Total saponin from Korean Red Ginseng inhibits binding of adhesive proteins to glycoprotein IIb/IIIa via phosphorylation of VASP (Ser¹⁵⁷) and dephosphorylation of PI3K and Akt

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• 作者：Hyuk-Woo Kwon¹ ; ^☆ ; Jung-Hae Shin¹ ; ^☆ ; Hyun-Jeong Cho² ; Man Hee Rhee³ ; Hwa-Jin Park¹ ; ^{mlsjpark@inje.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：adhesive protein ; clot retraction ; PI3K/Akt ; total saponin from Korean Red Ginseng ; VASP (Ser157)
• 刊名：Journal of Ginseng Research
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：40
• 期：1
• 页码：76-85
• 全文大小：1349 K

文摘

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 (Ser¹⁵⁷), 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 (Ser¹⁵⁷) 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 (Ser¹⁵⁷). 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 [Ca²⁺]_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.