Journal of Ginseng Research

  • 제33권4호
  • /
  • Pages.283-293
  • /
  • 2009
  • /
  • 1226-8453(pISSN)
  • /
  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
권호 표지
DOI QR코드

DOI QR Code

Protective Roles of Ginseng Saponin in Cardiac Ischemia and Reperfusion Injury

  • Kim, Jong-Hoon (Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Biosafety Research Institute)
  • 발행 : 2009.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Ginsenosides, one of the most well-known traditional herbal medicines, are used frequently in Korea for the treatment of cardiovascular symptoms. The effects of ginseng saponin on ischemia-induced isolated rat heart were investigated through analyses of hemodynamic changes including perfusion pressure, aortic flow, coronary flow, and cardiac output. Isolated rat hearts were perfused and then subjected to 30 min of global ischemia followed by 60 min of reperfusion with modified Kreb's Henseleit solution. Myocardial contractile function was continuously recorded. Ginseng saponin administered before inducing ischemia significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output. The ginseng saponin administered group significantly recovered all of the hemodynamic parameters, except heart rate, after ischemia-reperfusion (I/R) compared with ischemia control. The intracellular calcium ($[Ca^{2+}]_i$) content in rat neonatal cardiomyocytes was quantitatively determined. Administration of ginseng saponin significantly prevented $[Ca^{2+}]_i$ increase that had been induced by simulated I/R in vitro (p<0.01) in a dose-dependent manner, suggesting that the cardioprotection of ginseng saponin is mediated by the inhibition of $[Ca^{2+}]_i$ increase. Overall, we found that the administration of ginseng saponin has cardioprotective effects on the isolated rat heart after I/R injury. These results indicate that ginseng saponin has distinct cardioprotective effects in an I/R-induced rat heart.

키워드

참고문헌

  1. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N. Heart disease and stroke statistics-2008 update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117: e25- e146 (2008) https://doi.org/10.1161/CIRCULATIONAHA.107.187998
  2. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. J Am Coll Cardiol. 50: 2173-2195 (2007) https://doi.org/10.1016/j.jacc.2007.09.011
  3. Rodryguez-Sinovas A, Abdallah Y, Piper HM, Garcia- Dorado D. Reperfusion injury as a therapeutic challenge in patients with acute myocardial infarction. Heart Fail Rev. 12: 207 (2007) https://doi.org/10.1007/s10741-007-9039-9
  4. Gross GJ, Kersten JR, Warltier DC. Mechanisms of postischemic contractile dysfunction. Ann Thorac Surg. 68: 1898-1904 (1999) https://doi.org/10.1016/S0003-4975(99)01035-8
  5. Piper HM, Garcý´a-Dorado D. Prime causes of rapid cardiomyocyte death during reperfusion. Ann Thorac Surg. 68: 1913-1919 (1999) https://doi.org/10.1016/S0003-4975(99)01025-5
  6. 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 105: 2332-2336 (2002) https://doi.org/10.1161/01.CIR.0000016602.96363.36
  7. Fleming PR. A Short History of Cardiology. Amsterdam/ Atlanta, G.A. Rodopi Publishers (1997)
  8. 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 populationbased study. Circulation 117: 598-604 (2008) https://doi.org/10.1161/CIRCULATIONAHA.107.705947
  9. Heidenreich PA, McClellan M. Trends in treatment and outcomes for acute myocardial infarction: 1975-1995. Am J Med. 110: 165-174 (2001) https://doi.org/10.1016/S0002-9343(00)00712-9
  10. Luepker RV. Decline in incident coronary heart disease. Why are the rates falling? Circulation 117: 592-593 (2008) https://doi.org/10.1161/CIRCULATIONAHA.107.747477
  11. Bolli R, Becker L, Gross G, Mentzer R, Jr Balshaw D, Lathrop DA. Myocardial protection at a crossroads: the need for translation into clinical therapy. Circ Res. 95: 125-134 (2004) https://doi.org/10.1161/01.RES.0000137171.97172.d7
  12. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodeling. Nat Rev Mol., Cell. Biol. 4: 517-529 (2003) https://doi.org/10.1038/nrm1155
  13. Elz JS, Nayler WG. Contractile recovery and reperfusion-induced calcium gain after ischemia in the isolated rat heart. Lab Invest. 58: 653-659 (1988)
  14. Meissner A, Morgan JP. Contractile dysfunction and abnormal Ca2þ modulation during postischemic reperfusion in rat heart. Am J Physiol Heart Circ Physiol. 268: H100-H111 (1995)
  15. Piper HM, Garc a-Dorado D, Ovize M. A fresh look at reperfusion injury. Cardiovasc Res. 38: 291-300 (1998) https://doi.org/10.1016/S0008-6363(98)00033-9
  16. Siegmund B, Schlu¨ter KD, Piper HM. Calcium and the oxygen paradox. Cardiovasc Res. 27: 1778-1783 (1993) https://doi.org/10.1093/cvr/27.10.1778
  17. Steenbergen C, Fralix TA, Murphy E. Role of increased cytosolic free calcium concentration in myocardial ischemic injury. Basic Res Cardiol. 88: 456-470 (1993) https://doi.org/10.1007/BF00795412
  18. Hu SY. A contribution to our knowledge of ginseng. Am J Chin Med. 5: 1-23 (1977) https://doi.org/10.1142/S0192415X77000026
  19. Chang SJ, Suh JS, Jeon BH, Nam KY, Park HK. Vasorelaxing effect by protopanaxatriol and protopanaxadiol of panax ginseng in the pig coronary artery. Korean J Ginseng Sci. 18 (2): 95-101 (1994)
  20. Chen X, Gillis CN, Moalli R. Vascular effects of ginsenosides in vitro. Br J Pharmacol. 82 (2): 485-491 (1984) https://doi.org/10.1111/j.1476-5381.1984.tb10784.x
  21. Kim ND, Kang SY, Schini VB. Ginsenosides evoke endothelium- dependent vascular relaxation in rat aorta. Gen Pharmacol. 25 (6): 1071-1077 (1994) https://doi.org/10.1016/0306-3623(94)90121-X
  22. Han KH, Choe SC, Kim HS, Sohn DW, Nam KY, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW. Effect of red ginseng on blood pressure in patients with essential hypertension and white coat hypertension. Am J Chin Med. 26 (2): 199-209 (1998) https://doi.org/10.1142/S0192415X98000257
  23. Sung J, Han KH, Zo JH, Park HJ, Kim CH, Oh BH. Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am J Chin Med. 28 (2): 205- 216 (2000) https://doi.org/10.1142/S0192415X00000258
  24. Chen X, Fang YX. Experimental study of Ginsenosides on myocardial ischemia and reperfusion injury. Natl Med J China 67: 581-583 (1987)
  25. Chen X. Cardiovascular protection by Ginsenosides and their nitric oxide relaxing action. Clin Exp Pharmacol Physiol. 23: 728-732 (1996) https://doi.org/10.1111/j.1440-1681.1996.tb01767.x
  26. Fang YX, Shen N, Chen X. Beneficial changes in prostacyclin and thromboxane Aby Ginsenosides in myocardial infarction and reperfusion injury of dogs. Acta Pharmacol Sin. 7: 222-226 (1986)
  27. Gillis CN. Biochem. Panax ginseng pharmacology: anitric oxide link? Pharmacol. 54: 1-8 (1997) https://doi.org/10.1159/000139463
  28. Kang SY, Schini-Kerth VB, Kim ND. Ginsenosides of propanaxatraol group cause endothelium-dependent relaxation in the rat aorta. Life Sci. 56: 1577-1586 (1995) https://doi.org/10.1016/0024-3205(95)00124-O
  29. Yang BC, Li YJ, Chen X. Correlation between protective effect of Ginsenosides against myocardial ischemia and lipid peroxidation in rats. Asian Pac J Pharmacol. 4: 265-272 (1989)
  30. Zhan Y, Xu XH, Jiang YP. Effects of Ginsenosides on myocardial ischemia/reperfusion damage in open-heart Surgery patients. Med J China 74: 626-628 (1994)
  31. Zhang JM, Zhao HX, Song XL, Wang Y, Jiang DW, Wang XP, Xuan WG. Study on the Effects of Ginsenosides on Global Ischemia/Reperfusion Damage. Chinese J Thorac Cardiovasc Surg. (Supplement): 105-108 (1990)
  32. Yang Y, Hu SJ, Li L, Chen GP. Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in isolated rat hearts. Acta Pharmacol Sin (1): 54-60 (2009)
  33. Li XS, Uriuda Y, Wang QD, Norlander R, Sjoquist PO, 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) https://doi.org/10.1046/j.1365-201X.1996.432152000.x
  34. Tiejun Wu, Heping Zhou, Zhenxiao Jin, Shenghui Bi, Xiuling Yang, Dinghua Yi. Weiyong Liu Cardioprotection of salidroside from ischemia/reperfusion injury by increasing Nacetylglucosamine linkage to cellular proteins. Europ J Pharm. 613: 93-99. (2009) https://doi.org/10.1016/j.ejphar.2009.04.012
  35. Hallett MB, Hodges R, Cadman M, Blanchfield H, Dewitt S, Pettit EJ, Laffafian I, Davies EV. Techniques for measuring and manipulating free $Ca^{2+}$ in the cytosol and organelles of neutrophils. J Immunol Methods 232: 77-88 (1999) https://doi.org/10.1016/S0022-1759(99)00167-2
  36. Jovanovic A, Alekseev AE, Lopez JR, Shen Wk, Terzic A. Adenosine prevents hyperkalemia-induced calcium loading in cardiac cells: relevance for cardioplegia. Ann Thorac Surg. 63: 153-161 (1997) https://doi.org/10.1016/S0003-4975(96)00769-2
  37. Kim JH, Kim S, Yoon IS, Lee JW, Jang BJ, Jeong SM, Lee JH, Lee BH, Han JS, Oh S, Kim HC, Park TK, Rhim H, Nah SY. Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. Neuropharmacol. 48: 743-756 (2005) https://doi.org/10.1016/j.neuropharm.2004.12.013
  38. Yu XC, Wu S, Wang GY, Shan J, Wong TM, Chen CF, Pang KT. 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) https://doi.org/10.1016/S0024-3205(01)01067-0
  39. Galagudza M, Kurapeev D, Minasian S, Valen G, Vaage J. Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm. Eur J Cardiothorac Surg. 25: 1006-1010 (2004) https://doi.org/10.1016/j.ejcts.2004.02.003
  40. 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. 374: 92-97 (2005) https://doi.org/10.1016/j.neulet.2004.10.030
  41. Shen L, Zhang J. Ginsenoside Rg1 increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils. Neurosci Lett. 344: 1-4 (2003) https://doi.org/10.1016/S0304-3940(03)00318-5
  42. Zhang B, Matsuda S, Tanaka J, Tateishi N, Maeda N, Wen TC, Peng H, Sakanaka M. Ginsenoside Rb(1) prevents image navigation disability, cortical infarction, and thalamic degeneration in rats with focal cerebral ischemia. J Stroke. Cerebrovasc Dis. 7: 1-9 (1998) https://doi.org/10.1016/S1052-3057(98)80015-3
  43. Bak I, Lekli I, Juhasz B, Nagy N, Varga E, Varadi J, Gesztelyi R, Szabo G, Szendrei L, Bacskay I, Vecsernyes M, Antal M, Fesus L, Boucher F, de Leiris J, Tosaki A. Cardioprotective mechanisms of Prunus cerasus (Sour cherry) seed extract against ischemia-reperfusioninduced change in isolated rat hearts. Am J Physiol Circ Physiol. 291: H1329- H1336 (2006) https://doi.org/10.1152/ajpheart.01243.2005
  44. Hearse DJ, Sutherland FJ. Experimental models for the study of cardiovascular function and disease. Pharmacol Res. 41: 597-603 (2000) https://doi.org/10.1006/phrs.1999.0651
  45. Kang M, Kim JH, ChoC, Chung HS, Kang CW, Kim Y, Shin M, Hong M, Bae H. Anti-ischemic effect of Aurantii Fructus on contractile dysfunction of ischemic and reperfused rat heart. J Ethnopharm . 111: 584-591 (2007) https://doi.org/10.1016/j.jep.2007.01.007
  46. Asano G, Takashi E, Ishiwata T, Onda M, Yokoyama M, Naito Z, Ashraf M, Sugisaki Y. Pathogenesis and protection of ischemia and reperfusion injury in myocardium. J Nippon Med Sch. 70: 384-392 (2003) https://doi.org/10.1272/jnms.70.384
  47. Barba I, Chavarria L, Ruiz-Meana M, Mirabet M, Agullo E, Garcia-Dorado D. Effect of intracellular lipid droplets on cytosolic $Ca^{2+}$ and cell death during ischaemia-reperfusion injury in cardiomyocytes. J Physiol. 587(Pt 6):1331-1341 (2009) https://doi.org/10.1113/jphysiol.2008.163311
  48. Kim S, Nah SY, Rhim H. Neuroprotective effects of ginseng saponins against L-type $Ca^{2+}$ channel-mediated cell death in rat cortical neurons. Biochem Biophys Res Commun. 365(3): 399-405 (2008) https://doi.org/10.1016/j.bbrc.2007.10.048

피인용 문헌

  1. Korean Red Ginseng Induced Cardioprotection against Myocardial Ischemia in Guinea Pig vol.17, pp.4, 2013, https://doi.org/10.4196/kjpp.2013.17.4.283