Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice

  • Kwon, Seung-Hwan (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Ma, Shi-Xun (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Joo, Hyun-Joong (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Seok-Yong (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) ;
  • Jang, Choon-Gon (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University)
  • Received : 2013.09.13
  • Accepted : 2013.11.05
  • Published : 2013.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.

Keywords

References

  1. Alberini, C. M. (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol. Rev. 89, 121-145. https://doi.org/10.1152/physrev.00017.2008
  2. Annunziato, L., Amoroso, S., Pannaccione, A., Cataldi, M., Pignataro, G., D'Alessio, A., Sirabella, R., Secondo, A., Sibaud, L. and Di Renzo, G. F. (2003) Apoptosis induced in neuronal cells by oxidative stress: role played by caspases and intracellular calcium ions. Toxicol. Lett. 139, 125-133. https://doi.org/10.1016/S0378-4274(02)00427-7
  3. Bartus, R. T., Dean, R. L., 3rd, Beer, B. and Lippa, A. S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217, 408-414. https://doi.org/10.1126/science.7046051
  4. Beatty, W. W., Butters, N. and Janowsky, D. S. (1986) Patterns of memory failure after scopolamine treatment: implications for cholinergic hypotheses of dementia. Behav. Neural Biol. 45, 196-211. https://doi.org/10.1016/S0163-1047(86)90772-7
  5. Becker, R., Giacobini, E., Elble, R., McIlhany, M. and Sherman, K. (1988) Potential pharmacotherapy of Alzheimer disease. A comparison of various forms of physostigmine administration. Acta Neurol. Scand. Suppl. 116, 19-32.
  6. Ben-Barak, J. and Dudai, Y. (1980) Scopolamine induces an increase in muscarinic receptor level in rat hippocampus. Brain Res. 193, 309-313. https://doi.org/10.1016/0006-8993(80)90973-7
  7. Bierer, L. M., Haroutunian, V., Gabriel, S., Knott, P. J., Carlin, L. S., Purohit, D. P., Perl, D. P., Schmeidler, J., Kanof, P. and Davis, K. L. (1995) Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits. J. Neurochem. 64, 749-760.
  8. Cheng, D. H. and Tang, X. C. (1998) Comparative studies of huperzine A, E2020, and tacrine on behavior and cholinesterase activities. Pharmacol. Biochem. Behav. 60, 377-386. https://doi.org/10.1016/S0091-3057(97)00601-1
  9. Collerton, D. (1986) Cholinergic function and intellectual decline in Alzheimer's disease. Neuroscience 19, 1-28. https://doi.org/10.1016/0306-4522(86)90002-3
  10. El-Sherbiny, D. A., Khalifa, A. E., Attia, A. S. and Eldenshary Eel, D. (2003) Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Pharmacol. Biochem. Behav. 76, 525-533. https://doi.org/10.1016/j.pbb.2003.09.014
  11. Ellman, G. L., Courtney, K. D., Andres, V., Jr. and Feather-Stone, R. M. (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. Fan, Y., Hu, J., Li, J., Yang, Z., Xin, X., Wang, J., Ding, J. and Geng, M. (2005) Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms. Neurosci. Lett. 374, 222-226. https://doi.org/10.1016/j.neulet.2004.10.063
  13. Francis, P. T., Palmer, A. M., Snape, M. and Wilcock, G. K. (1999) The cholinergic hypothesis of Alzheimer's disease: a review of progress. J. Neurol. Neurosurg. Psychiatry 66, 137-147. https://doi.org/10.1136/jnnp.66.2.137
  14. Jeong, E. J., Lee, K. Y., Kim, S. H., Sung, S. H. and Kim, Y. C. (2008) Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice. Eur. J. Pharmacol. 588, 78-84. https://doi.org/10.1016/j.ejphar.2008.04.015
  15. Jia, Y., Gall, C. M. and Lynch, G. (2010) Presynaptic BDNF promotes postsynaptic longterm potentiation in the dorsal striatum. J. Neurosci. 30, 14440-14445. https://doi.org/10.1523/JNEUROSCI.3310-10.2010
  16. Joseph, J. A., Strain, J. G., Jimenez, N. D. and Fisher, D. (1997) Oxidant injury in PC12 cells--a possible model of calcium "dysregulation" in aging: I. Selectivity of protection against oxidative stress. J. Neurochem. 69, 1252-1258.
  17. Kempermann, G. (2008) The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci. 31, 163-169. https://doi.org/10.1016/j.tins.2008.01.002
  18. Kim, D. H., Hung, T. M., Bae, K. H., Jung, J. W., Lee, S., Yoon, B. H., Cheong, J. H., Ko, K. H. and Ryu, J. H. (2006) Gomisin A improves scopolamine-induced memory impairment in mice. Eur. J. Pharmacol. 542, 129-135. https://doi.org/10.1016/j.ejphar.2006.06.015
  19. Komulainen, P., Pedersen, M., Hanninen, T., Bruunsgaard, H., Lakka, T. A., Kivipelto, M., Hassinen, M., Rauramaa, T. H., Pedersen, B. K. and Rauramaa, R. (2008) BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA Study. Neurobiol. Learn. Mem. 90, 596-603. https://doi.org/10.1016/j.nlm.2008.07.014
  20. Kopelman, M. D. and Corn, T. H. (1988) Cholinergic 'blockade' as a model for cholinergic depletion. A comparison of the memory defi-cits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome. Brain 111 (Pt 5), 1079-1110. https://doi.org/10.1093/brain/111.5.1079
  21. Kwon, S. H., Kim, H. C., Lee, S. Y. and Jang, C. G. (2009) Loganin improves learning and memory impairments induced by scopolamine in mice. Eur. J. Pharmacol. 619, 44-49. https://doi.org/10.1016/j.ejphar.2009.06.062
  22. Kwon, S. H., Kim, M. J., Ma, S. X., You, I. J., Hwang, J. Y., Oh, J. H., Kim, S. Y., Kim, H. C., Lee, S. Y. and Jang, C. G. (2012) Eucommia ulmoides Oliv. Bark. protects against hydrogen peroxide-induced neuronal cell death in SH-SY5Y cells. J. Ethnopharmacol. 142, 337-345. https://doi.org/10.1016/j.jep.2012.04.010
  23. Kwon, S. H., Lee, H. K., Kim, J. A., Hong, S. I., Kim, H. C., Jo, T. H., Park, Y. I., Lee, C. K., Kim, Y. B., Lee, S. Y. and Jang, C. G. (2010) Neuroprotective effects of chlorogenic acid on scopolamineinduced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur. J. Pharmacol. 649, 210-217. https://doi.org/10.1016/j.ejphar.2010.09.001
  24. Kwon, S. H., Lee, H. K., Kim, J. A., Hong, S. I., Kim, S. Y., Jo, T. H., Park, Y. I., Lee, C. K., Kim, Y. B., Lee, S. Y. and Jang, C. G. (2011) Neuroprotective effects of Eucommia ulmoides Oliv. Bark on amyloid beta(25-35)-induced learning and memory impairments in mice. Neurosci. Lett. 487, 123-127. https://doi.org/10.1016/j.neulet.2010.10.042
  25. LeDoux, J. E. (1993) Emotional memory systems in the brain. Behav. Brain Res. 58, 69-79. https://doi.org/10.1016/0166-4328(93)90091-4
  26. Lee, M. K., Cho, S. Y., Kim, D. J., Jang, J. Y., Shin, K. H., Park, S. A., Park, E. M., Lee, J. S., Choi, M. S. and Kim, M. J. (2005) Duzhong (Eucommia ulmoides Oliv.) cortex water extract alters heme biosynthesis and erythrocyte antioxidant defense system in leadadministered rats. J. Med. Food 8, 86-92. https://doi.org/10.1089/jmf.2005.8.86
  27. Lovell, M. A., Ehmann, W. D., Butler, S. M. and Markesbery, W. R. (1995) Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease. Neurology 45, 1594-1601. https://doi.org/10.1212/WNL.45.8.1594
  28. Marcus, D. L., Thomas, C., Rodriguez, C., Simberkoff, K., Tsai, J. S., Strafaci, J. A. and Freedman, M. L. (1998) Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease. Exp. Neurol. 150, 40-44. https://doi.org/10.1006/exnr.1997.6750
  29. Mizuno, M., Yamada, K., Maekawa, N., Saito, K., Seishima, M. and Nabeshima, T. (2002) CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning. Behav. Brain Res. 133, 135-141. https://doi.org/10.1016/S0166-4328(01)00470-3
  30. O'Connell, C., Gallagher, H. C., O'Malley, A., Bourke, M. and Regan, C. M. (2000) CREB phosphorylation coincides with transient synapse formation in the rat hippocampal dentate gyrus following avoidance learning. Neural Plast. 7, 279-289. https://doi.org/10.1155/NP.2000.279
  31. Phillips, H. S., Hains, J. M., Armanini, M., Laramee, G. R., Johnson, S. A. and Winslow, J. W. (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. Neuron 7, 695-702. https://doi.org/10.1016/0896-6273(91)90273-3
  32. Sakurai, T., Kato, T., Mori, K., Takano, E., Watabe, S. and Nabeshima, T. (1998) Nefiracetam elevates extracellular acetylcholine level in the frontal cortex of rats with cerebral cholinergic dysfunctions: an in vivo microdialysis study. Neurosci. Lett. 246, 69-72. https://doi.org/10.1016/S0304-3940(98)00244-4
  33. Selkoe, D. J. (1994) Alzheimer's disease: a central role for amyloid. J. Neuropathol. Exp. Neurol. 53, 438-447. https://doi.org/10.1097/00005072-199409000-00003
  34. Singh, B., Bhat, T. K. and Singh, B. (2003) Potential therapeutic applications of some antinutritional plant secondary metabolites. J. Agric. Food Chem. 51, 5579-5597. https://doi.org/10.1021/jf021150r
  35. Wang, W., Sun, F., An, Y., Ai, H., Zhang, L., Huang, W. and Li, L. (2009) Morroniside protects human neuroblastoma SH-SY5Y cells against hydrogen peroxide-induced cytotoxicity. Eur. J. Pharmacol. 613, 19-23. https://doi.org/10.1016/j.ejphar.2009.04.013
  36. Yamada, K. and Nabeshima, T. (2003) Brain-derived neurotrophic factor/ TrkB signaling in memory processes. J. Pharmacol. Sci. 91, 267-270. https://doi.org/10.1254/jphs.91.267
  37. Yu, S. P., Canzoniero, L. M. and Choi, D. W. (2001) Ion homeostasis and apoptosis. Curr. Opin. Cell Biol. 13, 405-411. https://doi.org/10.1016/S0955-0674(00)00228-3

Cited by

  1. Phytochemicals That Regulate Neurodegenerative Disease by Targeting Neurotrophins: A Comprehensive Review vol.2015, 2015, https://doi.org/10.1155/2015/814068
  2. Precautionary Ellagic Acid Treatment Ameliorates Chronically Administered Scopolamine Induced Alzheimer's Type Memory and Cognitive Dysfunctions in Rats vol.6, pp.5, 2015, https://doi.org/10.5567/pharmacologia.2015.192.212
  3. Effect of systemic high dose enzyme replacement therapy on the improvement of CNS defects in a mouse model of mucopolysaccharidosis type II vol.10, pp.1, 2015, https://doi.org/10.1186/s13023-015-0356-0
  4. Antidepressant Potential of Chlorogenic Acid-Enriched Extract from Eucommia ulmoides Oliver Bark with Neuron Protection and Promotion of Serotonin Release through Enhancing Synapsin I Expression vol.21, pp.3, 2016, https://doi.org/10.3390/molecules21030260
  5. Antiamnesic and Antioxidants Effects of Ferulago angulata Essential Oil Against Scopolamine-Induced Memory Impairment in Laboratory Rats vol.40, pp.9, 2015, https://doi.org/10.1007/s11064-015-1662-6
  6. Lactucopicrin ameliorates oxidative stress mediated by scopolamine-induced neurotoxicity through activation of the NRF2 pathway vol.99, 2016, https://doi.org/10.1016/j.neuint.2016.06.010
  7. Effervescent Granules Prepared UsingEucommia ulmoidesOliv. and Moso Bamboo Leaves: Hypoglycemic Activity in HepG2 Cells vol.2016, 2016, https://doi.org/10.1155/2016/6362094
  8. The Protective Effect of Aucubin from Eucommia ulmoides Against Status Epilepticus by Inducing Autophagy and Inhibiting Necroptosis vol.45, pp.03, 2017, https://doi.org/10.1142/S0192415X17500331
  9. Neuroprotective effects of Eucommia ulmoides Oliv. and its bioactive constituent work via ameliorating the ubiquitin-proteasome system vol.15, pp.1, 2015, https://doi.org/10.1186/s12906-015-0675-7
  10. Deer Bone Extract Prevents Against Scopolamine-Induced Memory Impairment in Mice vol.18, pp.2, 2015, https://doi.org/10.1089/jmf.2014.3187
  11. Involvement of the Nrf2/HO-1 signaling pathway in sulfuretin-induced protection against amyloid beta25–35 neurotoxicity vol.304, 2015, https://doi.org/10.1016/j.neuroscience.2015.07.030
  12. Neuroprotective and Antiamnesic Effects ofMitragyna inermisWilld (Rubiaceae) on Scopolamine-Induced Memory Impairment in Mice vol.2017, 2017, https://doi.org/10.1155/2017/5952897
  13. N-palmitoyl serotonin alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of BDNF and p-CREB in mice vol.242, 2015, https://doi.org/10.1016/j.cbi.2015.09.016
  14. Impairment of opiate-mediated behaviors by the selective TRPV1 antagonist SB366791 2017, https://doi.org/10.1111/adb.12460
  15. Differential metformin dose-dependent effects on cognition in rats: role of Akt vol.233, pp.13, 2016, https://doi.org/10.1007/s00213-016-4301-2
  16. Linalool Ameliorates Memory Loss and Behavioral Impairment Induced by REM-Sleep Deprivation through the Serotonergic Pathway vol.26, pp.4, 2018, https://doi.org/10.4062/biomolther.2018.081
  17. Medicinal plants with acetylcholinesterase inhibitory activity vol.29, pp.5, 2018, https://doi.org/10.1515/revneuro-2017-0054
  18. The phosphodiesterase 5 inhibitor, KJH-1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage vol.175, pp.16, 2018, https://doi.org/10.1111/bph.14377
  19. Comparative Evaluation of Prosopis cineraria (L.) Druce and Its ZnO Nanoparticles on Scopolamine Induced Amnesia vol.9, pp.1663-9812, 2018, https://doi.org/10.3389/fphar.2018.00549
  20. The Memory-Enhancing Effects of Liquiritigenin by Activation of NMDA Receptors and the CREB Signaling Pathway in Mice vol.26, pp.2, 2018, https://doi.org/10.4062/biomolther.2016.284
  21. Cognitive Improving Effects by Highbush Blueberry (Vaccinium crymbosum L.) Vinegar on Scopolamine-Induced Amnesia Mice Model vol.66, pp.1, 2013, https://doi.org/10.1021/acs.jafc.7b03965
  22. 6,7,4′-Trihydroxyisoflavone, a major metabolite of daidzein, improves learning and memory via the cholinergic system and the p-CREB/BDNF signaling pathway in mice vol.826, pp.None, 2018, https://doi.org/10.1016/j.ejphar.2018.02.048
  23. Dynamic Changes in Metabolite Accumulation and the Transcriptome during Leaf Growth and Development in Eucommia ulmoides vol.20, pp.16, 2013, https://doi.org/10.3390/ijms20164030
  24. Prevention of short-term memory impairment by Bryophyllum pinnatum (Lam.) Oken and its effect on acetylcholinesterase changes in CCl4-induced neurotoxicity in rats vol.30, pp.5, 2013, https://doi.org/10.1515/jbcpp-2018-0161
  25. Chlorogenic acid protects PC12 cells against corticosterone-induced neurotoxicity related to inhibition of autophagy and apoptosis vol.20, pp.1, 2013, https://doi.org/10.1186/s40360-019-0336-4
  26. Light exposure during late night attenuates the risk of scopolamine-induced Alzheimer disease in aged rats vol.7, pp.1, 2020, https://doi.org/10.1080/2314808x.2020.1763033
  27. Eucommia Leaf Extract Induces BDNF Production in Rat Hypothalamus and Enhances Lipid Metabolism and Aerobic Glycolysis in Rat Liver vol.13, pp.None, 2020, https://doi.org/10.2174/1874467213666200505094631
  28. Enteromorpha prolifera Extract Improves Memory in Scopolamine-Treated Mice via Downregulating Amyloid-β Expression and Upregulating BDNF/TrkB Pathway vol.9, pp.7, 2013, https://doi.org/10.3390/antiox9070620
  29. Enhanced Healthspan in Caenorhabditis elegans Treated With Extracts From the Traditional Chinese Medicine Plants Cuscuta chinensis Lam. and Eucommia ulmoides Oliv. vol.12, pp.None, 2021, https://doi.org/10.3389/fphar.2021.604435
  30. Comparison of Pinoresinol and its Diglucoside on their ADME Properties and Vasorelaxant Effects on Phenylephrine-Induced Model vol.12, pp.None, 2013, https://doi.org/10.3389/fphar.2021.695530