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Promotive Effects of Yokukansan, a Traditional Japanese Medicine, on Proliferation and Differentiation of Cultured Mouse Cortical Oligodendrocytes

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DOI: 10.4236/pp.2014.57077    3,089 Downloads   3,749 Views   Citations

ABSTRACT

Effects of yokukansan, a traditional Japanese medicine, on proliferation and differentiation of oligodendrocytes were examined using purified mouse cortical oligodendrocyte precursor cells (OPCs). OPCs were cultured for four days, and proliferation was evaluated by counting A2B5 (a specific antibody to OPC)-reactive cells on the second day of cell culture. Differentiation from OPC to oligodendrocyte was evaluated by counting O4 (a specific antibody to detect differentiated cells in various stages)-reactive cells on the fourth day of culture. The effects of yokukansan (final concentration: 100 or 200 μg/ml) on proliferation and differentiation were examined by adding it to the medium for four days. Yokukansan increased not only the number of A2B5-positive cells on the second day but also the number of O4-positive cells on the fourth day compared to those in the corresponding controls. A WST-8 assay was used to identify active components from seven components of Uncaria Hook (UH), one of the constituent galenicals of yokukansan. Geissoschizine methyl ether (GM: 0.1 - 3.0 μM) was identified by this screening assay and increased the number of A2B5-positive cells on the second day and O4-positive cells on the fourth day as yokukansan did. These results suggest that yokukansan promotes the proliferation and differentiation of oligodendrocytes, and also that GM contained in UH is one of active components responsible for this effect of yokukansan.

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The authors declare no conflicts of interest.

Cite this paper

Ueki, T. , Ikarashi, Y. , Kawakami, Z. , Mizoguchi, K. and Kase, Y. (2014) Promotive Effects of Yokukansan, a Traditional Japanese Medicine, on Proliferation and Differentiation of Cultured Mouse Cortical Oligodendrocytes. Pharmacology & Pharmacy, 5, 670-680. doi: 10.4236/pp.2014.57077.

References

[1] Keirstead, H.S. and Blakemore, W.F. (1999) The Role of Oligodendrocytes and Oligodendrocyte Progenitors in CNS Remyelination. Advances in Experimental Medicine and Biology, 468, 183-197.
http://dx.doi.org/10.1007/978-1-4615-4685-6_15
[2] Morrell, P. and Quarles, R.H. (1999) Myelin Formation, Structure and Biochemistry. In: Siegel, G.J., Agranoff, B.W., Alber, R.W., Risher, S.K. and Uhler, M.D., Eds., Basic Neurochemistry, 6th Edition, Raven Press, New York, 70-93.
[3] Baer, A.S., Syed, Y.A., Kang, S.U., Mitteregger, D., Vig, R., Ffrench-Constant, C., Franklin, B.J.M., Altmann, F., Lubec, G. and Kotter, M.R. (2009) Myelin-Mediated Inhibition of Oligodendrocyte Precursor Differentiation Can Be Overcome by Pharmacological Modulation of Fyn-RhoA and Protein Kinase C Signaling. Brain, 132, 465-481.
http://dx.doi.org/10.1093/brain/awn334
[4] Mi, S., Miller, R.H., Tang, W., Lee, X., Hu, B., Wu, W., Zhang, Y., Shields, C.B., Zhang, Y., Miklasz, S., Shea, D., Mason, J., Franklin, R.J.M., Ji, B., Jung, V. and Pepinsky, B. (2009) Promotion of Clinical Nervous System Remyelination by Induced Differentiation of Oligodendrocyte Precursor Cells. Annals of Neurology, 65, 304-315.
http://dx.doi.org/10.1002/ana.21581
[5] Kobayashi, J., Seiwa, C., Sakai, T., Gotoh, M., Komatsu, Y., Yamamoto, M., Fukutake, M., Matsuno, K., Sakurai, Y., Kawano, Y. and Asou, H. (2003) Effect of a Traditional Chinese Herbal Medicine, Ren-Shen-Yang-Rong-Tang (Japanese Name: Ninjin-Youei-To), on Oligodendrocyte Precursor Cells from Aged-Rat Brain. International Immunopharmacology, 3, 1027-1039.
http://dx.doi.org/10.1016/S1567-5769(03)00101-2
[6] Akundi, R.S. and Rivkees, S.A. (2009) Hypoxia Alters Cell Cycle Regulatory Protein Expression and Induces Premature Maturation of Oligodendrocyte Precursor Cells. PLoS ONE, 4, Article ID: e4739.
http://dx.doi.org/10.1371/journal.pone.0004739
[7] Hazell, A.S., Todd, K.G. and Butterworth, R.F. (1998) Mechanism of Neuronal Cell Death in Wernicke’s Encephalopathy. Metabolic Brain Disease, 13, 97-122.
http://dx.doi.org/10.1023/A:1020657129593
[8] Seiwa, C., Kojima-Akikawa, K., Matsumoto, I. and Asou, H. (2002) CNS Myelinogenesis in Vitro: Myelin Basic Protein Deficient Shiverer Oligodendrocytes. Journal of Neuroscience Research, 69, 305-317.
http://dx.doi.org/10.1002/jnr.10291
[9] Seiwa, C., Yamamoto, M., Tanaka, K., Fukutake, M., Ueki, T., Takeda, S., Sakai, R., Ishige, A., Watanabe, K., Akita, M., Yagi, T., Tanaka, K. and Asou, H. (2007) Restoration of FcRγ/Fyn Signaling Repairs Central Nervous System Demyelination. Journal of Neuroscience Research, 85, 954-966.
http://dx.doi.org/10.1002/jnr.21196
[10] Iwasaki, K., Satoh-Nakagawa, T., Maruyama, M., Monma, Y., Nemoto, M., Tomita, N., Tanji, H., Fujiwara, H., Seki, T., Fujii, M., Arai, H. and Sasaki, H. (2005) A Randomized, Observer-Blind, Controlled Trial of the Traditional Chinese Medicine Yi-Gan San for Improvement of Behavioral and Psychological Symptoms and Activities of Daily Living in Dementia Patients. Journal of Clinical Psychiatry, 66, 248-252.
http://dx.doi.org/10.4088/JCP.v66n0214
[11] Iwasaki, K., Kosaka, K., Mori, H., Okitsu, R., Furukawa, K., Manabe, Y., Yoshita, M., Kanamori, A., Ito, N., Wada, K., Kitayama, M., Horiguchi, J., Yamaguchi, S., Katayama, S., Fukuhara, R., Ouma, S., Nakano, S., Hashimoto, M. and Kinoshita, T. (2012) Improvement in Delusions and Halucinations in Patients with Dementia with Lewy Bodies upon Administration of Yokykansan, a Traditional Japanese Medicine. Psychogeriatrics, 12, 235-241.
http://dx.doi.org/10.1111/j.1479-8301.2012.00413.x
[12] Mizukami, K., Asada, T., Kinoshita, T., Tanaka, K., Sonohara, K., Nakai, R., Yamaguchi, K., Hanyu, H., Kanaya, K., Takao, T., Okada, M., Kudo, S., Kotoku, H., Iwakiri, M., Kurita, H., Miyamura, T., Kawasaki, Y., Omori, K., Shiozaki, K., Odawara, T., Suzuki, T., Yamada, S., Nakamura, Y. and Toba, K. (2009) A Randomized Cross-Over Study of a Traditional Japanese Medicine (Kampo), Yokukansan, in the Treatment of the Behavioural and Psychological Symptoms of Dementia. The International Journal of Neuropsychopharmacology, 12, 191-199.
http://dx.doi.org/10.1017/S146114570800970X
[13] Nagata, K., Yokoyama, E., Yamazaki, T., Takano, D., Maeda, T., Takahashi, S. and Terayama, Y. (2012) Effects of Yokukansan on Behavioral and Psychological Symptoms of Vascular Dementia: Open-Label Trial. Phytomedicine, 19, 524-528.
http://dx.doi.org/10.1016/j.phymed.2012.02.008
[14] Matsuda, Y., Kishi, T., Shibayama, H. and Iwata, N. (2013) Yokukansan in the Treatment of Behavioral and Psychological Symptoms of Dementia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Human Psychopharmacology: Clinical and Experimental, 28, 80-86.
http://dx.doi.org/10.1002/hup.2286
[15] Ikarashi, Y., Iizuka, S., Imamura, S., Yamaguchi, T., Sekiguchi, K., Kanno, H., Kawakami, Z., Yuzurihara, M., Kase, Y. and Takeda, S. (2009) Effects of Yokukansan, a Traditional Japanese Medicine, on Memory Disturbance and Behavioral and Psychological Symptoms of Dementia in Thiamine-Deficient Rats. Biological & Pharmaceutical Bulletin, 32, 1701-1709.
http://dx.doi.org/10.1248/bpb.32.1701
[16] Iizuka, S., Kawakami, Z., Imamura, S., Yamaguchi, T., Sekiguchi, K., Kanno, H., Ueki, T., Kase, Y. and Ikarashi, Y. (2010) Electron-Microscopic Examination of Effects of Yokukansan, a Traditional Japanese Medicine, on Degeneration of Cerebral Cells in Thiamine-Deficient Rats. Neuropathology, 30, 524-536.
http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1789.2010.01101.x/full
[17] Fujiwara, H., Takayama, S., Iwasaki, K., Tabuchi, M., Yamaguchi, T., Sekiguchi, K., Ikarashi, Y., Kudo, Y., Kase, Y., Arai, H. and Yaegashi, N. (2011) Yokukansan, a Traditional Japanese Medicine, Ameliorates Memory Disturbance and Abnormal Social Interaction with Anti-Aggregation Effect of Cerebral Amyloid β Proteins in Amyloid Precursor Protein Transgenic Mice. Neuroscience, 180, 305-313.
http://dx.doi.org/10.1016/j.neuroscience.2011.01.064
[18] Nishi, A., Yamaguchi, T., Sekiguchi, K., Imamura, S., Tabuchi, M., Kanno, H., Nakai, Y., Hashimoto, K., Ikarashi, Y. and Kase, Y. (2012) Geissoschizine Methyl Ether, an Alkaloid in Uncaria Hook, Is a Potent Serotonin1A Receptor Agonist and Candidate for Amelioration of Aggressiveness and Sociality by Yokukansan. Neuroscience, 201, 124-136.
http://dx.doi.org/10.1016/j.neuroscience.2012.01.037
[19] Kawakami, Z., Kanno, H., Ikarashi, Y. and Kase, Y. (2011) Yokukansan, a Kampo Medicine, Protects against Glutamate Cytotoxicity Due to Oxidative Stress in PC12 Cells. Journal of Ethnopharmacology, 134, 74-81.
http://dx.doi.org/10.1016/j.jep.2010.11.063
[20] Yuzurihara, M., Ikarashi, Y., Goto, K., Sakakibara, I., Hayakawa, T. and Sasaki, H. (2002) Geissoschizine Methyl Ether, an Indole Alkaloid Extracted from Uncariae Ramulus et Uncus, Is a Potent Vasorelaxant of Isolated Rat Aorta. European Journal of Pharmacology, 444, 183-189.
http://dx.doi.org/10.1016/S0014-2999(02)01623-0
[21] Ueki, T., Tsuruo, Y., Yamamoto, Y., Yoshimura, K., Takanaga, H., Seiwa, C., Motojima, K., Asou, H. and Yamamoto, M. (2012) A New Monoclonal Antibody, 4F2, Specific for the Oligodendroglial Cell Lineage, Recognizes ATP-Dependent RNA Helicase Ddx54: Possible Association with Myelin Basic Protein. Journal of Neuroscience Research, 90, 48-59.
http://dx.doi.org/10.1002/jnr.22736
[22] Ishiyama, M., Miyazono, Y., Sasamoto, K., Ohkura, Y. and Ueno, K. (1997) A Highly Water-Soluble Disulfonated Tetrazolium Salt as a Chromogenic Indicator for NADH as Well as Cell Viability. Talanta, 44, 1299-1305.
http://dx.doi.org/10.1016/S0039-9140(97)00017-9
[23] Arai, K. and Lo, E.H. (2010) Astrocytes Protect Oligodendrocyte Precursor Cell via MEK/ERK and PI3K/Akt Signaling. Journal of Neuroscience Research, 88, 758-763.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705578/
[24] Bibollet-Bahena, O. and Almazan, G. (2009) IGF-1-Stimulated Protein Synthesis in Oligodendrocyte Progenitors Requires PI3K/mTOR/Akt and MEK/ERK Pathways. Journal of Neurochemistry, 109, 1440-1451.
http://dx.doi.org/10.1111/j.1471-4159.2009.06071.x
[25] Fyffe-Maricich Karlo, J.C., Landreth, G.E. and Miller, R.H. (2011) The ERK2 Mitogen-Activated Protein Kinase Regulates the Timing of Oligodendrocyte Differentiation. The Journal of Neuroscience, 31, 843-850.
http://dx.doi.org/10.1523/JNEUROSCI.3239-10.2011
[26] Vaudry, D., Stork, P.J., Lazarovici, P. and Eiden, L.E. (2002) Signaling Pathways for PC12 Cell Differentiation: Making the Right Connections. Science, 296, 1648-1649.
http://dx.doi.org/10.1126/science.1071552
[27] Hetman, M. and Gozdz, A. (2004) Role of Extracellular Signal Regulated Kinases 1 and 2 in Neuronal Survival. European Journal of Biochemistry, 271, 2050-2055.
http://dx.doi.org/10.1111/j.1432-1033.2004.04133.x
[28] Chen, J.Y., Lin, J.R., Cimprich, K.A. and Meyer, T. (2012) Two-Dimensional ERK-AKT Signaling Code for an NGF-Triggered Cell-Fate Decision. Molecular Cell, 45, 196-209.
http://dx.doi.org/10.1016/j.molcel.2011.11.023
[29] Kubota, K., Sano, K., Shiraishi, A., Beppu, N., Nogami, A., Uchida, N., Takasaki, K., Katsurabayashi, S., Mishima, K., Nishimura, R., Fujiwara, M. and Iwasaki, K. (2013) Yokukansan, a Traditional Japanese Herbal Medicine, Promotes Neurite Outgrowth in PC12 Cells through the Activation of Extracellular Signal Regulated Kinase 1/2 and Phosphatidylinositol 3-Kinase/Akt. Journal of Traditional Medicines, 30, 102-113.
[30] Kawakami, Z., Kanno, H., Ikarashi, Y. and Kase, Y. (2011) Isoliquiritigenin Is a Novel NMDA Receptor Antagonist in Kampo Medicine Yokukansan. Cellular and Molecular Neurobiology, 31, 1203-1212.
http://dx.doi.org/10.1007/s10571-011-9722-1
[31] Tanaka, Y. and Mizoguchi, K. (2009) Influence of Aging on Chondroitin Sulfate Proteoglycan Expression and Neural Stem/Progenitor Cells in Rat Brain and Improving Effects of a Herbal Medicine, Yokukansan. Neuroscience, 164, 1224-1234.
http://dx.doi.org/10.1016/j.neuroscience.2009.08.060
[32] Shimada, Y., Goto, H., Ito, T., Sakakibara, I., Kubo, M., Sasaki, S. and Terasawa, K. (1999) Evaluation of the Protective Effects of Alkaloids Isolated from the Hooks and Stems of Uncaria sinensis on Glutamate-Induced Neuronal Death in Cultured Cerebellar Granule Cells from Rats. Journal of Pharmacology and Pharmacotherapeutics, 51, 715-722.
http://dx.doi.org/10.1211/0022357991772853
[33] Suk, K., Kim, S.Y., Leem, K., Kim, Y.O., Parl, S.Y., Hur, J., Beak, J., Lee, K.J., Zheng, H.Z. and Kim, H. (2002) Neuroprotection by Methanol Extract of Uncaria rhynchophylla against Global Cerebral Ischemia in Rats. Life Sciences, 70, 2467-2480.
http://dx.doi.org/10.1016/S0024-3205(02)01534-5
[34] Lee, J., Son, D., Lee, P., Kim, S.-T., Kim, H., Kim, C.-J. and Lim, E. (2003) Alkaloid Fraction of Uncaria rhynchophylla Protects against N-Methyl-D-Aspartate-Induced Apoptosis in Rat Hippocampal Slices. Neuroscience Letters, 348, 51-55.
http://dx.doi.org/10.1016/S0304-3940(03)00613-X
[35] Shim, J.S., Kim, H.G., Ju, M.S., Choi, J.G., Jeong, S.Y. and Oh, M.S. (2009) Effect of the Hook of Uncaria rhynchophylla on Neurotoxicity in the 6-Hydroxydopamine Model of Parkinson’s Disease. Journal of Ethnopharmacology, 126, 361-365.
http://dx.doi.org/10.1016/j.jep.2009.08.023
[36] Morita, S., Tatsumi, K., Makinodan, M., Okuda, H., Kishimoto, T. and Wanaka, A. (2014) Geissoschizine Methyl Ether, an Alkaloid from the Uncaria Hook Improves Remyelination after Cuprizone-Induced Demyelination in Medial Prefrontal Cortex of Adult Mice. Neurochemical Research, 39, 59-67.
http://dx.doi.org/10.1007/s11064-013-1190-1
[37] Imamura, S., Tabuchi, M., Kushida, H., Nishi, A., Kanno, H., Yamaguchi, T., Sekiguchi, K., Ikarashi, Y. and Kase, Y. (2011) The Blood-Brain Barrier Permeability of Geissoschizine Methyl Ether in Uncaria Hook, a Galenical Constituent of the Traditional Japanese Medicine Yokukansan. Cellular and Molecular Neurobiology, 31, 787-793.
http://dx.doi.org/10.1007/s10571-011-9676-3
[38] Kawakami, Z., Ikarashi, Y. and Kase, Y. (2010) Glycyrrhizin and Its Metabolite 18 Beta-Glycyrrhetinic Acid in Glycyrrhiza, a Constituent Herb of Yokukansan, Ameliorate Thiamine Deficiency-Induced Dysfunction of Glutamate Transport in Cultured Rat Cortical Astrocytes. European Journal of Pharmacology, 626, 154-158.
http://dx.doi.org/10.1016/j.ejphar.2009.09.046
[39] Baron, W., de Jonge, J.C., de Vries, H. and Hoekstra, D. (1998) Regulation of Oligodendrocyte Differentiation: Protein Kinase C Activation Prevents Differentiation of O2A Progenitor Cells toward Oligodendrocytes. Glia, 22, 121-129.
http://dx.doi.org/10.1002/(SICI)1098-1136(199802)22:2<121::AID-GLIA3>3.0.CO;2-A

  
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