Anti-platelet Aggregation Study of Fermented Galgeun Tang and Fermented Ssanghwa Tang

발효 갈근탕과 쌍화탕의 혈소판 응집 억제 효과 연구

  • 손추영 (충남대학교 약학대학 임상약학실) ;
  • 송병정 (충남대학교 약학대학 임상약학실) ;
  • 마진열 (한국 한의학 연구원) ;
  • 권광일 (충남대학교 약학대학 임상약학실)
  • Received : 2011.06.07
  • Accepted : 2011.08.23
  • Published : 2011.10.31

Abstract

This study was performed to evaluate enhanced effect of fermented Galgeun tang (GGT) and Ssanghwa tang (SHT) on the anti-platelet aggregation. Platelet aggregation assay was performed In vitro using human platelet rich plasma(PRP) and In vivo using SD-rat plasma by platelet aggregometer. Pharmacodynamic parameters, $E_{max}$ and $EC_{50}$, were calculated using Winnolin. SD-rats administered 1 g/kg of oriental medicine every 12 hr for 8 days. Platelet aggregation was measured by optical method with collagen inducer (4 ${\mu}g$/ml). In In vitro anti-platelet study, $EC_{50}$ of GGT-A was lower than that of GGT-con about 79.13 ${\mu}g$/ml. And $EC_{50}$ of SHT-A and SHT-B was lower than that of SHT-con about 122.73 and 110.15 ${\mu}g$/ml, respectively. It is assumed that fermented GGT and SHT were more effective than original medicine. In multiple administration study, anti-platelet effect was significantly increased both GGT and SHT. Fermented GGT and SHT were more effective than original herbal medicine on anti-platelet aggregation.

Keywords

References

  1. Jin, J. S., Nishihata, T., Kakiuchi, N. and Hattori, M. : Biotransformation of C-Glucosylisoflavone puerarin to estrogenic (3S)-equol in co-culture of two human intestinal bacteria. Biol. Pharm. Bull. 31, 1621 (2008). https://doi.org/10.1248/bpb.31.1621
  2. Kenneth, D. R. S., Nadine, M. B. and Eva, L. O. : The clinical importance of the metabolite equol a clue to the effectiveness of soy and its isoflavones. J. Nutr. 132, 3577 (2002). https://doi.org/10.1093/jn/132.12.3577
  3. 박영순 : 한방의 약리해설, 아카데미서적, 서울 p. 196 (2002).
  4. Kim, D. S., Um, Y. R., Yang, M. C., Yun, N. Y. and Ma, J. Y. : Polyphenol contents and antioxidant activities of fractions from Ssanghwa-tang and fermented Ssanghwa-tang. Korean Journal of Oriental Medicine. 18, 175 (2010).
  5. Yun, Y. P., Do, J. H., Ko, S. R., Ryu, S. Y., Kim, J. H., Song, H. C., Park, Y. D., Ahn, K. S. and Kim, S. H. : Effect of Korean red ginseng and its mixed prescription on the high molecular weight dextran-induced blood stasis in rats and human platelet aggregation. Journal of Ethnopharmacology 77, 259 (2001). https://doi.org/10.1016/S0378-8741(01)00303-8
  6. Lee, Y. Y., Lee, S., Jin, J. L. and Yun-Choi, H. S. : Platelet antiaggreagatory effects of coumarins from the roots of Angelica genuflexa and A. gigas. Arch. Pharm. Res. 26, 723 (2003). https://doi.org/10.1007/BF02976681
  7. Sugidachi, A., Ogawa, T., Kurihara, A., Hagihara, K. and Jakubowski, J. A. : The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel's active metabolite. Journal of Thrombosis and Haemostasis 5, 1545 (2007). https://doi.org/10.1111/j.1538-7836.2007.02598.x
  8. 이귀희, 임현정, 신선미, 유동열 : 청열조혈탕가미방의 항혈전작용 에 대한 실험적 연구. 대한한방부인과학회지 22, 79 (2009).
  9. 장정순, 이철규, 신장식, 조일환, 서정진 : 구인 (Lumbricus rubellus) 추출물의 혈전 분해 및 항혈전 효과. 약학회지 39, 666 (1995).
  10. Schumacher, W. A., Bostwick, J. S., Ogletree, M. L., Stewart, A. B., Steinbacher, M. A., Hua, J., Price, L. A., Wong, P. C. and Rehfuss, R. P. : Biomarker optimization to track the antithrombotic and hemostatic effects of clopidogrel in rats. The Journal of Pharmacology and Experimental Therapeutics. 322, 369 (2007). https://doi.org/10.1124/jpet.106.119156
  11. 김의일, 신용완, 김수민, 이정은, 유동열 : 행경홍화탕의 항혈전 작용에 대한 실험적 연구. 대한한방부인과학회지 19, 1 (2006)
  12. 류동훈, 신용완, 김의일, 김수민, 이정은, 유동열 : 홍화당귀산의 항혈전 작용에 대한 실험적 연구. 대한한방부인과학회지 19, 31 (2006).
  13. Kim, D. H., Hong, S. W., Kim, B. T., Bae, E. A., Park, H. Y. and Han, M. J. : Biotransformation of Glycyrrhizin by human intestinal bacteria and its relation to biological activities. Arch. Pharm. Res. 23, 172 (2000). https://doi.org/10.1007/BF02975509
  14. Pyo, M. K., Koo, Y. K. and YunChoi, H. S. : Anti-platelet effect of the phenolic constituents isolated from the leasves of magnolia obovata. Natural Product Sciences 8, 147 (2002).
  15. Zhu, M., Tang, Y., Duan, J., Guo, J., Guo, S., Su, S., Shang, E., Qian, D. and Ding, A. : Roles of paeoniflorin and senkyunolide I in SiWu decoction on antiplatelet and anticoagulation activities. J. Sep. Sci. 33, 3335 (2010). https://doi.org/10.1002/jssc.201000340
  16. Guh, J. H., Ko, F. N., Jong, T. T. and Teng, C. M. : Antiplatelet effect of gingerol isolated from zingiber officinale. Journal of Pharmacy and Pharmacology 47, 329 (1995). https://doi.org/10.1111/j.2042-7158.1995.tb05804.x
  17. Choo, M. K., Park, E. K., Yoon, H. K. and Kim, D. H. : Antithrombotic and antiallergic of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora. Biological & Pharmaceutical Bulletin. 25 (2002).
  18. Toru, I., Mariusz, K. P., Sachiko, O., Akio, O., Koichiro, T., Makoto, S., Shigehiro, K., Yoshiro, K. and Mamoru, K. : Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. Journal of Nutrition. 130, 1695 (2000). https://doi.org/10.1093/jn/130.7.1695
  19. Kaeko, M. and Junji, T. : Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Archives of Biochemistry and Biophysics 417, 12 (2003). https://doi.org/10.1016/S0003-9861(03)00284-4
  20. Eriko, K., Norifumi, S., Yuji, O., Ken, K., Osamu, I., Kunio, K., Akiharu, F. and Michio, U. : Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans. Food and Chemical Toxicology 41, 875 (2003). https://doi.org/10.1016/S0278-6915(03)00039-5
  21. Yan, L. and Ming, H. : Absorption and metabolism of flavonoids in the Caco-2 cell culture model and a perused rat intestinal model. Drug Metabolism and Disposition 30, 370 (2011).
  22. 이창호, 김병수, 신미경, 우청주, 김정희, 권기영, 박희동 : 상황 버섯 추출액을 이용하여 제조한 된장의 효소 활성 및 기능성의 변화. Korean J. Food. Preserv. 15, 736 (2008).
  23. Francischetti, I. M., Monteiro, R. Q. and Guimaraes, J. A. : Identification of glycyrrhizin as a thrombin inhibition. Biochem. Biophys. Res. Commun. 235, 259 (1997). https://doi.org/10.1006/bbrc.1997.6735
  24. Okuyama, T., Shibata, S., Hoson, M., Kawada, T., Osada, H. and Noguchi, T. : Effect of oriental plant drugs on platelet aggregation; III. Effect of chines drug "Xiebai" on human platelet aggregation. Planta. Med. 52, 171 (1986). https://doi.org/10.1055/s-2007-969113
  25. Koo, Y. K., Kim, J. M., Koo, J. Y., Kang, S. S., Bae, K., Kim, Y. S., Chung, J. H. and Yun-Choi, H. S. : Platelet antiaggregator and blood anti-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa. Pharmazie. 65, 624 (2010).