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Cardioprotective potential of Korean Red Ginseng extract on isoproterenol-induced cardiac injury in rats

  • Lim, Kyu Hee (Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University) ;
  • Ko, Dukhwan (Department of Orthopaedic Surgery, Medical School, Konkuk University) ;
  • Kim, Jong-Hoon (Department of Veterinary Physiology, College of Veterinary Medicine, Biosafety Research Institute, Chonbuk National University)
  • Received : 2012.10.30
  • Accepted : 2013.01.14
  • Published : 2013.07.15

Abstract

The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure ($+dP/dt_{max}$) and minimal rate of developed left ventricular pressure ($-dP/dt_{max}$), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

Keywords

References

  1. Kumar JS, Menon VP. Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction. Indian J Exp Biol 1992;30:122-127.
  2. Aronow WS. Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure. Cardiol Rev 2006;14:108-124. https://doi.org/10.1097/01.crd.0000175289.87583.e5
  3. Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med 1998;4:1241-1243. https://doi.org/10.1038/3218
  4. Cai Q, Rahn RO, Zhang R. Dietary flavonoids, quercetin, luteolin and genistein, reduce oxidative DNA damage and lipid peroxidation and quench free radicals. Cancer Lett 1997;119:99-107. https://doi.org/10.1016/S0304-3835(97)00261-9
  5. Dikshit M, Van Oosten MH, de Graff S, Srimal RC. Free radical scavenger mechanisms in experimentally induced ischemia in the rabbit heart and protective effect of verapamil. Arch Int Pharmacodyn Ther 1992;318:55-65.
  6. Nakamura T, Nishi H, Kokusenya Y, Hirota K, Miura Y. Mechanism of antioxidative activity of fluvastatin-determination of the active position. Chem Pharm Bull (Tokyo) 2000;48:235-237. https://doi.org/10.1248/cpb.48.235
  7. Rathore N, John S, Kale M, Bhatnagar D. Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat tissues. Pharmacol Res 1998;38:297-303. https://doi.org/10.1006/phrs.1998.0365
  8. Srivastava S, Chandrasekar B, Gu Y, Luo J, Hamid T, Hill BG, Prabhu SD. Downregulation of CuZn-superoxide dismutase contributes to beta-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res 2007;74:445-455. https://doi.org/10.1016/j.cardiores.2007.02.016
  9. Liu Z, Li Y, Li X, Ruan CC, Wang LJ, Sun GZ. The effects of dynamic changes of malonyl ginsenosides on evaluation and quality control of Panax ginseng C.A. Meyer. J Pharm Biomed Anal 2012;64-65:56-63. https://doi.org/10.1016/j.jpba.2012.02.005
  10. Yamabe N, Song KI, Lee W, Han IH, Lee JH, Ham J, Kim SN, Park JH, Kang KS. Chemical and free radical-scavenging activity changes of ginsenoside Re by maillard reaction and its possible use as a renoprotective agent. J Ginseng Res 2012;36:256-262. https://doi.org/10.5142/jgr.2012.36.2.256
  11. Ribeiro DA, Buttros JB, Oshima CT, Bergamaschi CT, Campos RR. Ascorbic acid prevents acute myocardial infarction induced by isoproterenol in rats: role of inducible nitric oxide synthase production. J Mol Histol 2009;40:99-105. https://doi.org/10.1007/s10735-009-9218-1
  12. Ramesh CV, Malarvannan P, Jayakumar R, Jayasundar S, Puvanakrishnan R. Effect of a novel tetrapeptide derivative in a model of isoproterenol induced myocardial necrosis. Mol Cell Biochem 1998;187:173-182. https://doi.org/10.1023/A:1006835526608
  13. Lum G, Gambino SR. A comparison of serum versus heparinized plasma for routine chemistry tests. Am J Clin Pathol 1974;61:108-113. https://doi.org/10.1093/ajcp/61.1.108
  14. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63. https://doi.org/10.1093/ajcp/28.1.56
  15. Rosalki SB. An improved procedure for serum creatine phosphokinase determination. J Lab Clin Med 1967;69:696-705.
  16. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for super-oxide dismutase. J Biol Chem 1972;247:3170-3175.
  17. Aebi H. Catalase in vitro. Methods Enzymol 1984;105: 121-126. https://doi.org/10.1016/S0076-6879(84)05016-3
  18. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179:588-590. https://doi.org/10.1126/science.179.4073.588
  19. Zhou R, Xu Q, Zheng P, Yan L, Zheng J, Dai G. Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol 2008;586:244-250. https://doi.org/10.1016/j.ejphar.2008.02.057
  20. Yuan HD, Quan HY, Jung MS, Kim SJ, Huang B, Kim DY, Chung SH. Anti-diabetic effect of pectinase-processed ginseng radix (GINST) in high fat diet-fed ICR mice. J Ginseng Res 2011;35:308-314. https://doi.org/10.5142/jgr.2011.35.3.308
  21. 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
  22. Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods 1985;14:157-167. https://doi.org/10.1016/0160-5402(85)90029-4
  23. Cho ES, Ryu SY, Jung JY, Park BK, Son HY. Effects of red ginseng extract on zearalenone induced spermatogenesis impairment in rat. J Ginseng Res 2011;35:294-300. https://doi.org/10.5142/jgr.2011.35.3.294
  24. Karthick M, Stanely Mainzen Prince P. Preventive effect of rutin, a bioflavonoid, on lipid peroxides and antioxidants in isoproterenol-induced myocardial infarction in rats. J Pharm Pharmacol 2006;58:701-707. https://doi.org/10.1211/jpp.58.5.0016
  25. Upaganlawar A, Gandhi C, Balaraman R. Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats. Plant Foods Hum Nutr 2009;64:75-80. https://doi.org/10.1007/s11130-008-0105-9
  26. Laine GA, Allen SJ. Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circ Res 1991;68:1713-1721. https://doi.org/10.1161/01.RES.68.6.1713
  27. Holland RP, Brooks H. TQ-ST segment mapping: critical review and analysis of current concepts. Am J Cardiol 1977;40:110-129. https://doi.org/10.1016/0002-9149(77)90109-6
  28. Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, Saxena A, Arya DS. Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Mol Cell Biochem 2004;260:39-47. https://doi.org/10.1023/B:MCBI.0000026051.16803.03
  29. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS. Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol 2002;34:379-388. https://doi.org/10.1006/jmcc.2002.1526
  30. Kim YS, Kim YH, Noh JR, Cho ES, Park JH, Son HY. Protective effect of Korean red ginseng against aflatoxin B1-induced hepatotoxicity in rat. J Ginseng Res 2011;35:243-349. https://doi.org/10.5142/jgr.2011.35.2.243
  31. Karthikeyan K, Bai BR, Devaraj SN. Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats. Int J Cardiol 2007;115:326-333. https://doi.org/10.1016/j.ijcard.2006.03.016
  32. Zhou B, Wu LJ, Li LH, Tashiro S, Onodera S, Uchiumi F, Ikejima T. Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1. J Pharmacol Sci 2006;102:387-395. https://doi.org/10.1254/jphs.FPJ06005X
  33. 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
  34. 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
  35. 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
  36. Deng HL, Zhang JT. Anti-lipid peroxilative effect of ginsenoside Rb1 and Rg1. Chin Med J (Engl) 1991;104:395-398.
  37. Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, Peng H, Aburaya J, Ishihara K, Sakanaka M. Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root. Neurosci Res 1997;28:191-200. https://doi.org/10.1016/S0168-0102(97)00041-2
  38. Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W, Wang C, Liu K. Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett 2005;374:92-97. https://doi.org/10.1016/j.neulet.2004.10.030
  39. Lu JM, Yao Q, Chen C. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 2009;7:293-302. https://doi.org/10.2174/157016109788340767
  40. Saw CL, Yang AY, Cheng DC, Boyanapalli SS, Su ZY, Khor TO, Gao S, Wang J, Jiang ZH, Kong AN. Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol 2012;25:1574-1580. https://doi.org/10.1021/tx2005025

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