Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Proteomic change by Korean Red Ginseng in the substantia nigra of a Parkinson's disease mouse model

  • Kim, Dongsoo (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Kwon, Sunoh (KM Fundamental Research Division, Korea Institute of Oriental Medicine) ;
  • Jeon, Hyongjun (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Ryu, Sun (Korean Medicine Research Center for Healthy Aging, Pusan National University) ;
  • Ha, Ki-Tae (Department of Korean Medical Science, School of Korean Medicine, Pusan National University) ;
  • Kim, Seungtae (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
  • Received : 2017.01.02
  • Accepted : 2017.04.24
  • Published : 2018.10.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Recent studies have shown that Korean Red Ginseng (KRG) successfully protects against dopaminergic neuronal death in the nigrostriatal pathway of a Parkinson's disease (PD) mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration; however, the mechanism has yet to be identified. Therefore, in this study we used two-dimensional electrophoresis to investigate the effects of KRG on the changes in protein expression in the substantia nigra (SN) of MPTP-treated mice. Methods: Male C57BL/6 mice (9 wk old) were intraperitoneally administered MPTP (20 mg/kg) four times at 2-h intervals, after which KRG (100 mg/kg) was orally administered once a day for 5 d. Two hours after the fifth KRG administration, a pole test was conducted to evaluate motor function, after which the brains were immediately collected. Survival of dopaminergic neurons was measured by immunohistochemistry, and protein expression was measured by two-dimensional electrophoresis and Western blotting. Results: KRG alleviated MPTP-induced behavioral dysfunction and neuronal toxicity in the SN. Additionally, the expression of eight proteins related to neuronal formation and energy metabolism for survival were shown to have changed significantly in response to MPTP treatment or KRG administration. KRG alleviated the downregulated protein expression following MPTP administration, indicating that it may enhance neuronal development and survival in the SN of MPTP-treated mice. Conclusion: These findings indicate that KRG may have therapeutic potential for the treatment of patients with PD.

Keywords

References

  1. Lima MM, Targa AD, Noseda AC, Rodrigues LS, Delattre AM, dos Santos FV, Fortes MH, Maturana MJ, Ferraz AC. Does Parkinson's disease and type-2 diabetes mellitus present common pathophysiological mechanisms and treatments? CNS Neurol Disord Drug Targets 2014;13:418-28. https://doi.org/10.2174/18715273113126660155
  2. Ali SF, Binienda ZK, Imam SZ. Molecular aspects of dopaminergic neurodegeneration: geneeenvironment interaction in parkin dysfunction. Int J Environ Res Public Health 2011;8:4702-13. https://doi.org/10.3390/ijerph8124702
  3. Kwon S, Seo BK, Kim S. Acupuncture points for treating Parkinson's disease based on animal studies. Chin J Integr Med 2016;22:723-7. https://doi.org/10.1007/s11655-016-2525-y
  4. Gerecke KM, Jiao Y, Pani A, Pagala V, Smeyne RJ. Exercise protects against MPTP-induced neurotoxicity in mice. Brain Res 2010;1341:72-83. https://doi.org/10.1016/j.brainres.2010.01.053
  5. Ma R, Sun L, Chen X, Mei B, Chang G, Wang M, Zhao D. Proteomic analyses provide novel insights into plant growth and ginsenoside biosynthesis in forest cultivated Panax ginseng (F. Ginseng). Front Plant Sci 2016;7:1.
  6. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, Kwak YS. Characterization of Korean Red Ginseng (Panax ginseng Meyer): history, preparation method, and chemical composition. J Ginseng Res 2015;39:384-91. https://doi.org/10.1016/j.jgr.2015.04.009
  7. Kim EH, Jang MH, Shin MC, Shin MS, Kim CJ. Protective effect of aqueous extract of Ginseng radix against 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 cells. Biol Pharm Bull 2003;26:1668-73. https://doi.org/10.1248/bpb.26.1668
  8. Ryu S, Koo S, Ha KT, Kim S. Neuroprotective effect of Korea Red Ginseng extract on 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 cells. Anim Cells Syst 2016;20:363-8. https://doi.org/10.1080/19768354.2016.1257510
  9. Hu SQ, Han RW, Mak SH, Han YF. Protection against 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis by water extract of ginseng (Panax ginseng CA Meyer) in SH-SY5Y cells. J Ethnopharmacol 2011;135:34-42. https://doi.org/10.1016/j.jep.2011.02.017
  10. Jun YL, Bae CH, Kim D, Koo S, Kim S. Korean Red Ginseng protects dopaminergic neurons by suppressing the cleavage of p35 to p25 in a Parkinson's disease mouse model. J Ginseng Res 2015;39:148-54. https://doi.org/10.1016/j.jgr.2014.10.003
  11. Kim D, Jeon H, Ryu S, Koo S, Ha KT, Kim S. Proteomic analysis of the effect of Korean Red Ginseng in the striatum of a Parkinson's disease mouse model. PLoS One 2016;11:e0164906. https://doi.org/10.1371/journal.pone.0164906
  12. Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, Kim M. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease. Eur J Neurol 2008;15:865-8. https://doi.org/10.1111/j.1468-1331.2008.02157.x
  13. Zhou T, Zu G, Zhang X, Wang X, Li S, Gong X, Liang Z, Zhao J. Neuroprotective effects of ginsenoside Rg1 through the Wnt/beta-catenin signaling pathway in both in vivo and in vitro models of Parkinson's disease. Neuropharmacology 2016;101:480-9. https://doi.org/10.1016/j.neuropharm.2015.10.024
  14. Heng Y, Zhang QS, Mu Z, Hu JF, Yuan YH, Chen NH. Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecidinduced parkinsonism mouse model by targeting alpha-synuclein abnormalities in the substantia nigra. Toxicol Lett 2016;243:7-21. https://doi.org/10.1016/j.toxlet.2015.12.005
  15. Liu Y, Zhang RY, Zhao J, Dong Z, Feng DY, Wu R, Shi M, Zhao G. Ginsenoside Rd protects SH-SY5Y cells against 1-methyl-4-phenylpyridinium induced Injury. Int J Mol Sci 2015;16:14395-408. https://doi.org/10.3390/ijms160714395
  16. Ardah MT, Paleologou KE, Lv G, Menon SA, Abul Khair SB, Lu JH, Safieh-Garabedian B, Al-Hayani AA, Eliezer D, Li M, et al. Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils. Neurobiol Dis 2015;74:89-101. https://doi.org/10.1016/j.nbd.2014.11.007
  17. Khoudoli GA, Porter IM, Blow JJ, Swedlow JR. Optimisation of the twodimensional gel electrophoresis protocol using the Taguchi approach. Proteome Sci 2004;2:6. https://doi.org/10.1186/1477-5956-2-6
  18. Wu Y, Zhou J, Zhang X, Zheng X, Jiang X, Shi L, Yin W, Wang J. Optimized sample preparation for two-dimensional gel electrophoresis of soluble proteins from chicken bursa of Fabricius. Proteome Sci 2009;7:38. https://doi.org/10.1186/1477-5956-7-38
  19. L'Episcopo F, Tirolo C, Caniglia S, Testa N, Serra PA, Impagnatiello F, Morale MC, Marchetti B. Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J Neuroinflammation 2010;7. 83. https://doi.org/10.1186/1742-2094-7-83
  20. Kim ST, Moon W, Chae Y, Kim YJ, Lee H, Park HJ. The effect of electroaucpuncture for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced proteomic changes in the mouse striatum. J Physiol Sci 2010;60:27-34. https://doi.org/10.1007/s12576-009-0061-7
  21. Oakley BR, Kirsch DR, Morris NR. A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels. Anal Biochem 1980;105:361-3. https://doi.org/10.1016/0003-2697(80)90470-4
  22. Roberts RG, Sheng M. Association of dystrophin-related protein 2 (DRP2) with postsynaptic densities in rat brain. Mol Cell Neurosci 2000;16:674-85. https://doi.org/10.1006/mcne.2000.0895
  23. Anand A, Tyagi R, Mohanty M, Goyal M, Silva KR, Wijekoon N. Dystrophin induced cognitive impairment: mechanisms, models and therapeutic strategies. Ann Neurosci 2015;22:108-18.
  24. Sekiguchi M, Zushida K, Yoshida M, Maekawa M, Kamichi S, Yoshida M, Sahara Y, Yuasa S, Takeda S, Wada K. A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice. Brain 2009;132:124-35. https://doi.org/10.1093/brain/awn253
  25. Yamashita N, Goshima Y. Collapsin response mediator proteins regulate neuronal development and plasticity by switching their phosphorylation status. Mol Neurobiol 2012;45:234-46. https://doi.org/10.1007/s12035-012-8242-4
  26. Fukada M, Watakabe I, Yuasa-Kawada J, Kawachi H, Kuroiwa A, Matsuda Y, Noda M. Molecular characterization of CRMP5, a novel member of the collapsin response mediator protein family. J Biol Chem 2000;275:37957-65. https://doi.org/10.1074/jbc.M003277200
  27. Quach TT, Honnorat J, Kolattukudy PE, Khanna R, Duchemin AM. CRMPs: critical molecules for neurite morphogenesis and neuropsychiatric diseases. Mol Psychiatry 2015;20:1037-45. https://doi.org/10.1038/mp.2015.77
  28. Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 2003;301:513-7. https://doi.org/10.1126/science.1083995
  29. Glombik K, Stachowicz A, Slusarczyk J, Trojan E, Budziszewska B, Suski M, Kubera M, Lason W, Wedzony K, Olszanecki R, et al. Maternal stress predicts altered biogenesis and the profile of mitochondrial proteins in the frontal cortex and hippocampus of adult offspring rats. Psychoneuroendocrinology 2015;60:151-62. https://doi.org/10.1016/j.psyneuen.2015.06.015
  30. Kirkby B, Roman N, Kobe B, Kellie S, Forwood JK. Functional and structural properties of mammalian acyl-coenzyme A thioesterases. Prog Lipid Res 2010;49:366-77. https://doi.org/10.1016/j.plipres.2010.04.001
  31. Kuramochi Y, Takagi-Sakuma M, Kitahara M, Emori R, Asaba Y, Sakaguchi R, Watanabe T, Kuroda J, Hiratsuka K, Nagae Y, et al. Characterization of mouse homolog of brain acyl-CoA hydrolase: molecular cloning and neuronal localization. Brain Res Mol Brain Res 2002;98:81-92. https://doi.org/10.1016/S0169-328X(01)00323-0
  32. Ellis JM, Wong GW, Wolfgang MJ. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity. Mol Cell Biol 2013;33:1869-82. https://doi.org/10.1128/MCB.01548-12
  33. Noh GJ, Jane Tavyev Asher Y, Graham Jr JM. Clinical review of genetic epileptic encephalopathies. Eur J Med Genet 2012;55:281-98. https://doi.org/10.1016/j.ejmg.2011.12.010
  34. Parviz M, Vogel K, Gibson KM, Pearl PL. Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 2014;3:217-27.
  35. Gupta V, Wellen KE, Mazurek S, Bamezai RN. Pyruvate kinase M2: regulatory circuits and potential for therapeutic intervention. Curr Pharm Des 2014;20:2595-606. https://doi.org/10.2174/13816128113199990484
  36. Golpich M, Amini E, Mohamed Z, Azman Ali R, Mohamed Ibrahim N, Ahmadiani A. Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: pathogenesis and treatment. CNS Neurosci Ther 2017;23:5-22. https://doi.org/10.1111/cns.12655
  37. Bentea E, Sconce MD, Churchill MJ, Van Liefferinge J, Sato H, Meshul CK, Massie A. MPTP-induced parkinsonism in mice alters striatal and nigral xCT expression but is unaffected by the genetic loss of xCT. Neurosci Lett 2015;593:1-6. https://doi.org/10.1016/j.neulet.2015.03.013
  38. Feksa LR, Cornelio A, Dutra-Filho CS, De Souza Wyse AT, Wajner M, Wannmacher CM. Inhibition of pyruvate kinase activity by cystine in brain cortex of rats. Brain Res 2004;1012:93-100. https://doi.org/10.1016/j.brainres.2004.03.035
  39. Genier S, Degrandmaison J, Moreau P, Labrecque P, Hebert TE, Parent JL. Regulation of GPCR expression through an interaction with CCT7, a subunit of the CCT/TRiC complex. Mol Biol Cell 2016;27:3800-12. https://doi.org/10.1091/mbc.e16-04-0224
  40. Liu J, Shi M, Hong Z, Zhang J, Bradner J, Quinn T, Beyer RP, McGeer PL, Chen S, Zhang J. Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by alpha-synuclein. Proteomics 2010;10:2138-50. https://doi.org/10.1002/pmic.200900745
  41. Gonzalez-Burgos E, Fernandez-Moriano C, Gomez-Serranillos MP. Potential neuroprotective activity of ginseng in Parkinson's disease: a review. J Neuroimmune Pharmacol 2015;10:14-29. https://doi.org/10.1007/s11481-014-9569-6

Cited by

  1. Korean Red Ginseng Enhances Neurogenesis in the Subventricular Zone of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Mice vol.10, pp.None, 2018, https://doi.org/10.3389/fnagi.2018.00355
  2. Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/6565396
  3. Korean red ginseng suppresses 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced inflammation in the substantia nigra and colon vol.94, pp.None, 2018, https://doi.org/10.1016/j.bbi.2021.02.028
  4. Korean red ginseng promotes hippocampal neurogenesis in mice vol.15, pp.5, 2018, https://doi.org/10.4103/1673-5374.268905