Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside-Re ameliorates ischemia and reperfusion injury in the heart: a hemodynamics approach

  • Lim, Kyu Hee (Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Lim, Dae-Jun (Department of Otolaryngology, Medical School, Konkuk University) ;
  • Kim, Jong-Hoon (Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University)
  • Received : 2012.11.13
  • Accepted : 2013.02.18
  • Published : 2013.07.15
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Abstract

Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (${\pm}dp/dt_{max}$). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-${\alpha}$ (TNF-${\alpha}$) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-${\alpha}$ level. Treatment of G-Re at 30 and $100{\mu}M$ doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-${\alpha}$ level. In this study, G-Re at $100{\mu}M$ dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than $30{\mu}M$. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.

Keywords

References

  1. Ostadal B. The past, the present and the future of experimental research on myocardial ischemia and protection. Pharmacol Rep 2009;61:3-12. https://doi.org/10.1016/S1734-1140(09)70002-7
  2. Gross GJ, Kersten JR, Warltier DC. Mechanisms of postischemic contractile dysfunction. Ann Thorac Surg 1999;68:1898-1904. https://doi.org/10.1016/S0003-4975(99)01035-8
  3. Piper HM, Garcia-Dorado D. Prime causes of rapid cardiomyocyte death during reperfusion. Ann Thorac Surg 1999;68:1913-1919. https://doi.org/10.1016/S0003-4975(99)01025-5
  4. Verma S, Fedak PW, Weisel RD, Butany J, Rao V, Maitland A, Li RK, Dhillon B, Yau TM. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation 2002;105:2332-2336. https://doi.org/10.1161/01.CIR.0000016602.96363.36
  5. Fleming PR. A short history of cardiology. Amsterdam: Rodopi Publishers, 1997.
  6. Rodriguez-Sinovas A, Abdallah Y, Piper HM, Garcia-Dorado D. Reperfusion injury as a therapeutic challenge in patients with acute myocardial infarction. Heart Fail Rev 2007;12:207-216. https://doi.org/10.1007/s10741-007-9039-9
  7. Buja LM. Myocardial ischemia and reperfusion injury. Cardiovasc Pathol 2005;14:170-175. https://doi.org/10.1016/j.carpath.2005.03.006
  8. Kim JH. Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012;36:16-26. https://doi.org/10.5142/jgr.2012.36.1.16
  9. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 2008;88:581-609. https://doi.org/10.1152/physrev.00024.2007
  10. Hardoon SL, Whincup PH, Lennon LT, Wannamethee SG, Capewell S, Morris RW. How much of the recent decline in the incidence of myocardial infarction in British men can be explained by changes in cardiovascular risk factors? Evidence from a prospective population-based study. Circulation 2008;117:598-604. https://doi.org/10.1161/CIRCULATIONAHA.107.705947
  11. Heidenreich PA, McClellan M. Trends in treatment and outcomes for acute myocardial infarction: 1975-1995. Am J Med 2001;110:165-174. https://doi.org/10.1016/S0002-9343(00)00712-9
  12. Luepker RV. Decline in incident coronary heart disease: why are the rates falling? Circulation 2008;117:592-593. https://doi.org/10.1161/CIRCULATIONAHA.107.747477
  13. Peng DC, Chen WP, Xie JT. Antihyperglycemic effects of ginseng and possible mechanisms. Drugs Future 2008;33:507-514. https://doi.org/10.1358/dof.2008.033.06.1188424
  14. Chevallier A. Encyclopedia of herbal medicine. New York: DK Publishing, 2000.
  15. Park YH, Kim YC, Park SU, Lim HS, Kim JB, Cho BK, Bae H. Age-dependent distribution of fungal endophytes in Panax ginseng roots cultivated in Korea. J Ginseng Res 2012;36:327-333. https://doi.org/10.5142/jgr.2012.36.3.327
  16. Blumenthal M, Goldberg A, Brinckmann J, Foster S, Tyler VE. Ginseng root. Newton: Integrative Medicine Communications, 2000.
  17. Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. Adv Data 2004;(343):1-19.
  18. Lee SJ, Sung JH, Lee SJ, Moon CK, Lee BH. Antitumor activity of a novel ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin. Cancer Lett 1999;144:39-43. https://doi.org/10.1016/S0304-3835(99)00188-3
  19. Baek SH, Bae ON, Park JH. Recent methodology in ginseng analysis. J Ginseng Res 2012;36:119-134. https://doi.org/10.5142/jgr.2012.36.2.119
  20. Shi Y, Sun C, Zheng B, Li Y, Wang Y. Simultaneous determination of nine ginsenosides in functional foods by high performance liquid chromatography with diode array detector detection. Food Chem 2010;123:1322-1327. https://doi.org/10.1016/j.foodchem.2010.06.014
  21. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1-8. https://doi.org/10.1016/S0006-2952(97)00193-7
  22. Kim DH. Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 2012;36:1-15. https://doi.org/10.5142/jgr.2012.36.1.1
  23. Xie JT, Mehendale SR, Li X, Quigg R, Wang X, Wang CZ, Wu JA, Aung HH, A Rue P, Bell GI et al. Anti-diabetic effect of ginsenoside Re in ob/ob mice. Biochim Biophys Acta 2005;1740:319-325. https://doi.org/10.1016/j.bbadis.2004.10.010
  24. Xie JT, Shao ZH, Vanden Hoek TL, Chang WT, Li J, Mehendale S, Wang CZ, Hsu CW, Becker LB, Yin JJ et al. Antioxidant effects of ginsenoside Re in cardiomyocytes. Eur J Pharmacol 2006;532:201-207. https://doi.org/10.1016/j.ejphar.2006.01.001
  25. Peng L, Sun S, Xie LH, Wicks SM, Xie JT. Ginsenoside Re: pharmacological effects on cardiovascular system. Cardiovasc Ther 2012;30:e183-e188. https://doi.org/10.1111/j.1755-5922.2011.00271.x
  26. Minematsu T, Ohtani H, Yamada Y, Sawada Y, Sato H, Iga T. Quantitative relationship between myocardial concentration of tacrolimus and QT prolongation in guinea pigs: pharmacokinetic/pharmacodynamic model incorporating a site of adverse effect. J Pharmacokinet Pharmacodyn 2001;28:533-554. https://doi.org/10.1023/A:1014460404352
  27. Ohtani H, Hanada E, Yamamoto K, Sawada Y, Iga T. Pharmacokinetic-pharmacodynamic analysis of the electrocardiographic effects of terfenadine and quinidine in rats. Biol Pharm Bull 1996;19:1189-1196. https://doi.org/10.1248/bpb.19.1189
  28. Song SB, Tung NH, Quang TH, Ngan NT, Kim KE, Kim YH. Inhibition of TNF-$\alpha$-mediated NF-$\kappa{B}$ transcriptional activity in HepG2 cells by dammarane-type saponins from Panax ginseng leaves. J Ginseng Res 2012;36:146-152. https://doi.org/10.5142/jgr.2012.36.2.146
  29. Yang Y, Hu SJ, Li L, Chen GP. Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in isolated rat hearts. Acta Pharmacol Sin 2009;30:54-60. https://doi.org/10.1038/aps.2008.12
  30. Peng Y, Sun Z. Characterization of QT and RR interval series during acute myocardial ischemia by means of recurrence quantification analysis. Med Biol Eng Comput 2011;49:25-31. https://doi.org/10.1007/s11517-010-0671-5
  31. Bak I, Lekli I, Juhasz B, Nagy N, Varga E, Varadi J, Gesztelyi R, Szabo G, Szendrei L, Bacskay I et al. Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts. Am J Physiol Heart Circ Physiol 2006;291:H1329-H1336. https://doi.org/10.1152/ajpheart.01243.2005
  32. Hearse DJ, Sutherland FJ. Experimental models for the study of cardiovascular function and disease. Pharmacol Res 2000;41:597-603. https://doi.org/10.1006/phrs.1999.0651
  33. Patel V, Upaganlawar A, Zalawadia R, Balaraman R. Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: a biochemical, electrocardiographic and histoarchitectural evaluation. Eur J Pharmacol 2010;644:160-168. https://doi.org/10.1016/j.ejphar.2010.06.065
  34. Ramani R, Mathier M, Wang P, Gibson G, Togel S, Dawson J, Bauer A, Alber S, Watkins SC, McTiernan CF et al. Inhibition of tumor necrosis factor receptor-1-mediated pathways has beneficial effects in a murine model of postischemic remodeling. Am J Physiol Heart Circ Physiol 2004;287:H1369-H1377. https://doi.org/10.1152/ajpheart.00641.2003

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