DOI QR코드

DOI QR Code

20(S)-ginsenoside Rg3 inhibits glycoprotein IIb/IIIa activation in human platelets

  • Kwon, Hyuk-Woo (Department of Biomedical Laboratory Science, Far East University)
  • Received : 2018.06.21
  • Accepted : 2018.08.15
  • Published : 2018.09.29

Abstract

The Panax ginseng Mayer is used in conventional medicine in Asia owing to its preventing effects on thrombosis, hypertension, atherosclerosis, vasorelaxation and myocardial infarction. Because platelets are crucial mediators of cardiovascular diseases, many studies have investigated its functions. The previous study showed the antiplatelet effects of crude ginseng fraction and two of its components, ginsenoside Rg3 (20S and 20R). In addition, ginsenoside Rg3-enriched fraction shows an inhibitory effect on collagen-activated rat platelets. However, the mechanism underlying this effect remains unclear. Thus, I investigated the inhibitory action of ginsenoside Rg3 (20S, G-Rg3) on the regulation of signaling molecules involved in ${\alpha}IIb/{\beta}_3$ activation. I found that G-Rg3, in a cyclic AMP dependent manner, inhibited thrombin-induced activation of human platelets and affinity of fibrinogen and fibronectin with ${\alpha}IIb/{\beta}_3$. Thus, in the present study, G-Rg3 showed an inhibitory effect on glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) activation, suggesting its potential use for preventing platelet-mediated thrombotic disease.

Keywords

References

  1. Phillips DR, Nannizzi-Alaimo L, Prasad KS (2001) Beta3 tyrosine phosphorylation in alphaIIbbeta3 (platelet membrane GP IIb-IIIa) outside-in integrin signaling. Thromb Haemost 86: 246-258 https://doi.org/10.1055/s-0037-1616222
  2. Smolenski A (2012) Novel roles of cAMP/cGMP-dependent signaling in platelets. J Thromb Haemost 10: 167-176 https://doi.org/10.1111/j.1538-7836.2011.04576.x
  3. Laurent V, Loisel TP, Harbeck B, Wehman A, Grobe L, Jockusch BM, Wehland J, Gertler FB, Carlier MF (1999) Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. J Cell Biol 144:1245-1258 https://doi.org/10.1083/jcb.144.6.1245
  4. Sudo T, Ito H, Kimura Y (2003) Phosphorylation of the vasodilatorstimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 14:381-390 https://doi.org/10.1080/09537100310001598819
  5. Matsuda H, Kubo M, Tani T, Arichi S, Kitagawa I (1985) Pharmacological Study on Panax ginseng CA MEYER V.: Effects of Red Ginseng on the Experimental Disseminated Intravascular Coagulation (4). On Ginsenoside-Rg3, Rh1 and Rh2. The Japanese Society of Pharmacognosy 39: 123-125
  6. Lee SR, Park JH, Kim ND, Choi KJ (1997) Inhibitory effects of ginsenoside Rg3 on platelet aggregation and its mechanism of action. J Ginseng Res 21: 132-140
  7. Lee WM, Kim SD, Park MH, Cho JY, Park HJ, Seo GS, Rhee MH (2008) Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: critical roles of ERK2 and cAMP. J Pharm Pharmacol 60: 1531-1536 https://doi.org/10.1211/jpp.60.11.0015
  8. Jeong D, Irfan M, Kim SD, Kim S, Oh JH, Rhee MH (2017) Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation. J Ginseng Res 41: 548-555 https://doi.org/10.1016/j.jgr.2016.11.003
  9. Shin JH, Kwon HW, Cho HJ, Rhee MH, Park HJ (2015) Inhibitory effects of total saponin from Korean Red Ginseng on [Ca2+]i mobilization through phosphorylation of cyclic adenosine monophosphatedependent protein kinase catalytic subunit and inositol 1,4,5- trisphosphate receptor type I in human platelets. J Ginseng Res 39: 354-364 https://doi.org/10.1016/j.jgr.2015.03.006
  10. Smolenski A, Bachmann C, Reinhard K, Honig-Liedl P, Jarchau T, Hoschuetzky H, Walter U. (1998) Analysis and regulation of vasodilator-stimulated phosphoprotein serine239 phosphorylation in vitro and in intact cells using a phosphor specific monoclonal antibody. J Biol Chem 273: 20029-20035 https://doi.org/10.1074/jbc.273.32.20029
  11. Barragan P, Bouvier JL, Roquebert PO, Macaluso G, Commeau P, Comet B, Eigenthaler M (2003) Resistance to thienopyridines: Clinical detection of coronary stent thrombosis by monitoring of vasodilatorstimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 59: 295-302 https://doi.org/10.1002/ccd.10497
  12. Jackson SP (2011) Arterial thrombosis - insidious, unpredictable and deadly. Nature medicine 17: 1423-1436 https://doi.org/10.1038/nm.2515
  13. Jennings LK (2009) Role of platelets in atherothrombosis. Am J Cardiol 103: 4A-10A
  14. Zarbock A, Polanowska-Grabowska RK, Ley K (2007) Plateletneutrophil-interactions: linking hemostasis and inflammation. Blood reviews 21: 99-111 https://doi.org/10.1016/j.blre.2006.06.001
  15. Davi G, Patrono C (2007) Platelet activation and atherothrombosis. New Engl J Med 357: 2482-2494 https://doi.org/10.1056/NEJMra071014
  16. Lee DH, Cho HJ, Kim HH, Rhee MH, Ryu JH, Park HJ (2013) Inhibitory effects of total saponin from Korean red ginseng via vasodilator-stimulated phosphoprotein-Ser157 phosphorylation on thrombin-induced platelet aggregation. J Ginseng Res 37: 176-186 https://doi.org/10.5142/jgr.2013.37.176
  17. Kwon HW, Shin JH, Lee DH, Park HJ (2015) Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets. Evid-Based Compl Alt. doi:10.1155/2015/764906
  18. Law DA, DeGuzman FR, Heiser P, Ministri-Madrid K, Killeen N and Phillips DR (1999) Integrin cytoplasmic tyrosine motif is required for outside-in ${\alpha}IIb{\beta}3$ signalling and platelet function. Nature 401: 808-811 https://doi.org/10.1038/44599
  19. Estevez B, Shen B and Du X (2015) Targeting Integrin and Integrin Signaling in Treating Thrombosis. Aterioscl Throm Vas 35: 24-29 https://doi.org/10.1161/ATVBAHA.114.303411
  20. Endale M, Lee WM, Kamruzzaman SM, Kim SD, Park JY, Park MH, Park TY, Park HJ, Cho JY, Rhee MH (2012) Ginsenoside Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation. Br J Pharmacol 167: 109-127 https://doi.org/10.1111/j.1476-5381.2012.01967.x
  21. Lee JG, Lee YY, Kim SY, Pyo JS, Yun-Choi HS, Park JH (2009) Platelet antiaggregating activity of ginsenosides isolated from processed ginseng. Die Pharmazie-Int J Pharm Pharm Sci 64: 602-604
  22. Lee JG, Lee YY, Wu B, Kim SY, Lee YJ, Yun-Choi HS, Park JH (2010) Inhibitory activity of ginsenosides isolated from processed ginseng on platelet aggregation. Die Pharmazie-Int J Pharm Pharm Sci 65: 520-522
  23. Ju HK, Lee JG, Park MK, Park SJ, Lee CH, Park JH, Kwon SW (2012) Metabolomic investigation of the anti-platelet aggregation activity of ginsenoside Rk1 reveals attenuated 12-HETE production. J Proteome Res 11: 4939-4946 https://doi.org/10.1021/pr300454f

Cited by

  1. Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP3RI and VASP vol.62, pp.1, 2018, https://doi.org/10.3839/jabc.2019.014
  2. Anti-platelet role of Korean ginseng and ginsenosides in cardiovascular diseases vol.44, pp.1, 2018, https://doi.org/10.1016/j.jgr.2019.05.005
  3. The effects of ginsenosides on platelet aggregation and vascular intima in the treatment of cardiovascular diseases: From molecular mechanisms to clinical applications vol.159, pp.None, 2020, https://doi.org/10.1016/j.phrs.2020.105031
  4. Ginsenosides for cardiovascular diseases; update on pre-clinical and clinical evidence, pharmacological effects and the mechanisms of action vol.166, pp.None, 2021, https://doi.org/10.1016/j.phrs.2021.105481