor SB203580 on cPLA(2) phosphorylation, TxA(2) generation and granule secretion. Thus, SFN attenuates platelet granule secretion via down-regulating GPVI-mediated p38 MAPK/cPLA(2)/TxA(2) signaling, which may play important preventive roles in cardiovascular diseases.