Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Processed Panax ginseng, Sun Ginseng, Decreases Oxidative Damage Induced by tert-butyl Hydroperoxide via Regulation of Antioxidant Enzyme and Anti-apoptotic Molecules in HepG2 Cells

  • Lee, Hye-Jin (Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University) ;
  • Kim, Jin-Hee (Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University) ;
  • Lee, Seo-Young (College of Pharmacy, Seoul National University) ;
  • Park, Jeong-Hill (College of Pharmacy, Seoul National University) ;
  • Hwang, Gwi-Seo (Lab of Cell Differentiation Research, College of Oriental Medicine, Gachon University)
  • Received : 2012.02.21
  • Accepted : 2012.04.03
  • Published : 2012.07.15
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Abstract

Potential antioxidant effect of processed ginseng (sun ginseng, SG) on oxidative stress generated by tert-butyl hydroperoxide (t-BHP) was investigated in HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase (LDH) leakage test demonstrated that SG dose-dependently prevents a loss of cell viability against t-BHP-induced oxidative stress. Also, SG treatment dose-dependently relieved the increment of activities of hepatic enzymes, such as aspartate aminotrasferase and alanine aminotransferase, and lipid peroxidation mediated by t-BHP treatment in HepG2 cells. SG increased the gene expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. However, high dose of SG treatment caused decrease in mRNA level of glutathione peroxidase as compared to low dosage of SG-treated cells. The gene expression of glutathione reductase was found to be slightly increased by SG treatment. In addition, SG extract attributed its hepaprotective effect by inducing the mRNA level of bcl-2 and bcl-xL but reducing that of bax. But, the gene expression of bad showed no significant change in SG-treated HepG2 cells. These findings suggest that SG has hepatoprotective effect by showing reduction of LDH release, activities of hepatic enzymes and lipid peroxidation and regulating the gene expression of antioxidant enzymes and apoptosis-related molecules against oxdative stress caused by t-BHP in HepG2 cells.

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References

  1. Vitaglione P, Morisco F, Caporaso N, Fogliano V. Dietary antioxidant compounds and liver health. Crit Rev Food Sci Nutr 2004;44:575-586.
  2. Adachi M, Ishii H. Role of mitochondria in alcoholic liver injury. Free Radic Biol Med 2002;32:487-491. https://doi.org/10.1016/S0891-5849(02)00740-2
  3. Kim HJ, Chae IG, Lee SG, Jeong HJ, Lee EJ, Lee IS. Effects of Fermented Red Ginseng Extracts on Hyperglycemia in Streptozotocin-induced Diabetic Rats. J Ginseng Res 2010;34:104-112. https://doi.org/10.5142/jgr.2010.34.2.104
  4. Hur MH, Lee MS, Yang HJ, Kim C, Bae IL, Ernst E. Ginseng for Reducing the Blood Pressure in Patients with Hypertension: A Systematic Review and Meta-Analysis. J Ginseng Res 2010;34:342-347. https://doi.org/10.5142/jgr.2010.34.4.342
  5. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod 2000;63:1702-1704. https://doi.org/10.1021/np990152b
  6. Song KC, Chang TS, Lee H, Kim J, Park JH, Hwang GS. Processed Panax ginseng, sun ginseng increases type I collagen by regulating MMP-1 and TIMP-1 expression in human dermal fi broblasts. J Ginseng Res 2012;36:61-67. https://doi.org/10.5142/jgr.2012.36.1.61
  7. Luo JZ, Luo L. American ginseng stimulates insulin production and prevents apoptosis through regulation of uncoupling protein-2 in cultured beta cells. Evid Based Complement Alternat Med 2006;3:365-372. https://doi.org/10.1093/ecam/nel026
  8. Voces J, Alvarez AI, Vila L, Ferrando A, Cabral de Oliveira C, Prieto JG. Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1999;123:175-184. https://doi.org/10.1016/S0742-8413(99)00025-0
  9. Kim HJ, Chun YJ, Park JD, Kim SI, Roh JK, Jeong TC. Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Med 1997;63:415-418. https://doi.org/10.1055/s-2006-957724
  10. Park IH, Piao LZ, Kwon SW, Lee YJ, Cho SY, Park MK, Park JH. Cytotoxic dammarane glycosides from processed ginseng. Chem Pharm Bull (Tokyo) 2002;50:538-540. https://doi.org/10.1248/cpb.50.538
  11. Baek SH, Piao XL, Lee UJ, Kim HY, Park JH. Reduction of cisplatin-induced nephrotoxicity by ginsenosides isolated from processed ginseng in cultured renal tubular cells. Biol Pharm Bull 2006;29:2051-2055. https://doi.org/10.1248/bpb.29.2051
  12. Lee JG, Lee YY, Kim SY, Pyo JS, Yun-Choi HS, Park JH. Platelet antiaggregating activity of ginsenosides isolated from processed ginseng. Pharmazie 2009;64:602-604.
  13. Kang KS, Yamabe N, Kim HY, Park JH, Yokozawa T. Effects of heat-processed ginseng and its active component ginsenoside 20(S)-Rg3 on the progression of renal damage and dysfunction in type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats. Biol Pharm Bull 2010;33:1077-1081. https://doi.org/10.1248/bpb.33.1077
  14. Sarkar MK, Sil PC. Prevention of tertiary butyl hydroperoxide induced oxidative impairment and cell death by a novel antioxidant protein molecule isolated from the herb, Phyllanthus niruri. Toxicol In Vitro 2010;24:1711-1719. https://doi.org/10.1016/j.tiv.2010.05.014
  15. Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Phenolic compounds protect HepG2 cells from oxidative damage: relevance of glutathione levels. Life Sci 2006;79:2056-2068. https://doi.org/10.1016/j.lfs.2006.06.042
  16. Lima CF, Valentao PC, Andrade PB, Seabra RM, Fernandes- Ferreira M, Pereira-Wilson C. Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage. Chem Biol Interact 2007;167:107-115. https://doi.org/10.1016/j.cbi.2007.01.020
  17. Kang KS, Yamabe N, Kim HY, Yokozawa T. Effect of sun ginseng methanol extract on lipopolysaccharide-induced liver injury in rats. Phytomedicine 2007;14:840-845. https://doi.org/10.1016/j.phymed.2007.01.002
  18. Lee HU, Bae EA, Han MJ, Kim DH. Hepatoprotective effect of 20(S)-ginsenosides Rg3 and its metabolite 20(S)-ginsenoside Rh2 on tert-butyl hydroperoxide-induced liver injury. Biol Pharm Bull 2005;28:1992-1994. https://doi.org/10.1248/bpb.28.1992
  19. Jeong TC, Kim HJ, Park JI, Ha CS, Park JD, Kim SI, Roh JK. Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats. Planta Med 1997;63:136-140. https://doi.org/10.1055/s-2006-957630
  20. Fernandes ER, Carvalho FD, Remiao FG, Bastos ML, Pinto MM, Gottlieb OR. Hepatoprotective activity of xanthones and xanthonolignoids against tert-butylhydroperoxide-induced toxicity in isolated rat hepatocytes: comparison with silybin. Pharm Res 1995;12:1756-1760. https://doi.org/10.1023/A:1016230125496
  21. Vidyashankar S, Mitra SK, Nandakumar KS. Liv.52 protects HepG2 cells from oxidative damage induced by tertbutyl hydroperoxide. Mol Cell Biochem 2010;333:41-48. https://doi.org/10.1007/s11010-009-0202-6
  22. Nicotera P, McConkey D, Svensson SA, Bellomo G, Orrenius S. Correlation between cytosolic $Ca^{2+}$ concentration and cytotoxicity in hepatocytes exposed to oxidative stress. Toxicology 1988;52:55-63. https://doi.org/10.1016/0300-483X(88)90196-5
  23. Martin C, Martinez R, Navarro R, Ruiz-Sanz JI, Lacort M, Ruiz-Larrea MB. tert-butyl hydroperoxide-induced lipid signaling in hepatocytes: involvement of glutathione and free radicals. Biochem Pharmacol 2001;62:705-712. https://doi.org/10.1016/S0006-2952(01)00704-3
  24. Lima CF, Andrade PB, Seabra RM, Fernandes-Ferreira M, Pereira-Wilson C. The drinking of a Salvia offi cinalis infusion improves liver antioxidant status in mice and rats. J Ethnopharmacol 2005;97:383-389. https://doi.org/10.1016/j.jep.2004.11.029
  25. Noh JR, Gang GT, Kim YH, Yang KJ, Lee CH, Na OS, Kim GJ, Oh WK, Lee YD. Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells. Nutr Res Pract 2010;4:3-10. https://doi.org/10.4162/nrp.2010.4.1.3
  26. Sies H. Strategies of antioxidant defense. Eur J Biochem 1993;215:213-219. https://doi.org/10.1111/j.1432-1033.1993.tb18025.x
  27. Lee M, Sorn S, Baek S, Jang S, Kim S. Antioxidant and apoptotic effects of Korean white ginseng extracted with the same ratio of protopanaxadiol and protopanaxatriol saponins in human hepatoma HepG2 cells. Ann N Y Acad Sci 2009;1171:217-227. https://doi.org/10.1111/j.1749-6632.2009.04918.x
  28. Hix S, Kadiiska MB, Mason RP, Augusto O. In vivo metabolism of tert-butyl hydroperoxide to methyl radicals. EPR spin-trapping and DNA methylation studies. Chem Res Toxicol 2000;13:1056-1064. https://doi.org/10.1021/tx000130l
  29. Byrne AM, Lemasters JJ, Nieminen AL. Contribution of increased mitochondrial free Ca2+ to the mitochondrial permeability transition induced by tert-butylhydroperoxide in rat hepatocytes. Hepatology 1999;29:1523-1531. https://doi.org/10.1002/hep.510290521
  30. Kim EH, Lee MJ, Kim IH, Pyo S, Choi KT, Rhee DK. Anti-apoptotic effects of red ginseng on oxidative stress induced by hydrogen peroxide in SK-N-SH cells. J Ginseng Res 2010;34:138-144. https://doi.org/10.5142/jgr.2010.34.2.138

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