Abstract
AIM: 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. METHOD: 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. RESULT: The results indicated that dl-PHPB, puerarin and salvianolic acid B significantly inhibited platelet aggregation both in vivo and in vitro. In addition, the content of IP(3), cAMP and intracellular [Ca(2+)](i) were measured in HEK293 cell lines overexpressing P2Y(1) and P2Y(12). Dl-PHPB and puerarin could obviously reduce 2-MeSADP-induced IP(3) 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 [Ca(2+)](i) induced by 2-MeSADP; however, salvianolic acid B showed no effect on intracellular [Ca(2+)](i) elevation. CONCLUSION: These results suggested that dl-PHPB and puerarin inhibited platelet aggregation via targeting at P2Y(1) receptor and P2Y(1)-Gq-IP(3)-Ca(2+) signal pathway. Differently, salvianolic acid B inhibited platelet aggregation via targeting at P2Y(12) receptor and via Gi-AC-cAMP signal pathway.