title: The inhibitory activity of ginsenoside Rp4 in adenosine diphosphate-induced platelet aggregation.
abstract: BACKGROUND
  Korean ginseng,Panax ginsengMeyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects ofP. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification.
  
  
  METHODS
  To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin αIIbβ3and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets.
  
  
  RESULTS
  G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin αIIbβ3by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-γ phosphorylations.
  
  
  CONCLUSIONS
  G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.
authors.affiliation: Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Son
authors.affiliation: Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Da-Hye
authors.initials: DH
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science, Inje University, Gimhae, Korea.
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Man-Hee
authors.initials: MH
authors.lastname: Rhee
keywords: MAPK; fibrinogen; ginsenoside Rp4; granule; platelet aggregation