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

다국어 초록 (Multilingual Abstract)

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and Ca<SUP>2+</SUP>-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase Cβ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate (PIP₂) 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 PIP₂, 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, PT inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free Ca<SUP>2+</SUP>[Ca<SUP>2+</SUP>]i) up to 72% as compared with control (30.8±0.9 nM) in intact platelet. However, PT (100 ㎍/ml) inhibited the thrombin-elevated [Ca<SUP>2+</SUP>]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<SUP>2+</SUP>]i level and PIS breakdown.

목차 (Table of Contents)

• Abstracts
• INTRODUCTION
• MATERIALS AND METHODS
• RESULTS AND DISCUSSION
• ACKNOWLEDGEMENT
• REFERENCES

참고문헌 (Reference)

1 田村泰, "高麗人蔘の抗血小板作用の解析,藥用人蔘" 共立出版株式會社 109-121, 1989

2 Agranoff, B. W., "Thrombininduced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets" 258 : 2076-2078, 1983

3 Nishizuka, Y., "The role of protein kinase C in cell surface signal transduction and tumor promotion" 308 : 693-697, 1984

4 Shibata, S., "Studies on saponins and sapogenins of ginseng.The structure of panaxatriol" 42 : 207-213, 1965

5 Majerus, P. W., "Production of phosphoinositide-derived messenger" 37 : 701-703, 1984

6 Kito, M., "Phosphoinositide breakdown as an indirect link between stimulation and aggregation of rat platelets by thrombin and collagen" 97 : 765-772, 1985

7 Park, H. J., "Panaxadiol from Panax ginseng C. A, Meyer inhibits synthesis of thromboxane A2 in platelet aggregation induced by thrombin" 17 : 131-124, 1993

8 Park, K. M., "Panaxadiol and panaxatriol from Panax ginseng C. A. Meyer inhibit the synthesis of thromboxane A2 in adrenaline-stimulated human platelet aggregation" 18 : 44-48, 1994

9 Savage, B., "Mechanisms of platelet aggregation" 8 : 270-26, 2001

10 Narita, H., "Insufficient mobilization of calcium by early breakdown of phosphatidylinositol 4,5-bisphosphate for aggregation ofhuman platelets by collagen" 98 : 1063-1068, 1985

11 Berridge, M. J., "Inositol trisphosphate, a novel second messenger in cellular signal transduction" 312 : 315-321, 1984

12 Furuichi, T., "Inositol 1,4,5-trisphosphate receptor-mediated Ca2+-signaling in the brain" 64 : 953-960, 1995

13 Cattaneo, M., "In vitro effects of picotamide on human platelet aggregation,the release reaction and thromboxane B2 production" 62 : 717-724, 1991

14 Kimura, Y., "Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets" 40 : 838-843, 1988

15 Park, H. J., "Effects of protein fraction and ginsenosides from Panax ginseng C. A. Meyer on substrate phosphorylation by a catalytic fragment of protein kinase C" 27 : 280-283, 1994

16 Rim, K. T., "Effects of ginsenosides from red ginseng on the enzymes of cellular signal transduction system" 21 : 19-27, 1997

17 Park, H. J., "Effects of dietary supplementation of lipophilic fraction from Panax ginseng on cGMP and cAMP in rat platelets and on blood coagulation" 19 : 1434-1439, 1996

18 Park, H. J., "Effect of non-saponin fraction from Panax ginseng on cGMP and thromboxane A2 in human platelet aggregation" 49 : 157-162, 1995

19 Lee, J. H, "Effect of lipophilic fraction from Panax ginseng on phosphatidylinositol breakdown in rat platelets activated by collagen" 7 : 47-51, 1997

20 Takamura, H., "Differential hydrolysis of phospholipid molecular species during activation of human platelets with thrombin and collagen" 262 : 2262-2269, 1987

21 Schwartz, S. M., "Developmental mechanisms underlying pathology of arteries" 70 : 1177-1209, 1990

22 Tanaka, O., "Chemical studies on the oriental plant drugs. XVI. The stereochemistry of protopanaxadiol,a genuine sapogenin of ginseng" 14 : 1150-1156, 1966

23 Tsien, R. Y., "Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new intracellulary trapped fluorescent indicator" 94 : 325-334, 1982

24 Nishikawa, M., "Ca2+-calmodulindependent phosphorylation and platelet secretion" 287 : 863-865, 1980

25 Kuo, S. C., "Antiplatelet components in Panax ginseng" 56 : 164-167, 1990