DOI QR코드

DOI QR Code

Effect of the Extract of Hydrangea Dulcis Folium on Alcohol-induced Psychiatric Deficits

수국 추출물이 알코올로 유도한 기억 장애 및 long-term potentiation 억제에 미치는 영향

  • Kim, Dong Hyun (Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University) ;
  • Park, Hye Jin (Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University) ;
  • Jung, Ji Wook (Division of Bio-technology and Convergence, College of Herbal Bio-industry, Daegu Haany University) ;
  • Lee, Seungheon (Department of Marine Life Sciences, School of Marine Biomedical Sciences, College of Ocean Sciences, Jeju National University)
  • 김동현 (동아대학교 건강과학대학 의약생명공학과) ;
  • 박혜진 (동아대학교 건강과학대학 의약생명공학과) ;
  • 정지욱 (대구한의대학교 바이오산업대학 바이오산업융합학부) ;
  • 이승헌 (제주대학교 해양과학대학 해양생명과학과)
  • Received : 2017.01.26
  • Accepted : 2017.03.08
  • Published : 2017.03.30

Abstract

Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. This incoordination of blackout may be a major cause in various social problems in alcohol consumption. However, there is still no treatment for preventing these alcohol-induced problems. Hydrangeae dulcis folium is a drug or a tea which is made from the fermented and dried leaves of Hydrangea serrata Seringe. The present study, we tested the ethanol extract of the Hydrangeae dulcis folium (EHDF) on ethanol-induced psychological deficits. To test behavioral deficits, an object recognition test was conducted using a mouse model. To evaluate synaptic deficits, N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential EPSP and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. In the tests, ethanol (1 g/kg, i.p.) impaired object recognition memory, but EHDF (10 or 30 mg/kg) prevented this impairment in object recognition test. Interestingly, EHDF ($30{\mu}g/ml$) significantly ameliorated ethanol-induced LTP and NMDA receptor-mediated synaptic transmission in the hippocampal slices. EHDF prevented ethanol-induced object recognition memory deficits induced by ethanol. Interestingly, EHDF significantly ameliorated ethanol-induced LTP and NMDA receptor- mediated synaptic transmission in the hippocampal slices.

다량의 에탄올을 섭취하면 기억 상실로 이어질 수 있으며, 종종 blackout으로 나타난다. Blackout의 불균형은 알코올 소비에 있어 다양한 사회 문제의 주요 원인이 될 수 있다. 그러나 이러한 알코올 유발 문제를 예방하는 치료법은 아직 존재하지 않는다. Hydrangeae dulcis folium은 Hydrangea serrata Seringe의 잎을 발효가공을 통해 만든 민간약 또는 차이다. 본 연구에서는 에탄올로 유도한 정신적 결핍에 대한 Hydrangeae dulcis folium의 에탄올 추출물(EHDF)의 효과를 평가하였다. 행동적 결핍 또는 장애를 테스트하기 위해 마우스에서 물체 인식 테스트가 수행하였다. 또한 시냅스 결손을 평가하기 위해, 마우스 해마 조각에서 에탄올에 취약한 것으로 알려져 있고 에탄올로 유발한 기억 상실과 관련이 있는 N-methyl-D-aspartate (NMDA) 수용체-매개 흥분성 시냅스 후 전위 및 long-term potentiation (LTP)을 측정하였다. 본 연구에서 에탄올(1 g/kg, i.p.)은 물체 인식 메모리를 손상 시켰지만, EHDF (10 또는 30 mg/kg)는 물체 인식 테스트에서 이러한 장애를 극복하였다. 흥미롭게도, EHDF ($30{\mu}g/ml$)는 해마 절편에서 에탄올 처리 후 억제되었던 LTP 및 NMDA 수용체 매개 시냅스 전달을 유의하게 개선시켰다. EHDF는 에탄올에 의해 유발된 물체 인식 기억력 결핍을 개선하였고, 또한 EHDF는 해마 절편에서 에탄올 유도성 LTP 및 NMDA 수용체 매개성 시냅스 전달을 상당히 개선시켰다.

Keywords

References

  1. Alvestad, R. M., Grosshans, D. R., Coultrap, S. J., Nakazawa, T., Yamamoto, T. and Browning, M. D. 2003. Tyrosine dephosphorylation and ethanol inhibition of N-Methyl-D-aspartate receptor function. J. Biol. Chem. 278, 11020-11025. https://doi.org/10.1074/jbc.M210167200
  2. Castillo, P. E., Weisskopf, M. G. and Nicoll, R. A. 1994. The role of $Ca^{2+}$ channels in hippocampal mossy fiber synaptic transmission and long-term potentiation. Neuron 12, 261-269. https://doi.org/10.1016/0896-6273(94)90269-0
  3. Chandler, L. J., Sutton, G., Norwood, D., Sumners, C. and Crews, F. T. 1997. Chronic ethanol increases N-methyl-D-aspartate-stimulated nitric oxide formation but not receptor density in cultured cortical neurons. Mol. Pharmacol. 51, 733-740. https://doi.org/10.1124/mol.51.5.733
  4. Chandler, L. J. 2003. Ethanol and brain plasticity: receptors and molecular networks of the postsynaptic density as targets of ethanol. Pharmacol. Ther. 99, 311-326. https://doi.org/10.1016/S0163-7258(03)00096-2
  5. Chandrasekar, R. 2013. Alcohol and NMDA receptor: current research and future direction. Front. Mol. Neurosci. 6, 14.
  6. Cohen, S. and Greenberg, M. E. 2008. Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Ann. Rev. Cell Dev. Biol. 24, 183-209. https://doi.org/10.1146/annurev.cellbio.24.110707.175235
  7. Dodd, P. R., Beckmann, A. M., Davidson, M. S. and Wilce, P. A. 2000. Glutamate-mediated transmission, alcohol, and alcoholism. Neurochem. Int. 37, 509-533. https://doi.org/10.1016/S0197-0186(00)00061-9
  8. Gulick, D. and Gould, T. J. 2009. Effects of ethanol and caffeine on behavior in C57BL/6 mice in the plus-maze discriminative avoidance task. Behav. Neurosci. 123, 1271-1278. https://doi.org/10.1037/a0017610
  9. Hicklin, T. R., Wu, P. H., Radcliffe, R. A., Freund, R. K., Goebel-Goody, S. M., Correa, P. R., Proctor, W. R., Lombroso, P. J. and Browning, M. D. 2011. Alcohol inhibition of the NMDA receptor function, long-term potentiation, and fear learning requires striatal-enriched protein tyrosine phosphatase. Proc. Natl. Acad. Sci. USA 108, 6650-6655. https://doi.org/10.1073/pnas.1017856108
  10. Izumi, Y., Nagashima, K., Murayama, K. and Zorumski, C. F. 2005. Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms. Neuroscience 136, 509-517. https://doi.org/10.1016/j.neuroscience.2005.08.002
  11. Jaffe, D. and Johnston, D. 1990. Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule. J. Neurophysiol. 64, 948-960. https://doi.org/10.1152/jn.1990.64.3.948
  12. Johnston, D., Williams, S., Jaffe, D. and Gray, R. 1992. NMDA-receptor-independent long-term potentiation. Ann. Rev. Physiol. 54, 489-505. https://doi.org/10.1146/annurev.ph.54.030192.002421
  13. Kamei, K., Matsuoka, H., Furuhata, S. I., Fujisaki, R. I., Kawakami, T., Mogi, S., Yoshihara, H., Aoki, N., Ishii, A. and Shibuya, T. 2000. Anti-malarial activity of leaf-extract of hydrangea macrophylla, a common Japanese plant. Acta Med. Okayama 54, 227-232.
  14. Kawamura, M., Kagata, M., Masaki, E. and Nishi, H. 2002. Phyllodulcin, a constituent of "Amacha", inhibits phosphodiesterase in bovine adrenocortical cells. Pharmacol. Toxicol. 90, 106-108. https://doi.org/10.1034/j.1600-0773.2002.900209.x
  15. Komatsu, Y., Nakajima, S. and Toyama, K. 1991. Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex. J. Neurophysiol. 65, 20-32. https://doi.org/10.1152/jn.1991.65.1.20
  16. Koordeman, R., Anschutz, D. J. and Engels, R. C. 2014. Self-control and the effects of movie alcohol portrayals on immediate alcohol consumption in male college students. Front. Psychiatry 5, 187.
  17. Liguori, A. and Robinson, J. H. 2001. Caffeine antagonism of alcohol-induced driving impairment. Drug Alcohol Depend. 63, 123-129. https://doi.org/10.1016/S0376-8716(00)00196-4
  18. McCool, B. A. 2011. Ethanol modulation of synaptic plasticity. Neuropharmacology 61, 1097-1108. https://doi.org/10.1016/j.neuropharm.2010.12.028
  19. Otmakhov, N., Khibnik, L., Otmakhova, N., Carpenter, S., Riahi, S., Asrican, B. and Lisman, J. 2004. Forskolin-induced LTP in the CA1 hippocampal region is NMDA receptor dependent. J. Neurophysiol. 91, 1955-1962. https://doi.org/10.1152/jn.00941.2003
  20. Silveri, M. M. and Spear, L. P. 2002. The effects of NMDA and GABAA pharmacological manipulations on ethanol sensitivity in immature and mature animals. Alcohol. Clin. Exp. Res. 26, 449-456. https://doi.org/10.1111/j.1530-0277.2002.tb02560.x
  21. Spinetta, M. J., Woodlee, M. T., Feinberg, L. M., Stroud, C., Schallert, K., Cormack, L. K. and Schallert, T. 2008. Alcohol-induced retrograde memory impairment in rats: prevention by caffeine. Psychopharmacology 201, 361-371. https://doi.org/10.1007/s00213-008-1294-5
  22. Tabakoff, B., Whelan, J. P., Ovchinnikova, L., Nhamburo, P., Yoshimura, M. and Hoffman, P. L. 1995. Quantitative changes in G proteins do not mediate ethanol-induced downregulation of adenylyl cyclase in mouse cerebral cortex. Alcohol. Clin. Exp. Res. 19, 187-194. https://doi.org/10.1111/j.1530-0277.1995.tb01491.x
  23. Yi, J. H., Park, H. J., Kim, B. C., Kim, D. H. and Ryu, J. H. 2016. Evidences of the role of the rodent hippocampus in the non-spatial recognition memory. Behav. Brain Res. 297, 141-149. https://doi.org/10.1016/j.bbr.2015.10.018
  24. Zhang, H., Matsuda, H., Kumahara, A., Ito, Y., Nakamura, S. and Yoshikawa, M. 2007. New type of anti-diabetic compounds from the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium). Bioor. Med. Chem. Lett 17, 4972-4976. https://doi.org/10.1016/j.bmcl.2007.06.027
  25. Zhang, H., Matsuda, H., Yamashita, C., Nakamura, S. and Yoshikawa, M. 2009. Hydrangeic acid from the processed leaves of Hydrangea macrophylla var. thunbergii as a new type of anti-diabetic compound. Eur. J. Pharmacol. 606, 255-261. https://doi.org/10.1016/j.ejphar.2009.01.005