title: Total saponin from Korean Red Ginseng inhibits binding of adhesive proteins to glycoprotein IIb/IIIa via phosphorylation of VASP (Ser(157)) and dephosphorylation of PI3K and Akt.
abstract: BACKGROUND
  Binding of adhesive proteins (i.e., fibrinogen, fibronectin, vitronectin) to platelet integrin glycoprotein IIb/IIIa (αIIb/β3) by various agonists (thrombin, collagen, adenosine diphosphate) involve in strength of thrombus. This study was carried out to evaluate the antiplatelet effect of total saponin from Korean Red Ginseng (KRG-TS) by investigating whether KRG-TS inhibits thrombin-induced binding of fibrinogen and fibronectin to αIIb/β3.
  
  
  METHODS
  We investigated the effect of KRG-TS on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and dephosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, affecting binding of fibrinogen and fibronectin to αIIb/β3, and clot retraction.
  
  
  RESULTS
  KRG-TS had an antiplatelet effect by inhibiting the binding of fibrinogen and fibronectin to αIIb/β3 via phosphorylation of VASP (Ser(157)), and dephosphorylation of PI3K and Akt on thrombin-induced platelet aggregation. Moreover, A-kinase inhibitor Rp-8-Br-cyclic adenosine monophosphates (cAMPs) reduced KRG-TS-increased VASP (Ser(157)) phosphorylation, and increased KRG-TS-inhibited fibrinogen-, and fibronectin-binding to αIIb/β3. These findings indicate that KRG-TS interferes with the binding of fibrinogen and fibronectin to αIIb/β3 via cAMP-dependent phosphorylation of VASP (Ser(157)). In addition, KRG-TS decreased the rate of clot retraction, reflecting inhibition of αIIb/β3 activation. In this study, we clarified ginsenoside Ro (G-Ro) in KRG-TS inhibited thrombin-induced platelet aggregation via both inhibition of [Ca(2+)]i mobilization and increase of cAMP production.
  
  
  CONCLUSIONS
  These results strongly indicate that KRG-TS is a beneficial herbal substance inhibiting fibrinogen-, and fibronectin-binding to αIIb/β3, and clot retraction, and may prevent platelet αIIb/β3-mediated thrombotic disease. In addition, we demonstrate that G-Ro is a novel compound with antiplatelet characteristics of KRG-TS.
authors: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gyungnam, Republic of Korea.
authors: Hyuk-Woo
authors: HW
authors: Kwon
authors: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gyungnam, Republic of Korea.
authors: Jung-Hae
authors: JH
authors: Shin
authors: Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon, Republic of Korea.
authors: Hyun-Jeong
authors: HJ
authors: Cho
authors: Laboratory of Veterinary Physiology and Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors: Man Hee
authors: MH
authors: Rhee
authors: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gyungnam, Republic of Korea.
authors: Hwa-Jin
authors: HJ
authors: Park
keywords: PI3K/Akt; VASP (Ser157); adhesive protein; clot retraction; total saponin from Korean Red Ginseng