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Inhibitory Effects of Panaxatriol from Panax ginseng C. A. Meyer on Phosphoinositide Breakdown Induced by Thrombin in Platelets

  • Park, Kyeong-Mee (College of Oriental Medicine, Daejon University) ;
  • Rhee, Man-Hee (Department of Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Shin, Han-Jae (KT&G Central Research Institute) ;
  • Song, Yong-Bum (KT&G Central Research Institute) ;
  • Hyun, Hak-Chul (KT&G Central Research Institute) ;
  • Park, Ki-Hyun (Korea Institute of Science and Technology Information) ;
  • Cho, Hyun-Jeong (Dream Pharma) ;
  • Choi, Sun-A (Postgraduate School of Medical Science, Busan National University) ;
  • Kang, Hyo-Chan (Department of Medicine Laboratory Science, College of Dong-Eui Institute of Technology) ;
  • Kim, Kyoung-Jin (Department of Food & Drug research, Ulsan Institute of Health & Environment) ;
  • Kim, Hyeong-Soo (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Kang, Hee-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Ok, Woo-Jeong (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Lee, Dong-Ha (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University)
  • Published : 2008.06.30

Abstract

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and $Ca^{2+}$-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase $C_{\beta}$ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate $(PIP_2)$ was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of $PIP_2$, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, Pr inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free $Ca^{2+}([Ca^{2+}])_i$) up to 72% as compared with control $(30.8{\pm}0.9 nM)$ in intact platelet. However, PT (100 ${\mu}g/ml$) inhibited the thrombin-elevated $[Ca^{2+}]_i$ to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the $[Ca^{2+}]_i$ level and PIS breakdown.

Keywords

References

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