DOI QR코드

DOI QR Code

Chronic dietary ginseng extract administration ameliorates antioxidant and cholinergic systems in the brains of aged mice

  • Lee, Mi Ra (Korea Institute of Oriental Medicine) ;
  • Ma, Jin Yeul (Korea Institute of Oriental Medicine) ;
  • Sung, Chang Keun (Department of Food Science and Technology, Chungnam National University)
  • Received : 2017.01.23
  • Accepted : 2017.06.15
  • Published : 2017.10.15

Abstract

Background: Black ginseng has a more potent biological activity than non-steamed ginseng. We investigated the effects of long-term intake of dietary black ginseng extract (BG) on antioxidant activity in aged mice. We also compared the effects of BG on cognitive deficits with those of white ginseng extract (WG) and red ginseng extract (RG). Methods: Ten-month-old mice were fed an AIN-93G-based diet containing 10 g/kg (low dose, L) or 30 g/kg (high dose, H) WG powder, RG powder, or BG powder for 24 wk. We measured serum lipids, the activities of antioxidant enzymes, and malondialdehyde levels. Additionally, the protein expression levels of choline acetyltransferase and vesicular acetylcholine transporter, which are presynaptic cholinergic markers in the cortex and hippocampus of the brain, were measured by western blotting. Results: Triglyceride levels were reduced in all the extract-treated mice, except those in the LBG group. High-density lipoprotein cholesterol levels in the HBG group were higher than those in the control group. Total cholesterol levels were reduced in the LBG group. Additionally, glucose levels in the HBG group were significantly reduced by 41.2%. There were lower levels of malondialdehyde in the LBG group than in the control group. Furthermore, glutathione reductase activity increased in the HWG group and the HRG group. The protein expression levels of choline acetyltransferase and vesicular acetylcholine transporter significantly increased in all the ginseng-treated groups. Conclusion: The results suggest that supplementation with the tested ginseng extracts may suppress the cognitive decline associated with aging, via regulation of the cholinergic and antioxidant defense systems.

Keywords

References

  1. Osiewacz HD, Hamann A. DNA reorganization and biological aging. A review. Biochemistry (Mosc) 1997;62:1275-84.
  2. Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C. New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 2010;123:2533-42. https://doi.org/10.1242/jcs.070490
  3. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956;11:298-300. https://doi.org/10.1093/geronj/11.3.298
  4. Berry A, Greco A, Giorgio M, Pelicci PG, de Kloet R, Alleva E, Minghetti L, Cirulli F. Deletion of the lifespan determinant p66(Shc) improves performance in a spatial memory task, decreases levels of oxidative stress markers in the hippocampus and increases levels of the neurotrophin BDNF in adult mice. Exp Gerontol 2008;43:200-8. https://doi.org/10.1016/j.exger.2007.10.016
  5. Duffy KB, Spangler EL, Devan BD, Guo Z, Bowker JL, Janas AM, Hagepanos A, Minor RK, DeCabo R, Mouton PR, et al. A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol Aging 2008;29:1680-9. https://doi.org/10.1016/j.neurobiolaging.2007.04.002
  6. Bourin M, Ripoll N, Dailly E. Nicotinic receptors and Alzheimer's disease. Curr Med Res Opin 2003;19:169-77. https://doi.org/10.1185/030079903125001631
  7. Voytko ML, Olton DS, Richardson RT, Gorman LK, Tobin JR, Price DL. Basal forebrain lesions in monkeys disrupt attention but not learning and memory. J Neurosci 1994;14:167-86. https://doi.org/10.1523/JNEUROSCI.14-01-00167.1994
  8. DeKosky ST, Harbaugh RE, Schmitt FA, Bakay RA, Chui HC, Knopman DS, Reeder TM, Shetter AG, Senter HJ, Markesbery WR. Cortical biopsy in Alzheimer's disease: diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Intraventricular bethanecol study group. Ann Neurol 1992;32:625-32. https://doi.org/10.1002/ana.410320505
  9. Shukitt-Hale B, Lau FC, Joseph JA. Berry fruit supplementation and the aging brain. J Agric Food Chem 2008;56:636-41. https://doi.org/10.1021/jf072505f
  10. 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
  11. O'Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med 1998;7:523-36. https://doi.org/10.1001/archfami.7.6.523
  12. Sun BS, Gu LJ, Fang ZM, Wang CY, Wang Z, Lee MR, Li Z, Li JJ, Sung CK. Simultaneous quantification of 19 ginsenosides in black ginseng developed from Panax ginseng by HPLC-ELSD. J Pharm Biomed Anal 2009;15:15-22.
  13. Wan JY, Fan Y, Yu QT, Ge YZ, Yan CP, Alolga RN, Li P, Ma ZH, Qi LW. Integrated evaluation of malonyl ginsenosides, amino acids and polysaccharides in fresh and processed ginseng. J Pharm Biomed Anal 2015;107:89-97. https://doi.org/10.1016/j.jpba.2014.11.014
  14. Kang KS, Kim HY, Pyo JS, Yokozawa T. Increase in the free radical scavenging activity of ginseng by heat-processing. Biol Pharm Bull 2006;29:750-4. https://doi.org/10.1248/bpb.29.750
  15. Kim SJ, Kim AK. Anti-breast cancer activity of fine black ginseng (Panax ginseng Meyer) and ginsenoside Rg5. J Ginseng Res 2015;39:125-34. https://doi.org/10.1016/j.jgr.2014.09.003
  16. Lee MR, Yun BS, In OH, Sung CK. Comparative study of Korean white, red, and black ginseng extract on cholinesterase inhibitory activity and cholinergic function. J Ginseng Res 2011;35:421-8. https://doi.org/10.5142/jgr.2011.35.4.421
  17. Lee Y, Oh S. Administration of red ginseng ameliorates memory decline in aged mice. J Ginseng Res 2015;39:250-6. https://doi.org/10.1016/j.jgr.2015.01.003
  18. Zhao HF, Li Q, Li Y. Long-term ginsenoside administration prevents memory loss in aged female C57BL/6J mice by modulating the redox status and up-regulating the plasticity-related proteins in hippocampus. Neuroscience 2011;183:189-202. https://doi.org/10.1016/j.neuroscience.2011.03.048
  19. Heo JH, Lee ST, Oh MJ, Park HJ, Shim JY, Chu K, Kim M. Improvement of cognitive deficit in Alzheimer's disease patients by long term treatment with Korean red ginseng. J Ginseng Res 2011;35:457-61. https://doi.org/10.5142/jgr.2011.35.4.457
  20. Lee MR, Yun BS, Liu L, Zhang DL, Wang Z, Wang CL, Gu LJ, Wang CY, Mo EK, Sung CK. Effect of black ginseng on memory improvement in the amnesic mice induced by scopolamine. J Ginseng Res 2010;34:51-8. https://doi.org/10.5142/JGR.2010.34.1.051
  21. Jung S, Lee MS, Shin Y, Kim CT, Kim IH, Kim Y. High hydrostatic pressure extract of red ginseng attenuates inflammation in rats with high-fat diet induced obesity. Prev Nutr Food Sci 2015;20:253-9. https://doi.org/10.3746/pnf.2015.20.4.253
  22. Park SJ, Lim KH, Noh JH, Jeong EJ, Kim YS, Han BC, Lee SH, Moon KS. Subacute oral toxicity study of Korean red ginseng extract in Sprague-Dawley rats. Toxicol Res 2013;29:285-92. https://doi.org/10.5487/TR.2013.29.4.285
  23. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-8. https://doi.org/10.1016/0003-2697(78)90342-1
  24. Saba E, Jeon BR, Jeong DH, Lee K, Goo YK, Kim SH, Sung CK, Roh SS, Kim SD, Kim HK, et al. Black ginseng extract ameliorates hypercholesterolemia in rats. J Ginseng Res 2016;40:160-8. https://doi.org/10.1016/j.jgr.2015.07.003
  25. Kim SH, Park KS. Effects of Panax ginseng extract on lipid metabolism in humans. Pharmacol Res 2003;48:511-3. https://doi.org/10.1016/S1043-6618(03)00189-0
  26. Hong BN, Ji MG, Kang TH. The efficacy of red ginseng in type 1 and type 2 diabetes in animals. Evid Based Complement Alternat Med 2013;2013:593181.
  27. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT, et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 2008;18:46-56. https://doi.org/10.1016/j.numecd.2006.04.003
  28. Floyd RA, Carney JM. Free radical damage to protein and DNA: Mechanism involved and relevant observations on brain undergoing oxidative stress. Ann Neurol 1992;32:S22-7. https://doi.org/10.1002/ana.410320706
  29. Arivazhagan P, Thilakavathy T, Panneerselvam C. Antioxidant lipoate and tissue antioxidants in aged rats. J Nutr Biochem 2000;13:122-7.
  30. Ramesh T, Kim SW, Sung JH, Hwang SY, Sohn SH, Yoo SK, Kim SK. Effect of fermented Panax ginseng extract (GINST) on oxidative stress and antioxidant activities in major organs of aged rats. Exp Gerontol 2012;47:77-84. https://doi.org/10.1016/j.exger.2011.10.007
  31. Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med 2016;95:27-42. https://doi.org/10.1016/j.freeradbiomed.2016.02.028
  32. Foyer CH, Theodoulou FL, Delrot S. The functions of inter- and intracellular glutathione transport systems in plants. Trends Plant Sci 2001;6:486-92. https://doi.org/10.1016/S1360-1385(01)02086-6
  33. 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;63:1702-4. https://doi.org/10.1021/np990152b
  34. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. https://doi.org/10.1016/S0006-2952(99)00212-9
  35. Gilmor ML, Counts SE, Wiley RG, Levey AI. Coordinate expression of the vesicular acetylcholine transporter and choline acetyltransferase following septohippocampal pathway lesions. J Neurochem 1998;71:2411-20.
  36. Oda Y. Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int 1999;49:921-37. https://doi.org/10.1046/j.1440-1827.1999.00977.x
  37. Kim MS, Yu JM, Kim HJ, Kim HB, Kim ST, Jang SK, Choi YW, Lee DI, Joo SS. Ginsenoside Re and Rd enhance the expression of cholinergic markers and neuronal differentiation in Neuro-2a cells. Biol Pharm Bull 2014;37:826-33. https://doi.org/10.1248/bpb.b14-00011
  38. Salim KN, McEwen BS, Chao HM. Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain. Brain Res Mol Brain Res 1997;47:177-82. https://doi.org/10.1016/S0169-328X(97)00042-9
  39. Zhang JT, Liu Y, Qu ZW, Zhang XL, Xiao HL. Influence of ginsenoside Rb1 and Rg1 on some central neurotransmitter receptors and protein biosynthesis in the mouse brain. Yao Xue Xue Bao 1988;23:12-6.
  40. Kim EJ, Jung IH, Le Van TK, Jeong JJ, Kim NJ, Kim DH. Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. J Ethnopharmacol 2013;146:294-9. https://doi.org/10.1016/j.jep.2012.12.047
  41. Bao HY, Zhang J, Yeo SJ, Myung CS, Kim HM, Kim JM, Park JH, Cho JS, Kang JS. Memory enhancing and neuroprotective effects of selected ginsenosides. Arch Pharm Res 2005;28:335-42. https://doi.org/10.1007/BF02977802

Cited by

  1. Anti-aging Effects of Ginseng and Ginsenosides on the Nervous System vol.14, pp.8, 2017, https://doi.org/10.3923/ijp.2018.1188.1197
  2. Aqueous Extract of Taegeuk Ginseng Inhibits Platelet Aggregation and Thrombus Formation vol.21, pp.11, 2018, https://doi.org/10.1089/jmf.2017.4145
  3. Black Ginseng and Ginsenoside Rb1 Promote Browning by Inducing UCP1 Expression in 3T3-L1 and Primary White Adipocytes vol.11, pp.11, 2017, https://doi.org/10.3390/nu11112747
  4. Recent progress in polysaccharides from Panax ginseng C. A. Meyer vol.12, pp.2, 2017, https://doi.org/10.1039/d0fo01896a
  5. Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults vol.13, pp.4, 2017, https://doi.org/10.3390/pharmaceutics13040487
  6. Panax Ginseng alleviates thioacetamide-induced liver injury in ovariectomized rats: Crosstalk between inflammation and oxidative stress vol.16, pp.11, 2017, https://doi.org/10.1371/journal.pone.0260507