Selective Inhibition of P2Y1 and P2Y12 Receptor Signal Pathways in Platelet Aggregation in Transgenic Cell Lines and Rats by Potassium 2-(1-Hydroxypentyl)-Benzoate, Puerarin and Salvianolic Acid B.

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Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB), puerarin and salvianolic acid B are three natural products or derivatives that can inhibit platelet aggregation. However, the mechanisms of dl-PHPB, puerarin and salvianolic acid B to inhibit platelet aggregation are still not clear. Here, 2-methylthioadenosine diphosphate (2-MeSADP) was used as an inducer to confirm the effects of three drugs on platelet aggregation and illustrate the corresponding mechanisms. The results indicated that dl-PHPB, puerarin and salvianolic acid B significantly inhibited platelet aggregation both invivo and invitro. In addition, the content of IP3, cAMP and intracellular [Ca2+]i were measured in HEK293 cell lines overexpressing P2Y1 and P2Y12. Dl-PHPB and puerarin could obviously reduce 2-MeSADP-induced IP3 increase, but salvianolic acid B showed no effects. Unlike dl-PHPB and puerarin, which had no effects on 2-MeSADP-induced cAMP decrease, salvianolic acid B significantly reversed the reduction of cAMP. Both dl-PHPB and puerarin could decrease the enhanced intracellular [Ca2+]i induced by 2-MeSADP; however, salvianolic acid B showed no effect on intracellular [Ca2+]i elevation. These results suggested that dl-PHPB and puerarin inhibited platelet aggregation via targeting at P2Y1 receptor and P2Y1-Gq-IP3-Ca2+ signal pathway. Differently, salvianolic acid B inhibited platelet aggregation via targeting at P2Y12 receptor and via Gi-AC-cAMP signal pathway.