Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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The Inhibition of Epileptogenesis During Status Epilepticus by Ginsenosides of Korean Red Ginseng and Ginseng Cell Culture (Dan25)

  • N.E., Chepurnova (Biological Faculty of Lomonosov Moscow State University) ;
  • Park, Jin-Kyu (R&D Center Pharmaco design Co.) ;
  • O.M., Redkozubova (Biological Faculty of Lomonosov Moscow State University) ;
  • A.A., Pravdukhina (Biological Faculty of Lomonosov Moscow State University) ;
  • K.R., Abbasova (Biological Faculty of Lomonosov Moscow State University) ;
  • E.V., Buzinova (Biological Faculty of Lomonosov Moscow State University) ;
  • A.A., Mirina (Biological Faculty of Lomonosov Moscow State University) ;
  • D.A., Chepurnova (Biological Faculty of Lomonosov Moscow State University) ;
  • A.A., Dubina (Tomography & Spectroscopy Center of Lomonosov Moscow State University) ;
  • U.A., Pirogov (Tomography & Spectroscopy Center of Lomonosov Moscow State University) ;
  • M., De Curtis (Institute Neurology 'Carlo Besta') ;
  • L., Uva (Institute Neurology 'Carlo Besta') ;
  • S.A., Chepurnov (Tomography & Spectroscopy Center of Lomonosov Moscow State University)
  • Published : 2007.09.30
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Abstract

Pharmacology of Korean Red ginseng gives us unique possibility to develop new class of antiepileptic drugs today and to improve one's biological activity. The chemical structures of ginsenosides (GS) have some principal differences from well-known antiepileptic new generation drugs. The antiepileptic effect of GS was also demonstrated in all models of epilepsy in rats (young and adult), which have studied, in all models of epilepsy including status epilepticus (SE), induced by lithium - pilocarpine. In our experiments in rats new evidences on protective effects were exerted as a result of premedication by GS. Pre-treatment of several GS could induce decrease of the seizures severity and brain structural damage (by MRI), neuronal degeneration in hippocampus. Wave nature of severity of motor seizures during convulsive SE was observed during lithium-pilocarpine model of SE in rats (the first increase of seizures was 30 min after the beginning of SE and the second - 90 min after. The efficacy of treatment on SE by ginsenoside as expected was observed after no less 3 weeks by daily GS i.p. administration. It is blocked SE or significantly decrease the severity of seizures during SE. The implication of presented data is that combination of ginsenosides from Korean Red ginseng and ginseng cell culture Dan25 that could be applied for prevention of epileptical status development. However, a development of optimal ratio of different ginsenosides $(Rb_1$ Rc, Rg, Rf,) should consummate in the new antiepileptic drug development.

Keywords

References

  1. Chepurnov, S. A., Chepurnova, N. E. and Park, Jin-Kyu.: Ginseng could counteract aging, or brain disorders (As preventive medicine). In: 'The Korea Times'. Seoul. September 11, 3 (1994)
  2. Chepurnov, S. A., Chepurnova, N. E., Jin Kyu Park, Lubimov, I. I., Buzinova, E. V. and Kabanova, N. P.: Central effects of saponin components and polysaccarides fraction in Korean red ginseng. Proceedings of the 5th Life of Science Symposium on Biomedical research with Korean Red Ginseng. KGTRI, Korea. 83-108 (1994)
  3. Chepurnov, S. A., Chepurnova, N. E., Park Jin Kyu, Lubimov I. I., Buzinova E. V., Kabanova N. P. and Ki Yeul Nam.: The central effects of saponin components and polysaccarides fraction from Korean Red Ginseng. Korean Journal Ginseng Sci. 18, 165-174 (1994)
  4. Chepurnov, S. A., Chepurnova, N. E., Park, Jin Kyu, Buzinova, E. V., Sato, M., Borzenkov, V. M. and Lubimov, I. I.: Cognitive functions and epilepsy. - The improving influences of the triol ginseng saponins and neuropeptides. Symposium: 'The molecular and the cells genetic mechanisms of adaptive behavior'. Saint-Petersburg (1994)
  5. Chepurnova, N. E., Chepurnov, S. A., Park, Jin-Kyu and Nam, Ki-youl.: Febrile hyperthermia-induced seizures and perspectives of cognitive functions development (experimental study). Epilepsia. 36. Suppl. 3, S46 (1995)
  6. Chepurnov, S. A. and Chepurnova, N. E.: Epilepsy and Ginseng - modern Euro-Asian Art. The Int. Congress 'Epilepsy - A Developing World'. Chine, Beijing. April 22-28 (1996)
  7. Park, Jin-Kyu, Chepurnova, N. E., Abbasova, K. R. and Chepurnov, S. A.: The influence of ginsenosides of Korean Red Ginseng on the febrile hyperthermia-induced seizures in the rat: long term inpacts for development of the cognitive functions. In: Inaugural Congress of Asian & Oceanian Epilepsy Organization. '96 AOEO. September 6-7, 1996. Seoul, Korea 34 (1996)
  8. Chepurnov, S. A., Chepurnova, N. E., Park, Jin-Kyu, Abbasova, K. R. and Klueva, U. A.: Effects of seizures activity in neonatal period on the learning and relearning in adult rats. (The improving role of the giunsenosides). In: Inaugural Congress of Asian & Oceanian Epilepsy Organization. '96 AOEO. September 6-7, 1996. Seoul, Korea. Abstr. O-1-5, 16 (1996)
  9. Chepurnov, S. A. and Chepurnova, N. E.: Ginsenisides in epileptogenesis of the developing brain. The 1st Congress of Asian & Oceanian Epilepsy Organization. // '98 AOEO. October, 1998. Taiwan. Taibei. (1998)
  10. Chepurnov, S. A., Park, Jin Kyu, van Luijtelaar, E. L. J. M., Chepurnova, N. E., Strogov, S. E., Mikhaylova, O. M., et al.: Antiepileptical properties of ginsenozides from Korean Red Ginseng and ginseng cell cultures (dan25) In: The Plant Resources Societ.y of Korea. The 7th International Symposium. 'Proceding of Internatioonal Symposium for the Development of Medical Plants.' Cultural Center for Inje-Kun. Korea. October 27-29, 2000‚ a 116-122 (2000)
  11. Chepurnov, S. A., Park, Jin-Kyu, Chepurnova, N. E., et al.: Ginseng in the mechanisms of brain excitability regulation – The way for progress. Advances in Ginseng Research (Ed. Nam-In Baek). 84-95. (2002)
  12. Park, Jin-Kyu, Chepurnova, N. E. and Chepurnov, S. A.: Ginseng in treatment of epilepsy: 'Pro' and 'contra' of plant medicine. XVII Konferencia Naukowa na temat Padaczki Polskiego towarzystwa epileptologii. Lodz. 8-10 maja, 2003.//Epileptologia. Supl. 1, 11, 92-93 (2003)
  13. Chepurnov, S. A., Park, Jin-Kyu and Chepurnova, N. E.: Ginsenosides ($Rb_1,\;Rb_2$, Rc) in the mechanisms of antiepileptogenesis. XVII Konferencia Naukowa na temat Padaczki Polskiego towarzystwa epileptologii. Lodz. 8-10 maja, 2003. // Epileptologia. Supl. 1. 11, 91-92 (2003)
  14. Chepurnova, N. E., Park, Jin Kyu, Buzinova, E. U. and Chepurnov, S. A.: The ginsenosides in the mechanisms of memory and epileptogenesis. Russian. Physiological Journal named I.M.Sechenov. 90, Part 1. 286-187 (2004)
  15. Tsang, D., Yeung, H. W., Tso, W. W. and Peck, H.: Ginseng saponins: influence on neurotransmitter uptake in rat brain synaptosomes. Planta Medica, 3, 221-224 (1985)
  16. Kimura, P. A., Saunders, H. S. Kim, H. M. Rheu, K. W. Oh and Ho, I. K.: Interactions of ginsenosides with ligand-bindings of $GABA_A\;and\;GABA_B$ receptors, General Pharmacology: The Vascular System, 25(1), 193-199 (1994) https://doi.org/10.1016/0306-3623(94)90032-9
  17. Jeong, T. C., Kim, H. J., Park, J. I., Ha, C. S., Park, J. D., Kim, S. I. and Roh, J. K.: Protective effects of red ginseng saponins against carbon tetrachloride-induced hepatotoxicity in Sprague Dawley rats, Planta Medica, 63(2), 136-140 (1997) https://doi.org/10.1055/s-2006-957630
  18. Chang, Y. S. and Seo, E. K.: Gyllenhaal, Ch. Panax ginseng: A Role in Cancer Therapy. Integrative Cancer Therapies, 2, 13-33 (2003) https://doi.org/10.1177/1534735403251167
  19. Park, Jin Kyu, Namegung, Uk, Lee, Chang Long, Park, Jong Oh. Jin, Sung-Ha, Kwon, Oh Bin et al.: Calcium-independent CaMKII activity is involved in ginsenoside $Rb_1$-mediated neuronal recovery after hypoxic damage. Life Science 76, 1013-1025 (2005) https://doi.org/10.1016/j.lfs.2004.10.011
  20. Shen, L. and Zhang, J.: Ginsenoside $Rg_1$ increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils. Neuroscience Letters 344, 1-4 (2003) https://doi.org/10.1016/S0304-3940(03)00318-5
  21. Chepurnov, S. A., Chepurnova, N.E. and Redkozuova, O.M.: Status epilepticus – a new mrchnisms and way of inhibition (lithium-pilocarpine model). Uspekhi Physiologicheskih Nauk (in Russian), 36, 68-83 (2005)
  22. Houser, C. R. and Esclapez, M.: Down regulation of the alpha5 subunit of the GABA(A) receptor in the pilocarpine model of temporal lobe epilepsy. Hippocampus. 13, 633-645 (2003) https://doi.org/10.1002/hipo.10108
  23. Lowenstein, D. H. and Alldredge, B. K.: Status epilepticus. N. Engl. J. Med., 338, 970-976 (1998) https://doi.org/10.1056/NEJM199804023381407
  24. Status epilepticus. Mechanisms and management. Eds.: Wasterline C., Teiman D.M. The MIT Press, (2006)
  25. Turski, W. A.: Pilocarpine-induced seizures in rodents -17 years on, Polish Journal of Pharmacology, 52, 63-65 (2000)
  26. Cavalheiro, E.A.: The pilocarpine model of epilepsy Italian Journal of Neurological Sciences, 16, 33-37 (1995) https://doi.org/10.1007/BF02229072
  27. Chaudhary, G. and Gupta, Y. K.: Lithium does not synergize the peripheral action of cholinomimetics as seen in the central nervous system. Life Sciense, 68, 2115-2121 (2001) https://doi.org/10.1016/S0024-3205(01)00994-8
  28. Cavalheiro, E. A., Leite, J. P., Bortolotto, Z. A., Turski, W. A., Ikonomidou, C. and Turski, L.: Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32, 778-782 (1995) https://doi.org/10.1111/j.1528-1157.1991.tb05533.x
  29. Avanzini, G. and Farello R.: Animal model of epilepsies. In: Molecular and cellular targets for anti-epileptic drugs. Eds.: G. Avanzini, Regesta G. et al., John Libbey. London (2000)
  30. Berkely, J. L., Decker, M. J. and Levey, A. I.: The role of muscarinic acetylcholine receptor-mediated activation of extracellular signal-regulated kinase1/2 in pilocarpine-induced seizures//Journ. of Neurochenistry, 82, 192-201 (2002) https://doi.org/10.1046/j.1471-4159.2002.00977.x
  31. Jones, D. M., Esmaeil, N., Maren, S. and MacDonald, R. L.: Characterization of pharmacoresistance to benzodiazepines in the rat Li-pilocarpine model of status epilepticus. Epilepsy Res., 50, 301-312 (2002) https://doi.org/10.1016/S0920-1211(02)00085-2
  32. Honchar, M. P., Olney, J. W. and Sherman, W. R.: Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats. Science, 220(4594), 323-325 (1983) https://doi.org/10.1126/science.6301005
  33. Van Camp, N., D'Hoog, R., Derhoye, M. and Peeters, R. R.: Smultaneous EEG recordingggg and functional magnetic resonance imaging during pentylenetetrazol-induced seizures in rat. Neurimage, 19, 627-636 (2003) https://doi.org/10.1016/S1053-8119(03)00138-1
  34. Konstantinova, N. F., Makhankov, V. V., Uvareova, N. I., Samoshina, N. F., Sova, V. V. and Michailova O. M.: Study on the dynamic of biosynthesis of ginsenozides the growth cycle cell culture of ginseng. Biotekhnolobgia, 9-10, 35-39 (1995)
  35. Kondratyev, A. and Gale, K.: Latency to onset of status epilepticus determines molecular mechanisms of seizure-induced cell death. Molecular Brain Research, 121, 86-94 (2004) https://doi.org/10.1016/j.molbrainres.2003.11.005
  36. Niimura, M., Moussa, R., Bisson. N. and Ikeda-Duglas, C. et al.: Changes phosphorilation of the NMDA receptor in the rat hippocampus induced by status epilepticus. Journ. Neurochemistry 92, 1377-1385(2005) https://doi.org/10.1111/j.1471-4159.2005.02977.x
  37. Chepurnova, N. E., De Curtis, Uva, L., Chepurov, S. A., Redkozubova, O. M. and Gonchaov, O. B.: Status epilepticus in rat and Guinea pig (lithium-pilocarpine and PTZ models)//Epilepsia, 46, Spl. 6, 364 (2005)
  38. Shuler, P., Hentshel, D., Stefan, H. and Huk, W.: Quantitive magnetic resonance imaging (qMRI) and spectroscopy (qMRS) in epilepsies. : In: 'Focus localization'. Eds.: G. Pawlik, H.Stefan. Koln,Germany, 79-94 (2000)
  39. Roch, C., Leroy, Cl., Nehlig, A. and Namer, I.: magnetic resonnce imaging in te study of the lithium-pilocarpine model of temporal lobe epilepsy in adult rats. Epi;lepsia 43(4), 325-335, (2002) https://doi.org/10.1046/j.1528-1157.2002.11301.x
  40. Spinella, M.: Herbal medicines and epilepsy. The potential for benefit and adverse effects. Epilepsy & Behavior, 2, 524-532 (2001) https://doi.org/10.1006/ebeh.2001.0281
  41. Finn, Z. and Lennart, D.: Phytotherapy. Experimental and clinichen ginseng trials. www.nycomed.ru
  42. Tanaka, O. and Kasai, R.: Saponins of ginseng and related plants. Progress in the Chemistry of Organic Natural Products, 46, 1-42 (1984)
  43. Vogler, B. K., Pittler, M. H. and Ernst, E.: The efficacy of ginseng: a systematic review of randomised clinical trials. Eur J Clin Pharmacol., 55, 567–575 (1999)
  44. Lian, X. Y., Zhang, Z. Z. and Stringer, J. L.: Anticonvulsant activity of ginseng on seizures induced by chemical convulsants. Epilepsia; 46(1), 15-22 (2005)
  45. Park, J.-K., Jin, S.-H., Choi, K.-H., Ko, J.-H. and Nam, K.-Y.: Influence of ginsenosides on the kainik acid –indiced seizure activity in immaturerats : Journ. Biochem. Molec. Biol., 32, 339-344 (1999)
  46. Park, J.-K., Jin, S.-H., Choi, K.-H., Ko, J.-H. et al.: Effect of herbal preparation containing ginsend on learning and memory in kainite-indiced seizures In : Proceed of Intern Symp for the development of medical plants. Korea, Inje Kun, 2000 The Plant resource Society of Korea &th Inern Symposium 84-95 (2000)
  47. Lee, J.-H., Kim, S.-R., Bae, C.-S., Kim, D., Hong, H.-N. and Nah, S-Y.: Protective effect of ginsenosides, active ingredients of Panax ginseng, on kainic acid-induced neurotoxicity in rat hippocampus. Neuroscience Letters, 325, 129-133. (2002) https://doi.org/10.1016/S0304-3940(02)00256-2
  48. Lee, J. K., Choi, S. S., Lee, H. K. et al.: Effects of ginsenosides Rd and decursinol on the neurotoxic responces induced by kainic acid in mice. Planta Med., 69, 230-234 (2003) https://doi.org/10.1055/s-2003-38475
  49. Majores, M., Eils, J., Wiestler, O. D. and Becker, A. J.: Molecular profiling of temporal lobe epilepsy: comparison of data from human tissue samples andanimal models. Epilepsy Research (2004)
  50. Kim, H. S., Kim, K. S. and Oh, K. W.: Inhibition by ginsenosides $Rb_1\;and\;Rg_1$ of cocaine- induced hyperactivity conditionedplace preference, and postsynaptic dopamine receptor supersensitivity in mice. Pharmacol. Biochem. Behav., 63, 407-412 (1999) https://doi.org/10.1016/S0091-3057(99)00020-9
  51. Tachikawa, E., Kudo, K., Harada, K., Kashimoto, T., Miyate, Y., Kakizaki, A. and Takahashi, E.: Effects of ginseng saponins on responses induced by various receptor stimuli. European Journ. Pharmacol., 369, 23-32 (1999) https://doi.org/10.1016/S0014-2999(99)00043-6
  52. Choi, S. E., Choi, S., Lee, J. H., Whiting, P. J., Lee, S. M. and Nah, S. Y.: Effects of ginsenosides on GABA(A) receptor channels expressed in Xenopus oocytes. Archives of Pharmacol. Res., 26, 28-33 (2003) https://doi.org/10.1007/BF03179927
  53. Kim, H. S., Lee, J. H., Goo, Y. S. and Nah, S. Y.: Effects of ginsenosides on Ca+2 Channels and membrane capacitance in rat adrenal chromaffin cells. Brain Research Bulletin, 46, 245-251 (1998) https://doi.org/10.1016/S0361-9230(98)00014-8
  54. Mook-Jung, I., Hong, H. S., Boo, J. H., Lee, K. H., Yun, S. H., Cheong, M. Y., Joo, I., Huh, K. and Jung, M. W.: Ginsenoside $Rb_1\;and\;Rg_1$ improve spatial learning and increase hippocampal synaptophysin level in mice. Journ. Neurosci. Res., 63, 509-615 (2001) https://doi.org/10.1002/jnr.1045
  55. Lim, J. H., Wen, T. C., Matsuda, S., Tanaka, J., Maeda, N., Peng, H., Aburaya, J., Ishihara, K., and Sakanaka, M.: Protection of ischemic hippocampal neurons by ginsenoside $Rb_1$, a main ingredient of ginseng root. Neuroscience Research, 28, 191-200 (1997) https://doi.org/10.1016/S0168-0102(97)00041-2
  56. Wen, T. C., Yoshimura, H., Matsuda, S., Lim, J. H. and Sakanaka, M.: Ginseng root prevents learning disability and neuronal loss in gerbils with 5-minute forebrain ischemia. Acta Neuropathology, 91, 15-22 (1996) https://doi.org/10.1007/s004010050387
  57. Benishin, C. G., Lee, R., Wang, L. C. and Liu, H. J.: Effects of ginsenoside $Rb_1$ on central cholinergic metabolism. Pharmacology, 42, 223-229 (1991) https://doi.org/10.1159/000138801
  58. Smolders, I., Khan, G. M., Manil, J., Ebinger, G. and Michotte, Y.: NMDA receptor-mediated pilocarpine-induced seizures: Characterization in freely moving rats by microdialysis, British Journ. Pharmacol., 121(6), 1171-1179 (1997) https://doi.org/10.1038/sj.bjp.0701231
  59. Kim, S., Ahn, K., Oh, T. H., Nah, S. Y. and Rhim, H.: Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem. Biophysic. Research Commun., 296, 247-254 (2002) https://doi.org/10.1016/S0006-291X(02)00870-7
  60. Kim, S. and Rhim, H.: Ginsenosides inhibit NMDA receptor-mediated epileptic discharges in cultured hippocampal neurons. Arch. Pharm. Res., 27(5), 524-530 (2004) https://doi.org/10.1007/BF02980126
  61. Shen, L. and Zhang, J.: Ginsenoside $Rg_1$ increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils. Neuroscience Letters, 344, 1-4 (2003) https://doi.org/10.1016/S0304-3940(03)00318-5
  62. Liao, B., Newmark, H. and Zhou, R.: Neuroprotective effects of ginseng total saponin and ginsenosides $Rb_1\;and\;Rg_1$ on spinal cord neurons in vitro. Experimental Neurology., 173, 224-234 (2002) https://doi.org/10.1006/exnr.2001.7841
  63. Salim, K. N., McEwen, B. S. and Chao, H. M.: Ginsenoside $Rb_1$ regulates ChAT, NGF and trkA mRNA expression in the rat brain. Molecular Brain Research, 47, 177-182 (1997) https://doi.org/10.1016/S0169-328X(97)00042-9
  64. Lee, S. H., Yand, S. C., Park, J. K., Jung, M. W. and Lee, C.J.: Reduction ofelectrical evoked neural; activity by ginseng saponin in rat hippocampal slices. Biol. And Pharmacol. Bulletin 173, 224-234 (2000)
  65. Lee, Jum-Ho, Jeong, Sang Mi, Kim, Jong-Hoon, Lee, Byung-Hwan et al.: Characteristics of ginsenoside $Rg_3$-mediated brain Na+ current inhibition. Molec. Parmocology. 68, 1114-1126 (2005) https://doi.org/10.1124/mol.105.015115
  66. Li, J. and Zhang, J.: Inhibition of apoptosis by ginsenoside $Rg_1$ in cultured cortical neurons. Chin. Med J, 110(7), 535-539 (1997)
  67. Young, C. Kim, So, R. Kim, George J. Ma, rkelonis, and Tae, H. Oh.: Ginsenosides $Rg_1\;and\;Rg_3$ protect cultured rat cortical cells from glutamate-induced neurodegeneration, Journal of Neuroscience Research, 53, 426-432 (1998) https://doi.org/10.1002/(SICI)1097-4547(19980815)53:4<426::AID-JNR4>3.0.CO;2-8
  68. Hiai, S., Yokoyama, H., Oura, H. and Yano, S.: Stimulation of pituitary– adrenocortical system by ginseng saponin. Endocrinol. Jpn., 26, 661-665 (1979) https://doi.org/10.1507/endocrj1954.26.661
  69. Lee, Y. J., Chung, E., Lee, K. Y., Lee, Y. H., Huh, B. and Lee, S. K.: Ginsenoside- $Rg_1$, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor. Mol. Cell. Endocrinol., 133, 135-140 (1997) https://doi.org/10.1016/S0303-7207(97)00160-3