Journal of agriculture & life science (농업생명과학연구)

Institute of Agriculture & Life Science, Gyeongsang National University (경상대학교 농업생명과학연구원)
권호 표지

Screeening of Natural Plant Resources with Acetylcholine esterase inhibitory activity and Effect on Scopolamine-induced Memory Impairment

천연식물자원으로부터 Acetylcholine esterase 저해 활성 탐색 및 인지기능에 미치는 영향

  • 최장원 (대구대학교 바이오산업학과) ;
  • 원무호 (강원대학교 신경생물학실) ;
  • 주한승 (씨앤제이바이오텍(주))
  • Received : 2011.11.14
  • Accepted : 2011.12.20
  • Published : 2011.12.30
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Abstract

This study was performed to investigate the effect of essential oils and ethanolic extracts of approximately 650 plant species on acetylcholine esterase (AChE) enzyme activity using Ellman's colorimetric method in 96-well microplates. The results showed that the ethanolic extracts from twig of Sophora subprostrata, twig of Phellodendron amurense, seed of Corylopsis coreana, and essential oil (EO) from Citrus paradisi, Cupressus sempervirens, Ocimum basilicum, Pinus sylvestris and Rosmarinus officinalis inhibited more than 80% of AChE activity. Among these, EO from Pinus sylvestris, C. sempervirens and C paradisi exhibited higher values of AChE inhibitory activity, which were 75, 84 and 99% at a concentration of 50 ug/ml, respectively. Finally, EO from C paradisi (grapefruit, GEO) showed the highest inhibitory activity towards AChE, which showed 91% of inhibition at a concentration of 20 ug/ml. We also examined the anti-dementia effects of GEO in mouse by passive avoidance test and Morris water maze test. The model mouse (male, ICR) of dementia (negative control) was induced by administration of scopolamine (1 mg/kg body weight). The latency time of sample group administrated with GEO (100 mg/kg, p.o.) increased significantly as compared with negative control on passive avoidance test. There were significant recovery from the scopolamine-induced deficits on learning and memory in water maze test through daily administrations with GEO (100 mg/kg, p.o.). From these results, we conclude that GEO treatment might enhance the cognitive function, suggesting that the EO of C. paradis may be a potential candidate for improvement of perceptive ability and dementia.

아세틸콜린 분해효소(acetylcholine esterase, AChE) 억제제는 아세틸콜린 함량을 높여 콜린성 neuron을 활성화함으로써 기억 능력의 개선 및 치매 개선을 가져와 현재 다양한 AChE 억제제들이 개발되어 사용되고 있다. 본 연구에서는 AChE에 대한 억제 활성을 갖는 천연물을 다양한 식물추출물 및 에센스오일로부터 탐색하였으며, 탐색한 추출물의 scopolamine으로 기억손상을 유발한 쥐의 기억력 개선 활성을 치매 치료제로 사용하고 있는 donepizil과 비교 분석하였다. 그 결과 자몽(Citrus paradisi) 유래의 에센스 오일이 AChE 억제 활성이 가장 높아 20 ug/ml의 농도로 처리하였을 때 90% 이상의 효소 억제 활성을 나타내었다. 수동회피 실험 결과, 자몽 유래의 에센스오일(100 mg/kg, p.o.)을 투여한 쥐는 치매 치료제로 사용하고 있는 donepizile (0.5 mg/kg)을 투여한 쥐와 유사한 latency time을 나타내어 인지기능이 개선되었다. 또한, 수중미로 시험 결과, 자몽 유래 에센스오일(100 mg/Kg, p.o.)을 투여한 쥐는 donepizile(0.5 mg/kg)을 투여한 쥐와 유사한 latency time을 나타내어 인지기능이 개선되었다. 이상의 결과로부터 자몽 유래 에센스오일은 매우 효과적으로 기억력을 개선하여 인지기능을 개선해 줄 수 있는 안전하고 효과적인 후보물질이라고 사료된다.

Keywords

References

  1. Adams R. L., P. L. Craig, and O. A. Parsons. 1984. Neuropsychology of dementia. Neurolog. Clin. 4: 387-405.
  2. Barnham K. J., C. L. Masters, and A. I. Bush. 2004. Neurodegenerative diseases and oxidative stress. Nature. Rev. Drug Discovery. 3: 205-214. https://doi.org/10.1038/nrd1330
  3. Borjesson-Hanson A., E. Edin, T. Gislason, and I. Skoog. 2004. The prevalence of dementia in 95 year olds. Neurol. 63: 2436-2438. https://doi.org/10.1212/01.WNL.0000147260.52841.27
  4. Butini S., E. Guarino, G. Campiani, M. Brindisi, S. S. Coccone, I. Fiorini, E. Novellino, T. Belinskaya, A. Saxena, and S. Gemmaa. 2008. Tacrine based human cholinesterase inhibitors: Synthesis of peptidic-tethered derivatives and their effect on potency and selectivity. Bioorganic Med. Chem. Lett. 18: 5213-5216. https://doi.org/10.1016/j.bmcl.2008.08.076
  5. Chung Y. K., H. J. Heo, E. K. Kim, H. K. Kim, T. L. Huh, Y. Lim, S. K. Kim, and D. H. Shin. 2001. Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase. Mol. Cells. 11: 137-143.
  6. Citron M. 2004. Strategies for disease modification in Alzheimer's disease. Nature Rev. Neurosci. 5: 677-685.
  7. Cottingham M. G., J. L. Voskuil, and D. J. Vaux. 2003. The intact human acetylcholinesterase c-terminal oligomerization domain is alpha-helical in situ and in isolation, but a shorter fragment forms beta-sheet-rich amyloid fibrils and protofibrillar oligomers. Biochem. 42: 10863-10873. https://doi.org/10.1021/bi034768i
  8. Cummings J. L. 2000. Cholinesterase inhibitors: a new class of psychotropic compounds. Am. J. Psychiatry. 157: 4-15.
  9. Cummings J. L. 2004. Alzheimer's Disease. Nwe. Engl. J. Med. 351: 56-67. https://doi.org/10.1056/NEJMra040223
  10. de Lau, L. M. and M. M. Breteler. 2006. Epidemiology of Parkinson's disease. Lancet Neurol. 5: 525-535. https://doi.org/10.1016/S1474-4422(06)70471-9
  11. Ellman G. L., D. K. Courtney, V. Andres, and R. M. Featherstone. 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  12. Enz A., R. Amstutz, H. Boddeke, G. Gmelin, and J. Malonowski. 1993. Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer's disease. Prog. Brain Res. 98: 431-445.
  13. Fayuk D. and J. L. Yakel. 2004. Regulation of nicotinic acetylcholine receptor channel function by acetylcholinesterase inhibitors in rat hippocampal CA1 interneurons. Mol. Pharmacol. 66: 658-666. https://doi.org/10.1124/mol.104.000042
  14. Findeis M. A. 2007. The role of amyloid $\beta$ peptide 42 in Alzheimer's disease. Pharmacol. Therapeut. 116: 266-286. https://doi.org/10.1016/j.pharmthera.2007.06.006
  15. Grossberg G., P. Irwin, and A. Satlin. 2004. Rivastigmine in Alzheimer's disease: efficacy over two years. Am. J. Geriatr. Psychiatry. 12: 420-431.
  16. Ingkaninan K., P. Temkitthawon, K. Chuenchom, T. Yuyaem, and W. Thongnoi. 2003. Screening for acetylcholin esterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies. J. Ethnopharmacol. 89: 261-264. https://doi.org/10.1016/j.jep.2003.08.008
  17. Johnson N. T. D. and N. Bosanquet. 2000. The epidermic of Alzheimer's disease. Pharmacoeconomics. 18: 215-223. https://doi.org/10.2165/00019053-200018030-00002
  18. Jung J. H. and S. Y. Lee. 2007. AChE Inhibitory Effect and Antioxidative Activity of Submerged Cultured Products from Hericium erinaceum. Kor. J. Biotechnol. Bioeng. 22: 30-36.
  19. Kalauni S. K., M. I. Choudhary, A. Khalid, M. D. Manandhar, F. Shaheen, F. Atta-ur-Rahman, and M. B. Gewali. 2002. New cholinesterase inhibiting steroidal alkaloids from the leaves of Sarcococca coriacea of Nepalese origin. Chem. Pharm. Bull. 50: 1423-1426. https://doi.org/10.1248/cpb.50.1423
  20. Kim D. I., S. H. Lee, E. Y. Hur, S. M. Cho, and H. J. Park. 2005. Screening of Natural Plant Resources with Acetylcholinesterase Inhibition and Antioxidant Activity. J. Kor. Soc. Food Sci. Nutr. 34: 427-432. https://doi.org/10.3746/jkfn.2005.34.3.427
  21. Kim D. K., J. Y. Lee, J. J. Sung, E. T. Kim, Y. S. Kim, O. S. Kwon, Y. C. Yun, T. J. Lee, Y. K. Kang, Y. H. Chung, S. S. Kim, K. Y. Kim, and W. B. Lee. 2004. The Role of BF-7 on Enhancement of Memory and Cognitive Function. The Korean J. Anat. 37: 519-527.
  22. Kim, J. S., Y. S. Kim, S. K. Kim, J. H. Heor, B. H. Lee, B. W. Choi, G. S. Ryu, E. K. Park, O. P Zee, and S. Y. Ryu. 2002. Inhibitory Effects of Some Herbal Extracts on the Acetylcholinesterase (AChE) In Vitro. Kor. J. Pharmacogn. 33: 211-218.
  23. Lee E. H., Y. C. Youn, K. Y. Park,J. H. Min, O. S. Kwon, H. O. Lee, and H. J. Hong. 2009a. The Effect of Acetylcholine Esterase Inhibitor on Cerebrospinal Fluid $\beta$-Amyloid 1-42 and Phosphorylated Tau Protein in Korean Alzheimer's Disease Patients: Preliminary Study. J. Kor. Neurol. Assoc. 26: 224-230.
  24. Lee M. R., B. S. Sun, L. J. Gu, C. Y. Wang, E. K. Mo, S. A. Yang, S. Y. Ly, and C. K. Sung. 2008. Effect of white ginseng extract and red ginseng extract on learning performance and acetylcholinesterase activity inhibition. J. Ginseng Res. 32: 341-346. https://doi.org/10.5142/JGR.2008.32.4.341
  25. Lee M. R., B. S. Sun, L. J. Gu, C. Y. Wang, Z. M. Fang, Z. Wang, E. K. Mo, S. Y. Ly, and C. K. Sung. 2009b. Effect of the Deer Antler Extract on Scopolamine-Induced Memory Impairment and Its Related Enzyme Activities. J. Korean Soc. Food Sci. Nutr.38: 409-414. https://doi.org/10.3746/jkfn.2009.38.4.409
  26. Lemiere J., J. D. Van, and R. Dorn. 1999. Treatment of Alzheimer's disease: an evaluation of cholinergic approach. Acta Neurol. Belg. 99: 96-106.
  27. Mattson M. P. 2004. Pathways towards and away from Alzheimer's disease. Nature 430: 631-639. https://doi.org/10.1038/nature02621
  28. Nussbaum R. L. and C. E. Ellis. 2003. Alzheimer's disease and Parkinson's disease. New Engl. J. Med, 348: 1356-1364. https://doi.org/10.1056/NEJM2003ra020003
  29. Park C. H., S. H. Kim, W. Choi, Y. J. Lee, J. S. Kim, S. S. Kang, and Y. H. Suh. 1996. Novel anticholinesterase and antiamnesic activities of dehydroevodiamine, a constituent of Evodia rutaecarpa. Planta Med. 62: 405-409. https://doi.org/10.1055/s-2006-957926
  30. Park J. Y., S. U Woo, J. C. Heo, and S. H. Lee. 2007. Protective Effects of Helianthus annuus Seed Extract against Chemical-Induced Neuronal Cell Death. Kor. J. Food Preserv. 14: 213-219.
  31. Reale M., C. Iarlori, F. Gambi, C. Feliciani C., L. Isabella, and D. Gambi. 2006. The acetylcholinesterase inhibitor, Donepezil, regulates a Th2 bias in Alzheimer's disease patients. Neuropharmacol. 50: 606-613. https://doi.org/10.1016/j.neuropharm.2005.11.006
  32. Rosengarten B., S. Paulsen, S. Molnar, R. Kaschel, B. Gallhofer, and M. Kaps. 2006. Acetylcholine esterase inhibitor donepezil improves dynamic cerebrovascular regulation in Alzheimer patients. J. Neurol. 253: 58-64. https://doi.org/10.1007/s00415-005-0926-5
  33. Ryu B. H. and S. O. Kim. 2004. Effects of Methanol Extract of Stachys sieboldii MIQ on Acetylcholine Esterase and Monoamine Oxidase in Rat. Kor. J. Food Nutr. 17: 347-355.
  34. Ryu S. Y., Park Y. K. and Kang B. S. 2003. Studies on the Acetylcholinesterase inhibitors Effects of Cuscutae Semen. Kor. J. Herbiol. 18: 289-299.
  35. Sabbagh M. N. 2009. Drug Development for Alzheimer's Disease: Where Are We Now and Where Are We Headed? Am. J. Geriatric Pharmacother. 7: 167-185. https://doi.org/10.1016/j.amjopharm.2009.06.003
  36. Sharp B. M., M. Yatsula, and V. Fu. 2004. Effects of Galantamine, a Nicotinic Allosteric Potentiating Ligand, on Nicotine-Induced Catecholamine Release in Hippocampus and Nucleus Accumbens of Rats. J. Pharmacol. Experimental Therapeut. 309: 1116-1123. https://doi.org/10.1124/jpet.103.063586
  37. Silvestrelli G., A. Lanari, L. Parnetti. D. Tomassoni, and F. Amenta. 2006. Treatment of Alzheimer's disease: from pharmacology to a better understanding of disease pathophysiology. Mech. Ageing Dev. 127: 148-157. https://doi.org/10.1016/j.mad.2005.09.018
  38. Son C. Y., I. H. Baek, G. Y. Song, J. S. Kang, and K. I. Kwon. 2009. Pharmacological Effect of Decursin and Decursinol Angelate from Angelica gigas Nakai. Yakhak Hoeji. 53: 303-313.
  39. Suh, G. H., M. Knapp, and C. J. Kang, 2006. The economic costs of dementia in Korea, Int. J. Geriatr Psychiatry, 21: 722-728. https://doi.org/10.1002/gps.1552
  40. Sung S. H., S. Y. Kang, K. Y. Lee, M. J. Park, J. H. Kim., J. H. Park, Y. C. Kim, J. Kim, and Y. C. Kim. 2002. (+)-$\alpha$-Viniferin, a Stilbene Trimer from Caragana chamlague, Inhibits Acetylcholinesterase. Biol. Pharm. Bull. 25: 125-127. https://doi.org/10.1248/bpb.25.125
  41. Wang P., H. Yan, and X. Tang. 2006. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacologica Sinica. 27: 1-26. https://doi.org/10.1111/j.1745-7254.2006.00255.x
  42. Watanabe T., N. Yamagata, T. Takasaki, K. Sano, K. Hayakawa, S. Katsurabayashi, N. Egashira, K. Mishima, K. Iwasaki. and M. Fujiwara. 2009. Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease. Brain Res. 1249: 222-228.
  43. Wenk G. L. 2006. Neuropathologic changes in Alzheimer's disease: potential targets for treatment. J. Clin. Psychiatry. 67: 3-7. https://doi.org/10.4088/JCP.0706e03
  44. Wilkinson D. G., P. T. Francis, E. Schwam, and J. Payne-Parrish. 2004. Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 21: 453-478. https://doi.org/10.2165/00002512-200421070-00004
  45. Yoon M. Y., J. Y. Kim, J. H. Hwang, M. R. Cha, M. R. Lee, K. J. Jo, and H. R. Park. 2007. Protective Effect of Methanolic Extracts from Dendrobium nobile Lindl. on H2O2-induced Neurotoxicity in PC12 cells. J. Kor. Soc. Appl. Biol. Chem. 50: 63-67.
  46. Zotova E., J. A. R. Nicoll, K. Ralaria, C. Holmes, and D. Boche. 2010. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy. Alzheimer's Res. Therapy. 2: 1-9. https://doi.org/10.1186/alzrt24