Inhibitory Effects Of Luteolin-4 '-O-Beta-D-Glucopyranoside On P2y(12) And Thromboxane A(2) Receptor-Mediated Amplification Of Platelet Activation In Vitro

Platelet activation and subsequent accumulation at sites of vascular injury are central to thrombus formation, which is considered to be a trigger of several cardiovascular diseases. Callicarpa nudiflora (C. nudiflora) Hook is a traditional Chinese medicinal herb for promoting blood circulation by removing blood stasis. In our previous study, several compounds extracted from this herb, including luteolin-4'-O-beta-D-glucopyranoside (LGP), were revealed to exert inhibitory effects on adenosine diphosphate (ADP)-induced platelet aggregation. The aim of present study was to confirm these antiplatelet effects and elucidate the potential mechanisms. Using a platelet-aggregation assay, it was revealed that LGP significantly inhibited platelet aggregation induced by ADP, U46619 and arachidonic acid. It was also found that LGP exhibited marked inhibitory effects on the activation of alpha(IIb)beta(3) integrin, the secretion of serotonin from granules, and the synthesis of thromboxane A(2). In addition, the results showed that LGP suppressed Ras homolog family member A and phosphoinositide 3-kinase/Akt/glycogen synthase kinase 3 beta signal transduction. Data from a radio-labeled ligand-binding assay indicated that LGP exhibited apparent competing effects on thromboxane receptor (TP) and P2Y(12) receptors. In conclusion, the data presented here demonstrated that LGP, a natural compound from C. nudiflora Hook, inhibited the development of platelet aggregation and amplification of platelet activation. These inhibitory effects may be associated with its dual-receptor inhibition on P2Y(12) and TP receptors.