Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

The inhibitory mechanism of crude saponin fraction from Korean Red Ginseng in collagen-induced platelet aggregation

  • Jeon, Bo Ra (Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Su Jung (Department of Biomedical Laboratory Science, Daegu Health College) ;
  • Hong, Seung Bok (Department of Clinical Laboratory Science, Chungbuk Health and Science University) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering and Regional Research Center, Inje University) ;
  • Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Rhee, Man Hee (Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2015.01.20
  • Accepted : 2015.02.11
  • Published : 2015.07.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Korean Red Ginseng has been used as a traditional oriental medicine to treat illness and to promote health for several thousand years in Eastern Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major active ingredients responsible for Korean Red Ginseng's therapeutic activity against many kinds of illness. Although the crude saponin fraction (CSF) displayed antiplatelet activity, the molecular mechanism of its action remains to be elucidated. Methods: The platelet aggregation was induced by collagen, the ligand of integrin ${\alpha}_{II}{\beta}_I$ and glycoprotein VI. The crude saponin's effects on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate (ATP) release] were determined. The activation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3-kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of integrin ${\alpha}_{II}b{\beta}_{III}$ was examined by fluorocytometry. Results: CSF strongly inhibited collagen-induced platelet aggregation and ATP release in a concentration-dependent manner. It also markedly suppressed $[Ca^{2+}]_i$ mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly inhibited the fibrinogen binding to integrin ${\alpha}_{IIb}{\beta}_3$. Conclusion: Our present data suggest that CSF may have a strong antiplatelet property and it can be considered as a candidate with therapeutic potential for the treatment of cardiovascular disorders involving abnormal platelet function.

Keywords

References

  1. Schwartz SM, Heimark RL, Majesky MW. Developmental mechanisms underlying pathology of arteries. Physiol Rev 1990;70:1177-209. https://doi.org/10.1152/physrev.1990.70.4.1177
  2. Berridge MJ, Irvine RF. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 1984;312:315-21. https://doi.org/10.1038/312315a0
  3. Jennings LK. Role of platelets in atherothrombosis. Am J Cardiol 2009;103:4A-10A. https://doi.org/10.1016/S0002-9149(08)02058-4
  4. Pasqui AL, Capecchi PL, Ceccatelli L, Mazza S, Gistri A. Laghi Pasini F, Di Perri T. Nitroprusside in vitro inhibits platelet aggregation and intracellular calcium translocation. Effect of haemoglobin. Thromb Res 1991;61:113-22.
  5. Nishikawa M, Tanaka T, Hidaka H. $Ca^{2+}$-calmodulin-dependent phosphorylation and platelet secretion. Nature 1980;287:863-5. https://doi.org/10.1038/287863a0
  6. Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G. Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference onAntithrombotic and Thrombolytic Therapy.Chest 2004;126:234S-64S. https://doi.org/10.1378/chest.126.3_suppl.234S
  7. Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003;2:15-28. https://doi.org/10.1038/nrd985
  8. Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003;41:961-5. https://doi.org/10.1016/S0735-1097(02)03014-0
  9. Eisert WG. How to get from antiplatelet to antithrombotic treatment. Am J Ther 2001;8:443-9. https://doi.org/10.1097/00045391-200111000-00009
  10. Rezkalla SH, Benz M. Antiplatelet therapy from clinical trials to clinical practice. Clin Med Res 2003;1:101-4. https://doi.org/10.3121/cmr.1.2.101
  11. Hu FB. Plant-based foods and prevention of cardiovascular disease: an overview. Am J Clin Nutr 2003;78:544S-51S. https://doi.org/10.1093/ajcn/78.3.544S
  12. Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicineginseng (II): collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem 2009;16:2924-42. https://doi.org/10.2174/092986709788803204
  13. Kim SK, Park JH. Trends in ginseng research in 2010. J Ginseng Res 2011;35: 389-98. https://doi.org/10.5142/jgr.2011.35.4.389
  14. Kimura Y, Okuda H, Arichi S. Effects of various ginseng saponins on 5- hydroxytryptamine release and aggregation in human platelets. J Pharm Pharmacol 1988;40:838-43. https://doi.org/10.1111/j.2042-7158.1988.tb06285.x
  15. Kuo SC, Teng CM, Lee JC, Ko FN, Chen SC, Wu TS. Antiplatelet components in Panax ginseng. Planta Med 1990;56:164-7. https://doi.org/10.1055/s-2006-960916
  16. Lee WM, Kim SD, Park MH, Cho JY, Park HJ, Seo GS, Rhee MH. Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: critical roles of ERK2 and cAMP. J Pharm Pharmacol 2008;60:1531-6. https://doi.org/10.1211/jpp.60.11.0015
  17. Lee DH, Cho HJ, Kang HY, Rhee MH, Park HJ. Total saponin from Korean Red Ginseng inhibits thromboxane A2 production associated microsomal enzyme activity in platelets. J Ginseng Res 2012;36:40-6. https://doi.org/10.5142/jgr.2012.36.1.40
  18. Lee DH, Cho HJ, Kim HH, Rhee MH, Ryu JH, Park HJ. Inhibitory effects of total saponin from Korean Red Ginseng via vasodilator-stimulated phosphoprotein- Ser(157) phosphorylation on thrombin-induced platelet aggregation. J Ginseng Res 2013;37:176-86. https://doi.org/10.5142/jgr.2013.37.176
  19. Oh WJ, Endale M, Park SC, Cho JY, Rhee MH. Dual roles of quercetin in platelets: phosphoinositide-3-kinase and MAP kinases inhibition, and cAMPdependent vasodilator-stimulated phosphoprotein stimulation. Evid Based Complement Alternat Med 2012;2012:485262.
  20. Schaeffer J, Blaustein MP. Platelet free calcium concentrations measured with fura-2 are influenced by the transmembrane sodium gradient. Cell Calcium 1989;10:101-13. https://doi.org/10.1016/0143-4160(89)90050-X
  21. Park HJ, Lee JH, Song YB, Park KH. Effects of dietary supplementation of lipophilic fraction from Panax ginseng on cGMP and cAMP in rat platelets and on blood coagulation. Biol Pharm Bull 1996;19:1434-9. https://doi.org/10.1248/bpb.19.1434
  22. Jung KY, Kim DS, Oh SR, Lee IS, Lee JJ, Park JD, Kim SI, Lee HK. Platelet activating factor antagonist activity of ginsenosides. Biol Pharm Bull 1998;21:79-80. https://doi.org/10.1248/bpb.21.79
  23. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  24. Radad K, Gille G, Liu L, Rausch WD. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci 2006;100:175-86. https://doi.org/10.1254/jphs.CRJ05010X
  25. Israels SJ, Gerrard JM, Jacques YV, McNicol A, Cham B, Nishibori M, Bainton DF. Platelet dense granule membranes contain both granulophysin and P-selectin (GMP-140). Blood 1992;80:143-52.
  26. Unsworth AJ, Smith H, Gissen P, Watson SP, Pears CJ. Submaximal inhibition of protein kinase C restores ADP-induced dense granule secretion in platelets in the presence of $Ca^{2+}$. J Biol Chem 2011;286:21073-82. https://doi.org/10.1074/jbc.M110.187138
  27. Adam F, Kauskot A, Rosa JP, Bryckaert M. Mitogen-activated protein kinases in hemostasis and thrombosis. J Thromb Haemost 2008;6:2007-16. https://doi.org/10.1111/j.1538-7836.2008.03169.x
  28. Adam F, Kauskot A, Nurden P, Sulpice E, Hoylaerts MF, Davis RJ, Rosa JP, Bryckaert M. Platelet JNK1 is involved in secretion and thrombus formation. Blood 2010;115:4083-92. https://doi.org/10.1182/blood-2009-07-233932
  29. Calderwood DA. Integrin activation. J Cell Sci 2004;117:657-66. https://doi.org/10.1242/jcs.01014
  30. Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002;8:1227-34. https://doi.org/10.1038/nm1102-1227

Cited by

  1. Water soluble tomato concentrate regulates platelet function via the mitogen-activated protein kinase pathway vol.56, pp.2, 2015, https://doi.org/10.14405/kjvr.2016.56.2.67
  2. Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities vol.24, pp.6, 2015, https://doi.org/10.4062/biomolther.2016.027
  3. Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells vol.41, pp.3, 2015, https://doi.org/10.1016/j.jgr.2016.05.002
  4. Tomato Concentrates Inhibit Platelet Function and Thrombus Formation in Rats vol.17, pp.1, 2015, https://doi.org/10.3923/pjn.2018.25.33
  5. Eisenia bicyclis (brown alga) modulates platelet function and inhibits thrombus formation via impaired P2Y12 receptor signaling pathway vol.40, pp.None, 2015, https://doi.org/10.1016/j.phymed.2018.01.003
  6. Ginseng berry extract increases nitric oxide level in vascular endothelial cells and improves cGMP expression and blood circulation in muscle cells vol.22, pp.3, 2015, https://doi.org/10.20463/jenb.2018.0018
  7. Aqueous Extract of Taegeuk Ginseng Inhibits Platelet Aggregation and Thrombus Formation vol.21, pp.11, 2018, https://doi.org/10.1089/jmf.2017.4145
  8. Effect of Tea Dregs Form and Different Fermentation Process on the Nutrient, Tannin, Saponin, flavonoid content and Antioxidant Activity vol.18, pp.1, 2015, https://doi.org/10.3923/pjn.2019.25.33
  9. 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
  10. Prevention of platelet aggregation and arterial thrombosis using a modified Shenzhu Guanxin Formula vol.48, pp.10, 2015, https://doi.org/10.1177/0300060520941326
  11. Biofunctional properties of wild cultivated and cultivated Ginseng (Panax ginseng Meyer) extracts obtained using subcritical water extraction vol.56, pp.8, 2021, https://doi.org/10.1080/01496395.2020.1781893
  12. Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds vol.12, pp.9, 2015, https://doi.org/10.1039/d1md00100k