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Preventive effect of fermented black ginseng against cisplatin-induced nephrotoxicity in rats

  • Jung, Kiwon (College of Pharmacy, CHA University) ;
  • An, Jun Min (GINSENG BY PHARM Co., Ltd.) ;
  • Eom, Dae-Woon (Department of Pathology, University of Ulsan College of Medicine, Gangneung Asan Hospital) ;
  • Kang, Ki Sung (College of Korean Medicine, Gachon University) ;
  • Kim, Su-Nam (Natural Products Research Institute, Korea Institute of Science and Technology)
  • Received : 2015.09.18
  • Accepted : 2016.03.02
  • Published : 2017.04.15

Abstract

Background: Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. Methods: The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protective effect against cisplatin-induced renal damage was tested in rats. FBG was orally administered every day at a dose of 150 mg/kg body weight for 10 d, and a single dose of cisplatin was administered intraperitoneally (7.5 mg/kg body weight) with 0.9% saline on the $4^{th}$ d. Results: The DPPH radical-scavenging activity of FBG ($IC_{50}=384{\mu}g/mL$) was stronger than that of raw ginseng. The improved DPPH radical-scavenging activity was mediated by the generation phenolic compounds. The decreased cell viability by cisplatin was recovered significantly after treatment with FBG in a dose-dependent manner. Then, the protective effect of FBG on cisplatin-induced oxidative renal damage was investigated in rats. The decreased creatinine clearance levels, which are a reliable marker for renal dysfunction in cisplatin-treated rats, were reduced to the normal level after the administration of FBG. Moreover, FBG showed protective effects against cisplatin-induced oxidative renal damage in rats through the inhibition of $NF-{\kappa}B/p65$, COX-2, and caspase-3 activation. Conclusion: These results collectively show that the therapeutic evidence for FBG ameliorates the nephrotoxicity via regulating oxidative stress, inflammation, and apoptosis.

Keywords

References

  1. Gesler WM. Therapeutic landscapes: medical issues in light of the new cultural geography. Soc Sci Med 1992;34:735-46. https://doi.org/10.1016/0277-9536(92)90360-3
  2. Wojcikowski K, Johnson DW, Gobe G. Medicinal herbal extracts-renal friend or foe?: Part two. Herbal extracts with potential renal benefits. Nephrology 2004;9:400-5. https://doi.org/10.1111/j.1440-1797.2004.00355.x
  3. Ceylan-Isik AF, Fliethman RM, Wold LE, Ren J. Herbal and traditional Chinese medicine for the treatment of cardiovascular complications in diabetes mellitus. Curr Diabetes Rev 2008;4:320-8. https://doi.org/10.2174/157339908786241142
  4. Li X, Hassoun HT, Santora R, Rabb H. Organ crosstalk: the role of the kidney. Curr Opin Crit Care 2009;15:481-7. https://doi.org/10.1097/MCC.0b013e328332f69e
  5. Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 2008;57:1446-54. https://doi.org/10.2337/db08-0057
  6. Nistala R, Whaley-Connell A, Sowers JR. Redox control of renal function and hypertension. Antioxid Redox Signal 2008;10:2047-89. https://doi.org/10.1089/ars.2008.2034
  7. Heyman SN, Rosen S, Rosenberger C. A role for oxidative stress. Contrib Nephrol 2011;174:138-48.
  8. Manucha W, Valles PG. Apoptosis modulated by oxidative stress and inflammation during obstructive nephropathy. Inflamm Allergy Drug Targets 2012;11:303-12. https://doi.org/10.2174/187152812800958997
  9. Ozbek E. Induction of oxidative stress in kidney. Int J Nephrol 2012;2012:465897.
  10. Li JM, Shah AM. ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. J Am Soc Nephrol 2003;14:S221-6. https://doi.org/10.1097/01.ASN.0000077406.67663.E7
  11. Gokhan SH. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010;140:900-17. https://doi.org/10.1016/j.cell.2010.02.034
  12. Chung HW, Lim JH, Kim MY, Shin SJ, Chung S, Choi BS, Kim HW, Kim YS, Park CW, Chang YS. High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the $PPAR{\alpha}-FoxO3a-PGC-1{\alpha}$ pathway. Nephrol Dial Transplant 2012;27:2213-25. https://doi.org/10.1093/ndt/gfr613
  13. Lim JH, Kim EN, Kim MY, Chung S, Shin SJ, Kim HW, Yang CW, Kim YS, Chang YS, Park CW, et al. Age-associated molecular changes in the kidney in aged mice. Oxid Med Cell Longev 2012;2012:171383.
  14. Mathushima H, Yonemura K, Ohishi K, Hishida A. The role of oxygen free radicals in cisplatin-induced acute renal failure in rats. J Lab Clin Med 1998;131:518-26. https://doi.org/10.1016/S0022-2143(98)90060-9
  15. Kaushal GP, Kaushal V, Hong X, Shah SV. Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Kidney Int 2001;60:1726-36. https://doi.org/10.1046/j.1523-1755.2001.00026.x
  16. Basnakian AG, Apostolov EO, Yin X, Napirei M, Mannherz HG, Shah SV. Cisplatin nephrotoxicity is mediated by deoxyribonuclease I. J Am Soc Nephrol 2005;16:697-702. https://doi.org/10.1681/ASN.2004060494
  17. Mitazaki S, Honma S, Suto M, Kato N, Hiraiwa K, Yoshida M, Abe S. Interleukin-6 plays a protective role in development of cisplatin-induced acute renal failure through upregulation of anti-oxidative stress factors. Life Sci 2011;88:1142-8. https://doi.org/10.1016/j.lfs.2011.04.016
  18. Yang F, Long W, Xuechuan H, Xueqin L, Hongyun M, Yonghui D. Upregulation of Fas in epithelial ovarian cancer reverses the development of resistance to cisplatin. BMB Rep 2015;48:30-5. https://doi.org/10.5483/BMBRep.2015.48.1.042
  19. Kitagawa I, Taniyama T, Shibuya H, Noda T, Yoshikawa M. Chemical studies on crude drug processing: V. On the constituents of ginseng radix rubra (2): comparison of the constituents of white ginseng and red ginseng prepared from the same Panax ginseng root. Yakugaku Zasshi 1987;107:495-505. https://doi.org/10.1248/yakushi1947.107.7_495
  20. Wang CZ, Zhang B, Song WX, Wang A, Ni M, Luo X, Aung HH, Xie JT, Tong R, He TC, et al. Steamed American ginseng berry: ginsenoside analyses and anticancer activities. J Agric Food Chem 2006;54:9936-42. https://doi.org/10.1021/jf062467k
  21. Kang KS, Kim HY, Baek SH, Yoo HH, Park JH, Yokozawa T. Study on the hydroxyl radical scavenging activity changes of ginseng and ginsenoside-Rb2 by heat processing. Biol Pharm Bull 2007;30:724-8. https://doi.org/10.1248/bpb.30.724
  22. Bak MJ, Jeong WS, Kim KB. Detoxifying effect of fermented black ginseng on $H_2O_2$-induced oxidative stress in HepG2 cells. Int J Mol Med 2014;34:1516-22. https://doi.org/10.3892/ijmm.2014.1972
  23. Lee W, Park SH, Lee S, Chung BC, Song MO, Song KI, Ham J, Kim SN, Kang KS. Increase in antioxidant effect of ginsenoside Reealanine mixture by Maillard reaction. Food Chem 2012;135:2430-5. https://doi.org/10.1016/j.foodchem.2012.06.108
  24. Kaneko H, Nakanishi K. Proof of the mysterious efficacy of ginseng; basic and clinical trials: clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J Pharmacol Sci 2004;95:158-62. https://doi.org/10.1254/jphs.FMJ04001X5
  25. Kang KS, Yamabe N, Kim HY, Park JH, Yokozawa T. Therapeutic potential of 20(S)-ginsenoside Rg3 against streptozotocin-induced diabetic renal damage in rats. Eur J Pharmacol 2008;591:266-72. https://doi.org/10.1016/j.ejphar.2008.06.077
  26. Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean red ginseng. Mediators Inflamm 2012;2012:732860.
  27. Ramesh T, Kim SW, Hwang SY, Sohn SH, Yoo SK, Kim SK. Panax ginseng reduces oxidative stress and restores antioxidant capacity in aged rats. Nutr Res 2012;32:718-26. https://doi.org/10.1016/j.nutres.2012.08.005
  28. Park HJ, Shim HS, Kim KS, Shim I. The protective effect of black ginseng against transient focal ischemia-induced neuronal damage in rats. Korean J Physiol Pharmacol 2011;15:333-8. https://doi.org/10.4196/kjpp.2011.15.6.333
  29. Lee HS, Kim MR, Park Y, Park HJ, Chang UJ, Kim SY, Suh HJ. Fermenting red ginseng enhances its safety and efficacy as a novel skin care anti-aging ingredient: in vitro and animal study. J Med Food 2012;15:1015-23. https://doi.org/10.1089/jmf.2012.2187
  30. Singleton VL, Orthofer R, Lamuela-Raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of FolineCiocalteu reagent. Methods Enzymol 1999;299:152-78.
  31. Hatano T, Edamatsu R, Hiramatsu M, Mori A, Fujita Y, Yasuhara T, Yoshida T, Okuda T. Effects of the interaction of tannins with co-existing substances: VI. Effects of tannins and related polyphenols on superoxide anion radical, and on 1,1-diphenyl-2-picrylhydrazyl radical. Chem Pharm Bull 1989;37:2016-21. https://doi.org/10.1248/cpb.37.2016
  32. Park JY, Choi P, Kim T, Ko H, Kim HK, Kang KS, Ham J. Protective effects of processed ginseng and its active ginsenosides on cisplatin-induced nephrotoxicity: in vitro and in vivo studies. J Agric Food Chem 2015;63:5964-9. https://doi.org/10.1021/acs.jafc.5b00782
  33. Han MS, Han IH, Lee D, An JM, Kim SN, Shin MS, Yamabe N, Hwang GS, Yoo HH, Choi SJ, et al. Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells. J Ginseng Res 2017;42(2):135-40.
  34. Oh JS, Lee SR, Hwang KT, Ji GE. The anti-obesity effects of the dietary combination of fermented red ginseng with levan in high fat diet mouse model. Phytother Res 2014;28(4):617-22. https://doi.org/10.1002/ptr.5042
  35. Takeda H, Sadakane C, Hattori T, Katsurada T, Ohkawara T, Nagai K, Asaka M. Rikkunshito, an herbal medicine, suppresses cisplatin-induced anorexia in rats via 5-HT2 receptor antagonism. Gastroenterology 2008;134:2004-13. https://doi.org/10.1053/j.gastro.2008.02.078
  36. Kang KS, Ham J, Kim YJ, Park JH, Cho EJ, Yamabe N. Heat-processed Panax ginseng and diabetic renal damage: active components and action mechanism. J Ginseng Res 2013;37:379-88. https://doi.org/10.5142/jgr.2013.37.379
  37. Yamabe N, Kim YJ, Lee S, Cho EJ, Park SH, Ham J, Kim HY, Kang KS. Increase in antioxidant and anticancer effects of ginsenoside Reelysine mixture by Maillard reaction. Food Chem 2013;138:876-83. https://doi.org/10.1016/j.foodchem.2012.12.004
  38. Park JY, Choi P, Kim HK, Kang KS, Ham J. Increase in apoptotic effect of Panax ginseng by microwave processing in human prostate cancer cells: in vitro and in vivo studies. J Ginseng Res 2016;40:62-7. https://doi.org/10.1016/j.jgr.2015.04.007
  39. Zhu QY, Hackman RM, Ensunsa JL, Holt RR, Keen CL. Antioxidant activities of oolong tea. J Agric Food Chem 2002;50:6929-34. https://doi.org/10.1021/jf0206163
  40. Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci 2004;74:2157-84. https://doi.org/10.1016/j.lfs.2003.09.047
  41. Tortorici MA, Nolin TD. Kidney function assessment and its role in drug development, review and utilization. Expert Rev Clin Pharmacol 2014;7:523-32. https://doi.org/10.1586/17512433.2014.922865
  42. Bratton SB, Cohen GM. Apoptotic death sensor: an organelle's alter ego? Trends Pharmacol Sci 2001;22:306-15. https://doi.org/10.1016/S0165-6147(00)01718-1
  43. Razzaque MS. Cisplatin nephropathy: is cytotoxicity avoidable? Nephrol Dial Transplant 2007;22:2112-6. https://doi.org/10.1093/ndt/gfm378
  44. Domitrovic R, Cvijanovic O, Pugel EP, Zagorac GB, Mahmutefendic H, Skoda M. Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney. Toxicology 2013;310:115-23. https://doi.org/10.1016/j.tox.2013.05.015

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