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http://dx.doi.org/10.5142/JGR.2007.31.1.023

Cardioprotective Effect of the Mixture of Ginsenoside Rg3 and CK on Contractile Dysfunction of Ischemic Heart  

Kim, Jong-Hoon (Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University)
Publication Information
Journal of Ginseng Research / v.31, no.1, 2007 , pp. 23-33 More about this Journal
Abstract
Ginsenosides are one of the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in korea. The anti-ischemic effects of the mixture of ginsenoside $Rg_3$, and CK on ischemia-induced isolated rat heart were investigated through analyses of changes in hemodynamics ; blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into four groups: normal control, the mixture of ginsenoside $Rg_3$ and CK, an ischemia-induced group without any treatment, and an ischemia-induced group treated with the mixture of ginsenoside $Rg_3$ and CK. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between them before ischemia was induced. The supply of oxygen and buffer was stopped for five minutes to induce ischemia in isolated rat hearts, and the mixture of ginsenoside $Rg_3$ and CK was administered during ischemia induction. Treatments of the mixture of ginsenoside $Rg_3$ and CK significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, hemodynamics (except heart rate) of the group treated with the mixture of ginsenoside $Rg_3$ and CK significantly recovered 60 minutes after reperfusion compared to the control group (mixture+ischemia vs ischemia - average perfusion pressure: 74.4${\pm}$2.97% vs. 85.1${\pm}$3.01%, average aortic flow volume: 49.11${\pm}$2.72% vs. 59.97${\pm}$2.93%, average coronary flow volume: 58.50${\pm}$2.81% vs. 72.72${\pm}$2.99%, and average cardiac output: 52.47${\pm}$2.78% vs. 63.11${\pm}$2.76%, p<0.01, respectively). These results suggest that treatment of the mixture of ginsenoside $Rg_3$ and CK has distinct anti-ischemic effects in ex vivo model of ischemia-induced rat heart.
Keywords
Ginsenoside Rg$_{3}$; Compound K; Langendorff apparatus; working heart; I/R injury; Hemodynamics; Cardiac output;
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1 Kim, H.S., Lee, J.H., Koo, Y.S. and Nah, S.Y.: Effects of ginsenosides on $Ca^{2+}$ channels and membrane capacitance in rat adrenal chromaffin cells. Br. Res. Bull. 46, 245-251 (1998a)   DOI   ScienceOn
2 Nah, S.Y. and McCleskey, E.W.: Ginseng root extract inhibits calcium channels in rat sensory neurons through a similar path, but different receptor, as type opioids. J. Ethnopharmacol. 42, 45-51 (1994)   DOI   ScienceOn
3 Chu, G.X. and Chen, X.: Anti-lipid peroxidation and protection of ginsenosides against cerebral ischemia-reperfusion injury of rats. Acta Pharma. Sin. 11, 119-123 (1990)
4 Chu, G.X. and Chen, X.: Protective effect of ginsenosides on acute cerebral ischemia-reperfusion injury of rats. Cha. J. Pharmacol. and Toxicol. 3, 18-23 (1989)
5 Yu, X.C., Wu, S., Wang, G.Y., Shan, J., Wong, T.M., Chen, C.F. and Pang, K.T.: Cardiac effects of the extract and active components of radix stephaniae tetrandrae. II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart. Life Sci. 68, 2863-2872 (2001)   DOI   ScienceOn
6 Jeon, B.H., Kim, C.S., Park, K.S., Lee, J.W., Park, H.B., Kim, K.J., Kim, S.H., Chang, S.J. and Nam, K.Y. : Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. Gen. Pharmacol. 35, 135-141 (2000)   DOI   ScienceOn
7 Bourdillon, P.D. and Poole-Wilson, P.A.: Effects of ischaemia and reperfusion on calcium exchange and mechanical function in isolated rabbit myocardium. Cardiovasc. Res. 15, 121-130 (1981)   DOI
8 Kim, N.D., Kang, S.Y., Kim, M.J., Park, J.H. and Schini-Kerth, V.B.: The ginsenoside $Rg_3$ evokes endothelium-independent relaxation in rat aorti rings:role of $K^+$ channels. Eur. J. Pharmacol. 367, 51-57 (1999a)   DOI   ScienceOn
9 Galagudza, M., Kurapeev, D., Minasian, S., Valen, G. and Vaage, J.: Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm. Eur. J. Cardiothorac Surg. 25, 1006-1010 (2004)   DOI   ScienceOn
10 Han, K.H., Choe, S.C., Kim, H.S., Sohn, D.W., Nam, K.Y., Oh, B.H., Lee, M.M., Park, Y.B., Choi, Y.S., Seo, J.D. and Lee, Y.W.: Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. Am. Chin. Med., 26, 199-209 (1998)   DOI   ScienceOn
11 Sung, J., Han, K.H., Zo, J.H., Park, H.J., Kim, C.H. and Oh, B.H.: Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am. J. Chin. Med. 28, 205-216 (2000)   DOI   ScienceOn
12 Toda, N., Ayajiki, K., Fujioka, H. and Okamura, T.: Ginsenoside potentiates NO-mediated neurogenic vasodilatation of monkey cerebral arteries. J. Ethnopharmacol. 76, 109-113 (2001)   DOI   ScienceOn
13 Shibata, S., Tanaka, O., Ando, T., Sado, M., Tsushima, S. and Ohsawa, T.: Chemial studies on oriental plant drugs. XIV. Protopanaxadiol,a genuine sapogenin of ginseng saponins. Chem. Pharm. Bull., 14, 595-600 (1966)   DOI   ScienceOn
14 Lee, J.H., Jeong, S.M., Kim, J.H., Lee, B.H., Yoon, I.S., Lee, J.H., Choi, S.H., Lee, S.M., Park, Y.S., Lee, J.H., Kim, S.S., Kim, H.C., Lee, B.Y. and Nah, S.Y.: Effects of Ginsenosides and Their Metabolites on Voltage dependent $Ca^{2+}$ Channel Subtypes. Mol. Cells. 21(1), 52-62 (2006)
15 Sohn, E.S., Huh, B.Y., Park, S.C., Park, C.W. and Kim, H.J. : The effect of ginseng on blood pressure in spontaneous hypertensive rat and essential hypertension. Proceedings of the 3rd International Ginseng Symposium. Korean Gin. Res.. Institute, Seoul, Korea. 1-3 (1980)
16 Kim, N.D., Kang, S.Y. and Schini, V.B.: Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta. Gen. Pharmacol. 25, 1071-1077 (1994)   DOI   ScienceOn
17 Liao, P., Wang, S.Q., Wang, S., Zheng, M., Zheng, M., Zhang, S.J., Cheng, H., Wang, Y. and Xiao, R.P.: p38 mitogen-activated protein kinase mediates a negative inotropic effect in cardiac myocytes. Circ. Res. 90, 190-196 (2002)   DOI
18 Maulik, N., Yoshida, T. and Das, D.K. : Oxidative stress developed during the reperfusion of ischemic myocardium induces apoptosis. Free Radiac. Biol. Med. 24, 869-875 (1998)   DOI   ScienceOn
19 Sun, J., Tan, B.K., Huang, S.H., Whiteman, M. and Xhu, Y.Z.: Effects of natural products on ischemic heart diseases and cardiovascular system. Acta. Pharmacol. Sin. 23, 1142-1151 (2002)
20 Wang, Y.G., Benedict, W.J., Huser, J., Samarel, A.M., Blatter, L.A. and Lipsius, S.L.: Brief rapid pacing depresses contractile function via Ca(2+)/PKC-dependent signaling in cat ventricular myocytes. Am. J. Physiol, Heart Circ. Physiol. 280, H90-H98 (2001)
21 Kaneko, M., Beamish, R.E. and Dhalla, N.S. : Depression of heart sarcolemmal $Ca^{2+}$ -pump activity by oxygen free radicals. Am. J. Physiol. 256, H368-H374 (1989a)
22 Kim, N.D., Kang, S.Y., Park, J.H. and Schini-Kerth, V.B. : Ginsenoside $Rg_3$ mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of $K^+$ channels. Eur. J. Pharmacol. 367, 41-49 (1999b)   DOI   ScienceOn
23 Shen, A.C. and Jennings, R.B.: Kinetics of calcium accumulation in acute myocardial ischemic injury. Am. J. Pathol. 67, 441-452 (1972)
24 Shen, A.C. and Jennings, R.B.: Myocardial calcium and magnesium in acute ischemic injury. Am. J. Pathol. 67, 417-440 (1972)
25 An, J., Varadarajan, S.G. and Camara, A. : Blocking $Na^+/H^+$ exchange reduces $[Na^+]_i\;and\;[Ca^{2+}]_i$ load after ischemia and improves function in intact hearts. Am. J. Physiol. 281, H2396-H2409 (2001)
26 Toda, N., Ayajiki, K., Fujioka, H. and Okamura, T.: Ginsenoside potentiates NO-mediated neurogenic vasodilatation of monkey cerebral arteries. J Ethnopharmacol. 76(1), 109-113 (2001)   DOI   ScienceOn
27 Sun, H.Y., Wang, N.P. and Halkos, M.E. : Involvement of $Na^+/H^+$ exchanger in hypoxia/re-oxygenation-induced neonatal rat cardiomyocyte apoptosis. Eur. J. Pharmacol. 486, 121-131 (2004)   DOI   ScienceOn
28 Micheal, P.H., Meuter, K. and Schasfer, C.: Cellular mechanisms of ischemia-reperfusion injury. Ann. Thorac. Surg. 75, S644-S648 (2003)   DOI   ScienceOn
29 Kim, N.D., Kang, S.Y. and Schini, V.B. : Ginsenosides evoke endothelium-dependent vascular relaxation in rat aorta. Gen Pharmacol. 25(6), 1071-1077 (1994)   DOI   ScienceOn
30 Jiang, Y., Zhong, G., Shao, C. and Yue, G.: $Ca^{2+}$ channel blocking effect of panaxadiol saponins and panaxatriol saponins of cultured cardiac cells. Zhongguo Zhong Yao Za Zhi. 192 Mar 17(3), 172-173 (1992)
31 Li, X.S., Urriuda, Y., Wang, Q.D., Norlander, R., Sjoouist, P.O. and Pernow, J.: Role of L-arginine in preventing myocardial and endothelial injury following ischaemia/ reperfusion in the rat isolated heart. Acta. Physiol. Scand. 156, 37-44 (1996)   DOI   ScienceOn
32 Asano, G., Takashi, E., Ishiwata, T., Onda, M., Yokoyama, M., Naito, Z., Ashraf, M. and Sugisaki, Y. : Pathogenesis and protection of ischemia and reperfusion injury in myocardium. J. Nippon Med. Sch. 70, 384-392 (2003)   DOI
33 Ferrari, R., Alfieri, O., Curello, S., Ceconi, C., Cargnoni, A., Marzollo, P., Pardini, A., Caradonna, E. and Visioli, O.: Occurrence of oxidative stress during reperfusion of the human heart. Circulation. 81, 201-211 (1990)   DOI   ScienceOn
34 Rhim, H., Kim, H., Lee, D.Y., Oh, T.H. and Nah, S.Y.: Ginseng and ginsenoside $Rg_3$, a newly identified active ingredient of ginseng, modulate $Ca^{2+}$ channel currents in rat sensory neurons. Eur. J. Pharmacol. 436, 151-158 (2002)   DOI   ScienceOn
35 Temsah, R.M., Netticadan, T., Chapman, D., Takeda, S., Mochizuki, S. and Dhalla, N.S.: Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart. Am. J. Physiol. 277, H584-H594 (1999)
36 Bolli, R. and Marban, E.: Molecular and cellular mechanisms of myocardial stunning. Physiol. Rev. 29, 610-636 (1999)
37 Sharikabad, M.N., Hagelin, E.M., Hagberg, I.A., Lyberg, T. and Brors, O.: Effect of calcium on reactive oxygen species in isolated rat cardiomyocytes during hypoxia and reoxygenation. J. Mol. Cell. Cardiol. 32, 441-452 (2000)   DOI   ScienceOn
38 Kaneko, M., Elimban, V. and Dhalla, N.S.: Mechanism for depression of heart sarcolemmal $Ca^{2+}$ pump by oxygen free radicals. Am. J. Physiol. 257, H804-H811 (1989b)
39 Zhong, G. and Jiang, Y.: Calcium channel blockage and anti-free-radical actions of ginsenosides. Chin Med J (Engl). 110(1), 28-29 (1997)
40 Nah, S.Y., Park, H.J. and McCleskey, E.W.: A trace component of ginseng that inhibits $Ca^{2+}$ channels through a pertussis toxin-sensitive G protein. Proc. Natl Acad. Sci. 92, 8739-8743 (1995)