Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Spinach Saponin-Enriched Fraction Inhibits Platelet Aggregation in cAMP- and cGMP-Dependent Manner by Decreasing TXA2 Production and Blood Coagulation

  • Cho, Hyun-Jeong (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University) ;
  • Choi, Sun-A (Department of Biomedical Laboratory Science, College of Biomedical Science, Inje University) ;
  • Kim, Chun-Gyu (Department of Pharmaceutical Engineering, College of Engineering, Inje University) ;
  • Jung, Tae-Sung (Department of Pharmacy, Kungsung University) ;
  • Hong, Jeong-Hwa (School of Food and Life Science, College of Biomedical Science and Engineering, Inje University) ;
  • Rhee, Man-Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Park, Hye-Jin (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science, Inje University)
  • Received : 2010.09.27
  • Accepted : 2010.12.29
  • Published : 2011.04.30
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Abstract

In this study, we investigated the effect of spinach saponin-enriched fraction (SSEF) on collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation. SSEF inhibited collagen-induced platelet aggregation, and which was involved in the inhibition of thromboxane $A_2$ ($TXA_2$) production, an intracellular $Ca^{2+}$-agonist as an aggregation-inducing autacoidal molecule. In addition, SSEF significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonists as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that SSEF might inhibit $Ca^{2+}$-elevation and $TXA_2$ formation by increasing the production of $Ca^{2+}$-antagonistic molecules cAMP and cGMP. These mean that SSEF is a potent inhibitor of collagen-stimulated platelet aggregation. On the other hand, prothrombin time (PT) and activated partial thromboplastin time (APTT) were potently prolonged by SSEF. These findings suggest that SSEF prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that SSEF may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.

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References

  1. Afolayan, A. J. and Jimoh, F. O. (2009) Nutritional quality of some wild leafy vegetables in South Africa. Intl. J. Food Sci. Nutr. 60, 424-431. https://doi.org/10.1080/09637480701777928
  2. Akoum, A., Josefonvicz, J. and Sigot, M. (1990). Anticoagulant activity of a bacterial glycopeptide. Thromb. Res. 60, 9-18. https://doi.org/10.1016/0049-3848(90)90335-A
  3. Bergman, M., Varshavsky, L., Gottlieb, H. E. and Grosman, S. (2001) The antioxidant activity of aqueous spinach extract: chemical identifi cation of activity fractions. Phytochemistry 58, 143-152. https://doi.org/10.1016/S0031-9422(01)00137-6
  4. Cattaneo, M., Tenconi, P. M., Lecchi, A. and Mannucci, P. M. (1991) In vitro effects of picotamide on human platelet aggregation, the release reaction and thromboxane B2 production. Thromb. Res. 62, 717-724. https://doi.org/10.1016/0049-3848(91)90375-7
  5. Charo, I. F., Feinman, R. D. and Detwiler, T. C. (1997) Interrelations of platelet aggregation and secretion. J. Clin. Invest. 60, 866-873.
  6. Cho, H. J., Ham, H. S., Lee, T. K., Jung, Y. J., Choi, S. A., Kang, H. C. and Park, H. J. (2004) Inhibitory effect of cordycepin on human platelet aggregation. J. Biomed. Lab. Sci. 10, 1-8.
  7. Davie, E. W. and Ratnoff, O. D. (1964) Waterfall sequence for intrinsic blood clotting. Science 145, 1310-1312. https://doi.org/10.1126/science.145.3638.1310
  8. Dogne, J. M., de Leval, X., Hanson, J., Frederich, M., Lambermont, B., Ghuysen, A., Casini, A., Masereel, B., Ruan, K. H., Pirotte, B. and Kolh, P. (2004) New developments on thromboxane and prostacylcin modulators part I: thromboxane modulators. Curr. Med. Chem. 11, 1223-1241. https://doi.org/10.2174/0929867043365260
  9. Edwards, A. J., You, C. S., Swanson, J. E. and Parker, R. S. (2001) A novel extrinsic reference method for assessing the vitamin A of plant foods. Am. J. Clin. Nutr. 74, 348-355.
  10. Furie, B. and Furie, B. C. (1988) The molecular basis of blood coagulation. Cell 53, 505-518. https://doi.org/10.1016/0092-8674(88)90567-3
  11. Gorman, R. R., Johnson, R. A., Spilman, C. H. and Aiken, J. W. (1983) Inhibition of platelet thromboxane A2 synthase activity by sodium 5-(3'-pyridinylmethyl)benzofuran-2-carboxylate. Prostaglandins 26, 325-342. https://doi.org/10.1016/0090-6980(83)90099-0
  12. Hamberg, M., Svensson, J. and Samuelsson, B. (1975) Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. 72, 2994-2998. https://doi.org/10.1073/pnas.72.8.2994
  13. Hanson, J., Rolin, S., Reynaud, D., Qiao, N., Kelley, L. P., Reid, H. M., Valentin, F., Tippins, J., Kinsella, B. T., Masereel, B., Pace-Asciak, C., Pirotte, B. and Dogne, J. M. (2005) In vitro and in vivo pharmacological characterization of BM-613 [N-n-pentyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], a novel dual thromboxane synthase inhibitor and thromboxane receptor antagonist. J. Pharmacol. Exp. Ther. 313, 293-301.
  14. Jang, E. K., Azzam, J. E., Cickinson, N. T., Davidson, M. M. and Haslam, R. J. (2002) Roles for both cyclic GMP and cyclic AMP in the inhibition of collagen-induced platelet aggregation by nitroprusside. Br. J. Haematol. 117, 664-675. https://doi.org/10.1046/j.1365-2141.2002.03479.x
  15. Kimura, Y., Okuda, H. and Arichi, S. (1988) Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets. J. Pharm. Pharmacol. 40, 838-843. https://doi.org/10.1111/j.2042-7158.1988.tb06285.x
  16. Lomnitski, L., Bergman, M., Nyska, A., Ben-Shaul, V. and Grosman, S. (2003) Composition, effi cacy, and safety of spinash extracts. Nutr Cancer. 46, 222-231. https://doi.org/10.1207/S15327914NC4602_16
  17. Moncada, S. and Vane, J. R. (1978) Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane $A_2$ and prostacyclin. Pharmacol. Rev. 30, 293-331.
  18. Moon, M. K., Ahn, J. Y., Kim, S., Ryu, S. Y., Kim, Y. S. and Ha, T. Y. (2010) Ethanol extract and saponin of Platycodon grandifl orum ameliorate scopolamine-induced amnesia in mice. J. Med. Food. 13, 584-588. https://doi.org/10.1089/jmf.2009.1310
  19. Nishikawa, M., Tanaka, T. and Hidaka, H. (1980) $Ca^2+$-calmodulindependent phosphorylation and platelet secretion. Nature 287, 863-865. https://doi.org/10.1038/287863a0
  20. Podolak, I., Galany, A. and Sobolewska, D. (2010) Saponins as cytotoxic agents: a review. Phytochem. Rev. 9, 425-474. https://doi.org/10.1007/s11101-010-9183-z
  21. Prinz-Langenohl, R., Bronstrup, A., Thorand, B., Hages, M. and Pietrzik, K. (1999) Availability of food folate in humans. J. Nutr. 129, 913-916.
  22. Sani, H. A., Rahat, A., Ismail, M., Rosli, R. and Endrini, S. (2004) Potential anticancer effect of red spinach (Amaranthus gangeticus) extract. Asia Pac. J. Clin. Nutr. 13, 396-400.
  23. Sano, Y., Sato, K., Uchida, M. and Murata, M. (2003) Blood coagulation fibrinolysis of rats fed fi sh oil: reduced coagulation factors especially involved in intrinsic pathway and increased activity of plasminogen activator inhibitor. Biosic. Biotechnol. Biochem. 67, 2100-2105. https://doi.org/10.1271/bbb.67.2100
  24. Schwartz, S. M., Heinmark, R. L. and Majesky, M. W. (1990) Developmental mechanisms underlying pathology of arteries. Physiol. Rev. 70, 1177-1209.
  25. Schwarz, U. R., Walter, U. and Eigenthaler, M. (2001) Taming platelets with cyclic nucleotides. Biochem. Pharmaco. 62, 1153-1161. https://doi.org/10.1016/S0006-2952(01)00760-2
  26. Sinha, A. K., Rao, A. K., Willis, J. And Colman, R. W. (1983) Inhibition of thromboxane A2 synthesis in human platelets by coagulation factor Xa. Proc. Natl. Acad. Sci. USA. 80, 6086-6090. https://doi.org/10.1073/pnas.80.19.6086
  27. Stegmeier, K., Pill, J., Muller-Beckmann, B., Schmidt, F. H., Witte, E. C., Wolff, H. P. and Patscheke, H. (1984) The pharmacological profi le of the thromboxane A2 antagonists BM 13.177. A new antiplatelet and anti-thrombotic drug. Thromb. Res. 35, 379-395. https://doi.org/10.1016/0049-3848(84)90230-5
  28. Sudo, T., Ito, H. and Kimura, Y. (2003) Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the antiplatelet drug, cilostazol, in platelets. Platelets 14, 381-390. https://doi.org/10.1080/09537100310001598819
  29. Tsai, Y. C., Lin, C. L. and Chen, B. H. (2010) Preparative chromatography of flavonoids and saponins in Gynostemma pentaphyllum and their antiploliferation effect on hepatoma cell. Phytomedicine. 18, 2-10. https://doi.org/10.1016/j.phymed.2010.09.004

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