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Perspectives for Ginsenosides in Models of Parkinson's Disease

  • Published : 2007.09.30

Abstract

Ginseng, the root of Panax species, is a well-known herbal medicine. It has been used as traditional medicine in Korea, China and Japan for thousands of years and now is a popular and worldwide natural medicine. The active principles of ginseng are ginsenosides which are also called ginseng saponins. Traditionally ginseng has been used primarily as a tonic to invigorate weak body functions and help the restoration of homeostasis. Current in vivo and in vitro studies demonstrate its beneficial effects in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Moreover, recent research indicates that some of ginseng's active ingredients exert beneficial actions on aging and neurodegenerative disorders such as Parkinson´s disease. Essentially, antioxidant, antiinflammatory, anti-apoptotic and immunostimulant activities are mostly underlying the postulated ginseng-mediated protective mechanisms. Next to animal studies, data from neural cell cultures contribute to the understanding of these mechanisms which involve decreasing nitric oxide, scavenging of free radicals and counteracting excitotoxicity. This paper focuses on own and other neuroprotective data on ginseng for dopaminergic neurons and intends to show aspects where neuroprotection e.g. by ginsenosides, additionally or preceding standard Parkinson therapy, could come about as a valuable contribution to slow neurodegenerative processes.

Keywords

References

  1. Paulus, W. and Jellinger, K.: The neuropathologic basis of different clinical subgroups of Parkinson's disease. J. Neuropathol. Exp. Neurol. 50, 743-755. (1991) https://doi.org/10.1097/00005072-199111000-00006
  2. Yuan, H., Sarre, S., Ebinger, G. and Michotte, Y.: Neuroprotective and neurotrophic effect of apomorphine in the striatal 6-OHDA-lesion rat model of Parkinson's disease. Brain Res. 1026, 95-107 (2004) https://doi.org/10.1016/j.brainres.2004.08.015
  3. Jenner, P., Schapira, A. H. and Marsden, C. D.: New insights into the cause of Parkinson's disease. Neurology 42, 2241-2250 (1992) https://doi.org/10.1212/WNL.42.12.2241
  4. Olanow, C. W.: A radical hypothesis for neurodegeneration. Trends Neurosci. 16, 439-444 (1993) https://doi.org/10.1016/0166-2236(93)90070-3
  5. Birkmayer, W. and Hornykiewicz, O.: The effect of l-3,4-dihydroxyphenylalanine (= DOPA) on akinesia in parkinsonism.. Wien. Klin. Wochenschr. 113, 851-854 (1961)
  6. Chase, T. N., Mouradian, M. M. and Engber, T. M.: Motor response complications and the function of striatal efferent systems. Neurology 4, 23-27 (1993)
  7. Nutt, J. G.: Clinical pharmacology of levodopa-induced dyskinesia. Ann. Neurol. 47, 160-164 (2000)
  8. Metman, L. V., Konitsiotis, S. and Chase, T. N.: Pathophysiology of motor response complications in Parkinson's disease: hypotheses on the why, where, and what. Mov. Disord. 15, 3-8 (2000) https://doi.org/10.1002/1531-8257(200001)15:1<3::AID-MDS1003>3.0.CO;2-E
  9. Ling, Z. D., Pieri, S. C. and Carvey, P. M.: Comparison of the neurotoxicity of dihydroxyphenylalanine stereoisomers in cultured dopamine neurons. Clin. Neuropharmacol. 19, 360-365 (1996) https://doi.org/10.1097/00002826-199619040-00010
  10. Mytilineou, C., Han, S. K. and Cohen, G.: Toxic and protective effects of L-dopa on mesencephalic cell cultures. J. Neurochem. 61, 1470-1478 (1993) https://doi.org/10.1111/j.1471-4159.1993.tb13642.x
  11. Hefti, F., Melamed, E., Bhawan, J. and Wurtman, R.: Long-term administration of L.dopa does not damage dopaminergic neurons in the mouse. Neurology 31, 1194-1195 (1981) https://doi.org/10.1212/WNL.31.9.1194
  12. Perry, T. L., Yong, V. W., Ito, M., Foulks, J. G., Wall, R. A., Godin, D. V. and Clavier, R. M.: Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of L-DOPA and carbidopa chronically. J. Neurochem. 43, 990-993 (1984) https://doi.org/10.1111/j.1471-4159.1984.tb12834.x
  13. Quinn, N., Parkes, D., Janota, I. and Marsden, C. D.: Preservation of the substantia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four-year period. Mov. Disord. 1, 65-68. (1986) https://doi.org/10.1002/mds.870010109
  14. Zigmond, M. J., Hastings, T. G. and Perez, R. G.: Increased dopamine turnover after partial loss of dopaminergic neurons: compensation or toxicity? Parkinsonism Rel. Disord. 8, 389-393 (2002) https://doi.org/10.1016/S1353-8020(02)00019-6
  15. Dziewczapolski, G., Murer, G., Agid Y., Gershanik, O. and Raisman-Vozari, R.: Absence of neurotoxicity of chronic L-DOPA in 6-hydroxydopamine-lesioned rats. Neuroreport 8, 975-979 (1997) https://doi.org/10.1097/00001756-199703030-00031
  16. Murer, M. G., Dziewczapolski, G., Menalled, L. B., Garcia, M. C., Agid, Y., Gershanik, O. and Raisman-Vozari, R.: Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions. Ann. Neurol. 43, 561-575 (1998) https://doi.org/10.1002/ana.410430504
  17. Ferrario, J. E., Delfino, M. A., Stefano, A. V., Zbarsky, V., Douhou, A., Murer, M. G., Raisman-Vozari, R. and Gershanik, O. S.: Effects of orally administered levodopa on mesencephalic dopaminergic neurons undergoing a degenerative process. Neurosc.i Res. 47, 431-436 (2003) https://doi.org/10.1016/j.neures.2003.08.001
  18. Spina, M. B. and Cohen, G.: Exposure of striatal synaptosomes to L-dopa increases levels of oxidized glutathione. J. Pharmacol. Exp. Ther. 247, 502-507 (1988)
  19. Fahn, S. and Cohen, G.: the oxidant stress hypothesis in Parkinson's disease: Evidence supporting it. Ann. Neurol. 32, 804-812 (1992) https://doi.org/10.1002/ana.410320616
  20. Lai, C. T. and Yu, P. H.: Dopamine- and L-beta-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced ctoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells: Effects of oxidative stress and antioxidative factors. Biochem. Pharmacol. 53, 363-372 (1997) https://doi.org/10.1016/S0006-2952(96)00731-9
  21. Pardo, B., Mena, M. A. and de Yebenes, J. G.: L-dopa inhibits complex IV of the electron transport chain in catecholamine-rich human neuroblastoma NB69 cells. J. Neurochem. 64, 576-582 (1995) https://doi.org/10.1046/j.1471-4159.1995.64020576.x
  22. Pedros, R. and Soares-da-Silva, P.: Oxidative and non-oxidative mechanisms of neuronal cell death and apoptosis by L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine. Br. J. Pharmacol. 137, 1305-1313 (2002) https://doi.org/10.1038/sj.bjp.0704982
  23. Muriel, M. P., Bernard, V., Levey, A. I., Laribi, O., Abrous, D. N., Agid, Y., Bloch, B. and Hirsch, E. C.: Levodopa induces a cytoplasmic localization of D1 dopamine receptors in striatal neurons in Parkinson's disease. Ann. Neurol. 46, 103-111 (1999) https://doi.org/10.1002/1531-8249(199907)46:1<103::AID-ANA15>3.0.CO;2-Z
  24. Muriel, M. P., Orieux, G. and Hirsch, E. C.: Levodopa but not ropinirole induces and internalization of D1 dopamine receptors in parkinsonian rats. Mov. Disord. 17, 1174-1179 (2002) https://doi.org/10.1002/mds.10256
  25. Kebabian, J. W. and Calne, D. B.: Multiple receptors for dopamine. Nature 277, 93-96 (1979) https://doi.org/10.1038/277093a0
  26. Missale, C., Nash, S. R., Robinson, S. W., Jaber, M. and Caron, M. G.: Dopamine receptors: from structure to function. Physiol. Rev. 78, 189-225 (1998) https://doi.org/10.1152/physrev.1998.78.1.189
  27. Sokoloff, P. and Schwartz, J. C.: Novel dopamine receptors half a decade later. Trends Pharmacol. Sci. 16, 270-275 (1995) https://doi.org/10.1016/S0165-6147(00)89044-6
  28. Foley, P., Gerlach, M., Double, K. L. and Riederer, P.: Dopamine receptor agonists in the therapy of Parkinson's disease. J. Neural Transm. 111, 1375-1446 (2004) https://doi.org/10.1007/s00702-003-0059-x
  29. Jenner, P.: Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease. Curr. Opin. Neurol. 16, 3-7 (2003)
  30. Reichmann, H.: Long-term treatment with dopamine agonists in idiopathic Parkinson's disease. J. Neurol. 247 [Suppl 4], 17-19 (2000) https://doi.org/10.1007/BF03161151
  31. Gille, G., Rausch, W. D., Hung, S. T., Moldzio, R., Janetzky, B., Hundemer, H. P., Kolter, T. and Reichmann, H.: Pergolide protects dopaminergic neurons in primary culture under stress conditions. J. Neural Transm. 109, 633-643 (2002) https://doi.org/10.1007/s007020200052
  32. Bonuccelli, U.: Comparing dopamine agonists in Parkinson's disease. Curr. Opin. Neurol. 16, 13-19 (2003) https://doi.org/10.1097/00019052-200312001-00004
  33. Gerlach, M., Double, K., Arzberger, T., Leblhuber, F., Tatschner, T. and Riederer, P.: Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J. Neural Transm. 110, 1119-1127 (2003) https://doi.org/10.1007/s00702-003-0027-5
  34. Le, W. D. and Jankovic, J.: Are dopamine receptor agonists neuroprotective in Parkinson's disease? Drugs Ageing 18, 389-296 (2001) https://doi.org/10.2165/00002512-200118060-00001
  35. Pirtosek, Z. and Flisar, D.: Neuroprotection and dopamine agonists. Adv. Exp. Med. Biol. 541, 55-74 (2004)
  36. Noverino, E., Amato, M. and Izzo, A. A.: The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia 71: 1-5 (2000) https://doi.org/10.1016/S0367-326X(99)00105-7
  37. Yun, T. K.: Brief introduction of Panax ginseng C.A. Meyer. J. Korean Med. Sci. 16: 53-55 (2001)
  38. Rhim, H., Kim, H., Lee, D. Y., Oh, T. H. and Nah, S. Y.: Ginseng and ginsenoside Rg3, a newly identical active ingredient of ginseng, modulate $Ca^{2+}$ channel currents in rat sensory neurons. Eur. J. Pharmacol. 463, 151-158 (2002)
  39. 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 ischaemia. Acta Neuropathol. 91, 15-22 (1996) https://doi.org/10.1007/s004010050387
  40. Tachikawa, E., Kudo, K., Harada, K., Kashimoto, T., Miyate, M. and Kakizaki, A.: Effects of ginseng saponins on responses induced by various receptor stimuli. Eur. J. Pharmacol. 369, 23-32. (1999) https://doi.org/10.1016/S0014-2999(99)00043-6
  41. Blumenthal, M.: Asian ginseng: potential therapeutic uses. Adv. Nurse Pract. 2, 26-28 (2001)
  42. Chu, G. X. and Chen, X.: Anti-lipid peroxidation and protection of ginsenosides against cerebral ischemia-reperfusion in rats. Zhongguo Yao Li Xue Bao 11, 119-123 (1990)
  43. Tyler, V. E.: The Honest Herbal-A Sensible Guide to the Use of Herbs and Related Remedies. Third ed. The Haworth Press, New York (1993)
  44. O'Hara, M., Kiefer, D., Farrell, K. and Kemper K.: A review of 12 commonly used medicinal herbs. Arch Fam Med 7, 523-536 (1998) https://doi.org/10.1001/archfami.7.6.523
  45. Sugaya, A., Yuzurihara, M., Tsuda, T., Yasuda, K., Kajiwara, K. and Sugaya, A. E.: Proliferative effect of ginseng saponin on neurite extension of primary cultured neurons of the rat cerebral cortex. J. Ethnopharmacol. 22,173-181(1988) https://doi.org/10.1016/0378-8741(88)90125-0
  46. Himi, T., Saito, H. and Nishiyama, N.: Effects of ginseng saponins on the survival of cerebral cortex neurons in cell cultures. Chem. Pharm. Bull. (Tokyo) 37, 481-484 (1989) https://doi.org/10.1248/cpb.37.481
  47. Mizumaki, Y., Kurimoto, M., Hirashima, Y., Nishijima, M., Kamiyama, H., Nagai, S., Takaku, A., Sugihara, K., Shimizu, M. and Endo, S.: Lipophilic fraction of Panax ginseng induces neuronal differentiation of PC12 cells and promotes neuronal survival of rat cortical neurons by protein kinase C dependent manner. Brain Res. 20, 254-260 (2002)
  48. Kim, Y. C., Kim, S. R., Markelonis, G. J. and Oh, T. H.: Ginsenosides $Rb_1\;and\;Rg_3$ protect cultured rat cortical cells from glutamate-induced neurodegeneration. J. Neurosci. Res. 4, 426-432 (1998)
  49. 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 ischaemia. Acta Neuropathol. 91, 15-22 (1996) https://doi.org/10.1007/s004010050387
  50. Lim, J. H., Wen, T. C., Matsuda, S., Tanaka, J., Maeda, N., Peng, H., Aburaya, J., Ishihara, K. and Sakanaka, M.: Protection of ischaemic hippocampal neurons by ginsenosides $Rb_1$, a main ingredient of ginseng root. Neurosci. Res. 28, 191-200 (1997) https://doi.org/10.1016/S0168-0102(97)00041-2
  51. Liu, C. X. and Xiao, P. G.: Recent advances on ginseng research in China. J. Ethnopharmacol. 36, 27-38 (1992) https://doi.org/10.1016/0378-8741(92)90057-X
  52. Van Kampen, J., Robertson, H., Hagg, T. and Drobitch, R.: Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease. Exp. Neurol. 184, 21-29 (2003)
  53. Radad, K., Gille, G. Moldzio R., Saito, H, Ishige K. and Rausch, W. D.: Ginsenosides $Rb_1\;and\;Rg_1$ effects on survival and neurite growth of $MPP^+$ -affected mesencephalic cells. J. Neural Transm. 111, 37-45 (2004) https://doi.org/10.1007/s00702-003-0063-1
  54. Tsang, D., Yeung, H. W., Tso, W. W. and Peck, H.: Ginseng saponins: influence on neurotransmitter uptake in rat brain synaptosomes. Planta Med. 3, 221-224 (1985)
  55. Chun, C. X., Gui, Z. Y., An, Z. L., Chun, H., Ying, C., Min, C. L., Fang, F., Can, Z. Y. and Hui, Z. C.: Ginsenoside $Rg_1$ attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress. Eur. J. Pharmacol. 473, 1-7 (2003) https://doi.org/10.1016/S0014-2999(03)01945-9
  56. Kim, E. H., Jang, M. H., Shin, M. C., Shin, M. S. and Kim, C. J.: Protective effect of aqueous extract of Ginseng radix against 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 cells. Biol. Pharm. Bull. 26, 1668-1673 (2003) https://doi.org/10.1248/bpb.26.1668
  57. Chen, X. C., Chen, Y., Zhu, Y. G., Fang, F. and Chen, L. M.: Protective effect of ginsenoside $Rg_1$ against MPTP-induced apoptosis in mouse substantia nigra neurons. Acta Pharmacol. Sin. 23, 829-834 (2002)
  58. Salim, K. N., McEven, B. S. and Choa, H. M.: Ginsenoside $Rg_1$ regulates ChAT, NGF and trkA mRNA expression in the rat brain. Brain Res. Mol. Brain Res. 47, 177-182 (1997) https://doi.org/10.1016/S0169-328X(97)00042-9
  59. Rudakewich, M., Ba, F. and Benishin, C. G.: Neurotrophic and neuroprotective actions of ginsenosides $Rb_1$ and $Rg_1$. Planta Med . 67, 533-537 (2001) https://doi.org/10.1055/s-2001-16488
  60. Kim, H. S., Zhang, Y. H., Fang, L. H. and Lee, M. K.: Effects of ginsenosides on bovine adrenal tyrosine hydroxylase. J. Ethnopharmacol. 66, 107-111 (1999) https://doi.org/10.1016/S0378-8741(98)00238-4
  61. Bliss, T. V. and Collingridge, G. L.: A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31-39 (1993) https://doi.org/10.1038/361031a0
  62. Malenka, R. C. and Nicoll R. A.: NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanism. Trends Neurosci. 16, 521-527 (1993) https://doi.org/10.1016/0166-2236(93)90197-T
  63. Plaitakis, A. and Shashidharan, P.: Glutamate transport and metabolism in dopaminergic neurons of substantia nigra: implications for the pathogenesis of Parkinson's disease. J. Neurol. 247. 1125-1135 (2000)
  64. Lipton, S. A. and Rosenberg, P. A.: Excitatory amino acids as a final common pathway for neurologic disorders. Engl. J. Med. 330, 613-622 (1994) https://doi.org/10.1056/NEJM199403033300907
  65. Sattler, R. and Tymiansky, M.: Molecular mechanism of calcium dependent excitotoxicity, J. Mol. Med. 78, 3-13 (2000) https://doi.org/10.1007/s001090000077
  66. Said, S. I., Pakbaz, H., Berisha, H. I. and Raza, S.: NMDA receptor activation: critical role in oxidant tissue injury. Free Radic. Bio. Med. 28, 1300-1302 (2000) https://doi.org/10.1016/S0891-5849(00)00289-6
  67. Doble, A.: The role of excitotoxicity in neurodegenerative disese: implication for therapy. Pharmacol. Ther. 81, 163-221 (1999) https://doi.org/10.1016/S0163-7258(98)00042-4
  68. Albin, R. L. and Greenamyre, J. T.: Alternative excitotoxic hypotheses. Neurology 42, 733-738 (1992) https://doi.org/10.1212/WNL.42.4.733
  69. Mizuno, Y., Ohta, S., Tanaka, M., Takamiya, S., Suzuki, K., Sato, T., Oya, H., Ozawa, T. and Kagawa, Y.: Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem. Biophys. Res. Commun. 163, 1450-1455 (1989) https://doi.org/10.1016/0006-291X(89)91141-8
  70. Rodriguez, M. C., Obeso, J. A. and Olanow, C. W.: Subthalamic nucleus mediated excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann. Neurol. 44, 175-188 (1998) https://doi.org/10.1002/ana.410440726
  71. Radad, K., Gille, G., Moldzio, R., Saito, H. and Rausch, W. D.: Ginsenosides $Rb_1$ and $Rg_1$ effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res. 1021, 41-53 (2004) https://doi.org/10.1016/j.brainres.2004.06.030
  72. Benishin, C. G.: Actions of ginsenoside $Rb_1$ on choline uptake in central cholinergic nerve endings. Neurochem. Int. 21, 1-5 (1992) https://doi.org/10.1016/0197-0186(92)90061-U
  73. Itoh, T., Zang, Y. F., Murai, S. and Saito, H.: Effects of Panax ginseng root on the vertical and horizontal motor activities and on brain monoamine-related substances in mice. Planta Med. 55, 429-433 (1989) https://doi.org/10.1055/s-2006-962058
  74. D'Angelo, L., Grimaldi, R., Caravaggi, M., Marcoli, M., Perucca, E., Lecchini, S., Frigo, G.M. and Crema, A.: A double-blind, placebo-controlled clinical study on the effect of a standardized ginseng extract on psychomotor performance in healthy volunteers. J. Ethnopharmacol. 16, 15-22 (1986) https://doi.org/10.1016/0378-8741(86)90063-2
  75. Kim, H. S., Kang, J. G., Seong, Y. H., Nam, K. Y. and Oh, K. W.: Blockade by ginseng total saponins of the development of cocaine induced reverse tolerance and dopamine receptor supersensitivity in mice. Pharmacol. Biochem. Behav. 50, 23-27 (1995) https://doi.org/10.1016/0091-3057(94)00224-7
  76. Kim, H. S., Kang, J. G. and Oh, K. W.: Inhibition by ginseng total saponins of the development of morphine reverse tolerance and dopamine receptor supersensitivity in mice. Gen. Pharmacol. 26,1071-1076 (1995) https://doi.org/10.1016/0306-3623(94)00267-Q
  77. Kim, H. S., Kang, J. G., Seong, Y. H., Nam, K. Y. and Oh, K. W.: Blockade by ginseng total saponins of the development of cocaine induced reverse tolerance and dopamine receptor supersensitivity in mice. Pharmacol. Biochem. Behav. 50, 23-27 (1995) https://doi.org/10.1016/0091-3057(94)00224-7
  78. Kim, H. S., Hong, Y. T., Oh, K. W., Seong, Y. H., Rheu, H. M. and Cho, D. H.: Inhibition by ginsenosides $Rb_1$ and $Rg_1$ of methamphetamine-induced hypersensitivity, conditioned place preference and post-synaptic dopamine receptor supersensitivity on mice. Gen. Pharmacol. 30, 783-789 (1998) https://doi.org/10.1016/S0306-3623(97)00330-3
  79. Shim, I., Won, J., Song, J., Kim, S. E. and Huh, S.: Modulatory effect of ginseng total saponins on dopamine release and tyrosine hydroxylase gene expression induced by nicotine in the mouse. J. Ethnopharmacol. 70, 161-169 (2000) https://doi.org/10.1016/S0378-8741(99)00166-X
  80. Petkov, V.: Effect of ginseng on the brain biogenic monoamines and 3',5'-AMP system. Experiments on rats. Arzneimittelforschung 28, 388-393 (1978)
  81. Wang, A., Cao, Y., Wang, Y., Zhao, R. and Liu, C.: Effects of Chinese ginseng root and stem-leaf saponins on learning, memory and biogenic monoamines of brain in rats. Zhongguo Zhong Yao Za Zhi 20, 493-495 (1995)
  82. Sala, F., Mulet, J., Choi, S., Jung, S. Y., Nah, S. Y., Rhim, H., Valor, L. M., Criado, M. and Sala, S.: Effects of ginsenoside $Rg_2$ on human neuronal nicotinic acetylcholine receptors. J. Pharmacol. Exp. Ther. 301, 1052-1059 (2002) https://doi.org/10.1124/jpet.301.3.1052
  83. Kimura, T., Saunders, P. A., Kim, H. S., Rheu, H. M., Oh, K. W. and Ho, I. K.: Interactions of ginsenosides with ligand-bindings of GABA(A) and GABA(B) receptors. Gen. Pharmacol. 25, 193-199 (1994) https://doi.org/10.1016/0306-3623(94)90032-9
  84. 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. Arch. Pharm. Res. 26, 28-33 (2003) https://doi.org/10.1007/BF03179927
  85. Yamaguchi, Y., Higashi, M. and Kobayashi, H.: Effects of ginsenosides on impaired performance caused by scopolamine in rats. Eur. J. Pharmacol. 312,149-151 (1996) https://doi.org/10.1016/0014-2999(96)00597-3
  86. 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. J. Neurosci. Res. 63, 509-915 (2001) https://doi.org/10.1002/jnr.1045
  87. Kennedy, D. O. and Scholey, A. B.: Ginseng: potential for the enhancement of cognitive performance and mood. Pharmacol. Biochem. Behav. 75, 687-700 (2003) https://doi.org/10.1016/S0091-3057(03)00126-6
  88. Terasawa, K., Shimada, Y. and Kita, T.: Choto-san in the treatment of vascular dementia: a double blind, placebo-controlled study. Phytomedicine 4,15-22 (1997) https://doi.org/10.1016/S0944-7113(97)80022-0
  89. Kurimoto, H., Nishijo, H., Uwano, T., Yamaguchi, H., Zhong, Y. M., Kawanishi, K. and Ono, T.: Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats. Physiol. Behav. 82,345-355 (2004) https://doi.org/10.1016/j.physbeh.2004.04.001
  90. Shen, L. and Zhang, J.: Ginsenoside $Rb_1$ increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils. Neurosci. Lett. 344, 1-4 (2003) https://doi.org/10.1016/S0304-3940(03)00318-5
  91. Persson, J., Bringlov, E., Nilsson, L. G. and Nyberg, L.: The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers. Psychopharmacology 172, 430-434 (2004) https://doi.org/10.1007/s00213-003-1675-8

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