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J Ginseng Res. 2016 Jan;40(1):76-85. doi: 10.1016/j.jgr.2015.05.004. Epub 2015 May 21.

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.

Journal of ginseng research

Hyuk-Woo Kwon, Jung-Hae Shin, Hyun-Jeong Cho, Man Hee Rhee, Hwa-Jin Park

Affiliations

  1. Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gyungnam, Republic of Korea.
  2. Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon, Republic of Korea.
  3. Laboratory of Veterinary Physiology and Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu, Republic of Korea.

PMID: 26843825 PMCID: PMC4703804 DOI: 10.1016/j.jgr.2015.05.004

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.

CONCLUSION: 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.

Keywords: PI3K/Akt; VASP (Ser157); adhesive protein; clot retraction; total saponin from Korean Red Ginseng

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