DOI QR코드

DOI QR Code

Effects of Gypenosides on Dopaminergic Neuronal Cell Death in 6-Hydroxydopamine-lesioned Rat Model of Parkinson's Disease with Long-term L-DOPA Treatment

  • Shin, Keon Sung (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Zhao, Ting Ting (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Park, Hyun Jin (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Kim, Kyung Sook (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University) ;
  • Choi, Hyun Sook (Department of Food and Nutrition, Chungcheong University) ;
  • Lee, Myung Koo (College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University)
  • Received : 2016.01.28
  • Accepted : 2016.02.29
  • Published : 2016.09.30

Abstract

The goal of this study was to determine whether gypenosides (GPS) exert protective effects against dopaminergic neuronal cell death in a 6-hydroxydopamine (OHDA)-lesioned rat model of Parkinson's disease (PD) with or without long-term 3,4-dihydroxyphenylalanine (L-DOPA) treatment. Rats were injected with 6-OHDA in the substantia nigra to induce PD-like symptoms; 14 days after injection, groups of 6-OHDA-lesioned animals were treated for 21 days with GPS (25 or 50 mg/kg) and/or L-DOPA (20 mg/kg). Dopaminergic neuronal cell death was assessed by counting tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra and measuring levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. Dopaminergic neuronal cell death induced by 6-OHDA lesions was ameliorated by GPS treatment (50 mg/kg). L-DOPA treatment exacerbated 6-OHDA-induced dopaminergic neuronal cell death; however, these effects were partially reversed by GPS treatment (25 and 50 mg/kg). These results suggest that GPS treatment is protective against dopaminergic neuronal cell death in a 6-OHDA-lesioned rat model of PD with long-term L-DOPA treatment. Therefore, GPS may be useful as a phytotherapeutic agent for the treatment of PD.

Keywords

References

  1. Fearnley, J. M.; Lees, A. J. Brain 1991, 114, 2283-2301. https://doi.org/10.1093/brain/114.5.2283
  2. Fahn, S. Ann. N. Y. Acad. Sci. 2003, 991, 1-14.
  3. Marsden, C. D. J. Neurol. Neurosurg. Psychiatry 1994, 57, 672-681. https://doi.org/10.1136/jnnp.57.6.672
  4. Jankovic, J. Mov. Disord. 2005, 20, S11-S16.
  5. Cheng, N.; Maeda, T.; Kume, T.; Kaneko, S.; Kochiyama, H.; Akaike, A.; Goshima, Y.; Misu, Y. Brain Res. 1996, 16, 278-283.
  6. Walkinshaw, G.; Waters, C. M. J. Clin. Invest. 1995, 95, 2458-2464. https://doi.org/10.1172/JCI117946
  7. Shin, K. S.; Zhao, T. T.; Park, K. H.; Park, H. J.; Hwang, B. Y.; Lee, C. K.; Lee, M. K. BMC Neurosci. 2015, 16, 23. https://doi.org/10.1186/s12868-015-0163-5
  8. Bove, J.; Perier, C. Neuroscience 2012, 211, 51-76. https://doi.org/10.1016/j.neuroscience.2011.10.057
  9. Jackson-Lewis, V.; Blesa, J.; Przedborski, S. Parkinsonism Relat. Disord. 2012, 18, S183-S185.
  10. Seidl, S. E.; Potashkin, J. A. Front. Neurol. 2011, 2, 68.
  11. Razmovski-Naumovski, V.; Huang, T. H. W.; Tran, V. H.; Li, G. Q.; Duke, C. C.; Roufogalis, B. D. Phytochem. Rev. 2005, 4, 197-219. https://doi.org/10.1007/s11101-005-3754-4
  12. Im, S. A.; Choi, H. S.; Hwang, B. Y.; Lee, M. K.; Lee C.K. Kor. J. Pharmacogn. 2009, 40, 35-40.
  13. Choi, H. S.; Zhao, T. T.; Shin, K. S.; Kim, S. H.; Hwang, B. Y.; Lee, C. K.; Lee, M. K. Molecules 2013, 18, 4342-4356. https://doi.org/10.3390/molecules18044342
  14. Choi, H. S.; Park, M. S.; Kim, S. H.; Hwang, B. Y.; Lee, C. K.; Lee, M. K. Molecules 2010, 15, 2814-2824. https://doi.org/10.3390/molecules15042814
  15. Shang, L. S.; Liu, J. C.; Zhu, Q. J.; Zhao, L.; Feng, Y.; Wang, X.; Cao, W.; Xin, H. Brain Res. 2006, 1102, 163-174. https://doi.org/10.1016/j.brainres.2006.05.035
  16. Wang, P.; Niu, L.; Guo, X. D.; Gao, L.; Li, W. X.; Jia, D.; Wang, X. L; Ma, L. T.; Gao, G. D. Brain Res. Bull. 2010, 83, 266-271. https://doi.org/10.1016/j.brainresbull.2010.06.014
  17. Zhang, G.; Zhao, Z.; Gao, L.; Deng, J.; Wang, B.; Xu, D.; Liu, B.; Qu, Y.; Yu, J.; Li, J.; Gao, G. Pharmacol. Biochem. Behav. 2011, 99, 42-51. https://doi.org/10.1016/j.pbb.2011.03.019
  18. Wang, P.; Niu, L.; Gao, L.; Li, W. X.; Jia, D.; Wang, X. L.; Gao G. D. J. Int. Med. Res. 2010, 38, 1084-1092. https://doi.org/10.1177/147323001003800336
  19. Paxinos, G.; Watson, C. The rat brain in stereotaxic coordinates 2nd ed: Academic Press; Australia, 1986.
  20. Schwarting, R. K. W.; Huston, J. P. Prog. Neurobiol. 1996, 50, 275-331. https://doi.org/10.1016/S0301-0082(96)00040-8
  21. Mo, J.; Zhang, H.; Yu, L. P.; Sun, P. H.; Jin, G. Z.; Zhen, X. Neurobiol. Aging 2010, 31, 926-936 https://doi.org/10.1016/j.neurobiolaging.2008.06.017
  22. Izurieta-Sanchez, P.; Sarre, S.; Ebinger, G.; Michotte, Y. Eur. J. Pharmacol. 1998, 353, 33-42. https://doi.org/10.1016/S0014-2999(98)00393-8
  23. Ljungberg, T.; Ungerstedt, U. Eur. J. Pharmacol. 1977, 46, 147-151. https://doi.org/10.1016/0014-2999(77)90250-3
  24. Blesa, J.; Phani, S.; Jackson-Lewis, V.; Przedborski, S. J. BioMed. Biotechnol. 2012, 2012, 845618.
  25. Shin, K. S.; Zhao, T. T.; Choi, H. S.; Hwang, B. Y.; Lee, C. K.; Lee, M. K. Brain Res. 2014, 1567, 57-65. https://doi.org/10.1016/j.brainres.2014.04.015
  26. Cenci, M. A. Parkinsonism Relat. Disord. 2007, 13, S263- S267. https://doi.org/10.1016/S1353-8020(08)70014-2
  27. Cohen, G. Neurotoxicology 1984, 5, 77-82.
  28. Soto-Otero, R.; Mendez-Alvarez, E.; Hermida-Ameijeiras, A.; Munoz-Patino, A. M.; Labandeira-Garcia, J. L. J. Neurochem. 2000, 74, 1605-1612.
  29. Cadet, J. L.; Brannock, C. Neurochem. Int. 1998, 32, 117-131. https://doi.org/10.1016/S0197-0186(97)00031-4
  30. Fahn, S.; Cohen, G. Ann. Neurol. 1992, 32, 804-812. https://doi.org/10.1002/ana.410320616
  31. Schober, A. Cell Tissue Res. 2004, 318, 215-224. https://doi.org/10.1007/s00441-004-0938-y
  32. Blandini, F.; Armentero, M. T.; Martignoni, E. Parkinsonism Relat. Disord. 2008, 14, S124-S129. https://doi.org/10.1016/j.parkreldis.2008.04.015
  33. Severson, J. A.; Marcusson, J.; Winblad, B.; Finch, C. E. J. Neurochem. 1982, 39, 1623-1631. https://doi.org/10.1111/j.1471-4159.1982.tb07996.x
  34. Linert, W.; Herlinger, E.; Jameson, R. F.; Kienzl, E.; Jellinger, K.; Youdim, M. B. Biochim. Biophys. Acta 1996, 1316, 160-168. https://doi.org/10.1016/0925-4439(96)00020-8
  35. Maharaj, H.; Sukhdev Maharaj, D.; Scheepers, M.; Mokokong, R.; Daya, S. Brain Res. 2005, 1063, 180-186. https://doi.org/10.1016/j.brainres.2005.09.041
  36. Basma, A. N.; Morris, E. J.; Nicklas, W. J.; Geller, H. M. J. Neurochem. 1995, 64, 825-832.
  37. Migheli, R.; Godani, C.; Sciola, L.; Delogu, M. R.; Serra, P. A.; Zangani, D.; De Natale, G.; Miele, E.; Desole, M. S. J. Neurochem. 1999, 73, 1155-1163.
  38. Zhang, L.; Dawson, V. L.; Dawson, T. M. Pharmacol. Ther. 2006, 109, 33-41. https://doi.org/10.1016/j.pharmthera.2005.05.007
  39. Padovan-Neto, F. E.; Echeverry, M. B.; Tumas, V.; Del-Bel, E. A. Neuroscience 2009, 159, 927-935. https://doi.org/10.1016/j.neuroscience.2009.01.034
  40. Nicklas, W. J.; Vyas, I.; Heikkila, R. E. Life Sci. 1985, 36, 2503-2508. https://doi.org/10.1016/0024-3205(85)90146-8
  41. Yacoubian, T. A.; Standaert, D. G. Biochim. Biophys. Acta 2009, 1792, 676-687. https://doi.org/10.1016/j.bbadis.2008.09.009
  42. Cai, T. S.; Zhang, S. F.; Wang M. C. Chin. J. Clin. Rehabil. 2005, 9, 106-107.
  43. Tanner, M. A.; Bu, X.; Steimle, J. A.; Myers, P. R. Nitric Oxide 1999, 3, 359-365. https://doi.org/10.1006/niox.1999.0245

Cited by

  1. Chemical Identification of Isoflavonoids from a Termite-Associated Streptomyces sp. RB1 and Their Neuroprotective Effects in Murine Hippocampal HT22 Cell Line vol.19, pp.9, 2016, https://doi.org/10.3390/ijms19092640