Biomolecules & Therapeutics

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

DOI QR Code

Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice

  • Lee, Hyung Eun (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Lee, So Young (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Kim, Ju Sun (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Park, Se Jin (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Kim, Jong Min (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Lee, Young Woo (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Jung, Jun Man (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Kim, Dong Hyun (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Shin, Bum Young (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Jang, Dae Sik (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Kang, Sam Sik (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Ryu, Jong Hoon (Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University)
  • Received : 2013.05.15
  • Accepted : 2013.07.22
  • Published : 2013.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

Keywords

References

  1. Barnes, C. A., Danysz, W. and Parsons, C. G. (1996) Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats. Eur. J. Neurosci. 8, 565-571. https://doi.org/10.1111/j.1460-9568.1996.tb01241.x
  2. Birks, J. S., Melzer, D. and Beppu, H. (2000) Donepezil for mild and moderate Alzheimer's disease. Cochrane Database Syst. Rev. CD001190.
  3. Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi , D., Schutz, G. and Silva, A. J. (1994) Defi cient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59-68. https://doi.org/10.1016/0092-8674(94)90400-6
  4. Cao, J. X., Zhang, Q. Y., Cui, S. Y., Cui, X. Y., Zhang, J., Zhang, Y. H., Bai, Y. J. and Zhao, Y. Y. (2010) Hypnotic effect of jujubosides from Semen Ziziphi Spinosae. J. Ethnopharmacol. 130, 163-166. https://doi.org/10.1016/j.jep.2010.03.023
  5. Chen, C. Y., Chen, Y. F. and Tsai, H. Y. (2008) What is the effective component in suanzaoren decoction for curing insomnia? Discovery by virtual screening and molecular dynamic simulation. J. Biomol. Struct. Dyn. 26, 57-64. https://doi.org/10.1080/07391102.2008.10507223
  6. Daulatzai, M. A. (2010) Early stages of pathogenesis in memory impairment during normal senescence and Alzheimer's disease. J. Alzheimers Dis. 20, 355-367. https://doi.org/10.3233/JAD-2010-1374
  7. Davis, S., Vanhoutte, P., Pages, C., Caboche, J. and Laroche, S. (2000) The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiationdependent gene expression in the dentate gyrus in vivo. J. Neurosci. 20, 4563-4572.
  8. English, J. D. and Sweatt, J. D. (1996) Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J. Biol. Chem. 271, 24329-24332. https://doi.org/10.1074/jbc.271.40.24329
  9. English, J. D. and Sweatt, J. D. (1997) A requirement for the mitogenactivated protein kinase cascade in hippocampal long term potentiation. J. Biol. Chem. 272, 19103-19106. https://doi.org/10.1074/jbc.272.31.19103
  10. Farlow, M., Veloso, F., Moline, M., Yardley, J., Brand-Schieber, E., Bibbiani, F., Zou, H., Hsu, T. and Satlin, A. (2011) Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's disease. BMC Neurol. 11, 57. https://doi.org/10.1186/1471-2377-11-57
  11. Gray, R., Rajan, A. S., Radcliffe, K. A., Yakehiro, M. and Dani, J. A. (1996) Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature 383, 713-716. https://doi.org/10.1038/383713a0
  12. Guil-Guerrero, J. L., Diaz Delgado, A., Matallana Gonzalez, M. C. and Torija Isasa, M. E. (2004) Fatty acids and carotenes in some ber (Ziziphus jujuba Mill) varieties. Plant Foods Hum. Nutr. 59, 23-27. https://doi.org/10.1007/s11130-004-0017-2
  13. Ikarashi, Y., Yuzurihara, M., Takahashi, A., Ishimaru, H., Shiobara, T. and Maruyama, Y. (1998) Direct regulation of acetylcholine release by N-methyl-D-aspartic acid receptors in rat striatum. Brain Res. 795, 215-220. https://doi.org/10.1016/S0006-8993(98)00293-5
  14. Jerusalinsky, D., Kornisiuk, E. and Izquierdo, I. (1997) Cholinergic neurotransmission and synaptic plasticity concerning memory processing. Neurochem. Res. 22, 507-515. https://doi.org/10.1023/A:1027376230898
  15. Jung, J. W., Ahn, N. Y., Oh, H. R., Lee, B. K., Lee, K. J., Kim, S. Y., Cheong, J. H. and Ryu, J. H. (2006) Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla. J. Ethnopharmacol. 108,193-197. https://doi.org/10.1016/j.jep.2006.05.019
  16. 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
  17. Kim, D. H., Jung, H. A., Park, S. J., Kim, J. M., Lee, S., Choi, J. S., Cheong, J. H., Ko, K. H. and Ryu, J. H. (2010) The effects of daidzin and its aglycon, daidzein, on the scopolamine-induced memory impairment in male mice. Arch. Pharm. Res. 33, 1685-1690. https://doi.org/10.1007/s12272-010-1019-2
  18. Knauber, J., Kischka, U., Roth, M., Schmidt, W. J., Hennerici, M. and Fassbender, K. (1999) Modulation of striatal acetylcholine concentrations by NMDA and the competitive NMDA receptor-antagonist AP-5: an in vivo microdialysis study. J. Neural. Transm. 106, 35-45. https://doi.org/10.1007/s007020050139
  19. Morris, R. (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11, 47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  20. Myhrer, T., Danscher, G. and Fonnum, F. (2003) Degenerative patterns following denervation of temporal structures in a rat model of mnemonic dysfunction. Brain Res. 967, 293-300. https://doi.org/10.1016/S0006-8993(03)02232-7
  21. Navakkode, S. and Korte, M. (2012) Cooperation between cholinergic and glutamatergic receptors are essential to induce BDNF-dependent long-lasting memory storage. Hippocampus 22, 335-346. https://doi.org/10.1002/hipo.20902
  22. Palencia, C. A. and Ragozzino, M. E. (2006) The effect of N-methyl-D-aspartate receptor blockade on acetylcholine effl ux in the dorsomedial striatum during response reversal learning. Neuroscience 143, 671-678. https://doi.org/10.1016/j.neuroscience.2006.08.024
  23. Park, J. H., Lee, H. J., Koh, S. B., Ban, J. Y. and Seong, Y. H. (2004) Protection of NMDA-induced neuronal cell damage by methanol extract of Zizyphi Spinosi Semen in cultured rat cerebellar granule cells. J. Ethnopharmacol. 95, 39-45. https://doi.org/10.1016/j.jep.2004.06.011
  24. Park, S. J., Kim, D. H., Jung, J. M., Kim, J. M., Cai, M., Liu, X., Hong, J. G., Lee, C. H., Lee, K. R. and Ryu, J. H. (2012) The ameliorating effects of stigmasterol on scopolamine-induced memory impairments in mice. Eur. J. Pharmacol. 676, 64-70. https://doi.org/10.1016/j.ejphar.2011.11.050
  25. Park, S. J., Kim, D. H., Lee, I. K., Jung, W. Y., Park, D. H., Kim, J. M., Lee, K. R., Lee, K. T., Shin, C. Y., Cheong, J. H., Ko, K. H. and Ryu, J. H. (2010) The ameliorating effect of the extract of the fl ower of Prunella vulgaris var. lilacina on drug-induced memory impairments in mice. Food Chem. Toxicol. 48, 1671-1676. https://doi.org/10.1016/j.fct.2010.03.042
  26. Polster, M. R. (1993) Drug-induced amnesia: implications for cognitive neuropsychological investigations of memory. Psychol. Bull. 114, 477-493. https://doi.org/10.1037/0033-2909.114.3.477
  27. Potter, D. D., Pickles, C. D., Roberts, R. C. and Rugg, M. D. (2000) Scopolamine impairs memory performance and reduces frontal but not parietal visual P3 amplitude. Biol. Psychol. 52, 37-52. https://doi.org/10.1016/S0301-0511(99)00023-X
  28. Sarter, M., Bodewitz, G. and Stephens, D. N. (1988) Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist betacarbolines. Psychopharmacology (Berl) 94, 491-495. https://doi.org/10.1007/BF00212843
  29. Schliebs, R. and Arendt, T. (2011) The cholinergic system in aging and neuronal degeneration. Behav. Brain Res. 221, 555-563. https://doi.org/10.1016/j.bbr.2010.11.058
  30. Shimohama, S., Akaike, A. and Kimura, J. (1996) Nicotine-induced protection against glutamate cytotoxicity. Nicotinic cholinergic receptor-mediated inhibition of nitric oxide formation. Ann. N. Y. Acad. Sci. 777, 356-361. https://doi.org/10.1111/j.1749-6632.1996.tb34445.x
  31. Shintani, E. Y. and Uchida, K. M. (1997) Donepezil: an anticholinesterase inhibitor for Alzheimer's disease. Am. J. Health Syst. Pharm. 54, 2805-2810.
  32. Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J. and Greenberg, M. E. (1998) $Ca^{2+}$ infl ux regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20, 709-726. https://doi.org/10.1016/S0896-6273(00)81010-7
  33. Timofeeva, O. A. and Levin, E. D. (2001) Glutamate and nicotinic receptor interactions in working memory: importance for the cognitive impairment of schizophrenia. Neuroscience 195, 25-36.
  34. Tully, T., Bourtchouladze, R., Scott, R. and Tallman, J. (2003) Targeting the CREB pathway for memory enhancers. Nat. Rev. Drug Discov. 2, 267-277. https://doi.org/10.1038/nrd1061
  35. Xu, Y., Lv, X. F., Cui, C. L., Ge, F. F., Li, Y. J. and Zhang, H. L. (2012) Essential role of NR2B-containing NMDA receptor-ERK pathway in nucleus accumbens shell in morphine-associated contextual memory. Brain Res. Bull. 89, 22-30. https://doi.org/10.1016/j.brainresbull.2012.06.012
  36. You, Z. L., Xia, Q., Liang, F. R., Tang, Y. J., Xu, C. L., Huang, J., Zhao, L., Zhang, W. Z. and He, J. J. (2010) Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons. J. Ethnopharmacol. 128, 419-423. https://doi.org/10.1016/j.jep.2010.01.034
  37. Zhao, J., Li, S. P., Yang, F. Q., Li, P. and Wang, Y. T. (2006) Simultaneous determination of saponins and fatty acids in Ziziphus jujuba (Suanzaoren) by high performance liquid chromatography-evaporative light scattering detection and pressurized liquid extraction. J. Chromatogr. A 1108, 188-194. https://doi.org/10.1016/j.chroma.2005.12.104
  38. Zhou, X., Moon, C., Zheng, F., Luo, Y., Soellner, D., Nunez, J. L. and Wang, H. (2009) N-methyl-D-aspartate-stimulated ERK1/2 signaling and the transcriptional up-regulation of plasticity-related genes are developmentally regulated following in vitro neuronal maturation. J. Neurosci. Res. 87, 2632-2644. https://doi.org/10.1002/jnr.22103
  39. Zheng, F., Zhou, X., Moon, C. and Wang, H. (2012) Regulation of brain-derived neurotrophic factor expression in neurons. Int. J. Physiol. Pathophysiol. Pharmacol. 4, 188-200.

Cited by

  1. Brain-Derived Neurotrophic Factor in Alzheimer’s Disease: Risk, Mechanisms, and Therapy vol.52, pp.3, 2015, https://doi.org/10.1007/s12035-014-8958-4
  2. Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property vol.306, 2016, https://doi.org/10.1016/j.bbr.2016.03.030
  3. Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice vol.25, pp.3, 2017, https://doi.org/10.4062/biomolther.2016.058
  4. Spicatoside A enhances memory consolidation through the brain-derived neurotrophic factor in mice vol.572, 2014, https://doi.org/10.1016/j.neulet.2014.04.034
  5. Pretreatment with 5-hydroxymethyl-2-furaldehyde blocks scopolamine-induced learning deficit in contextual and spatial memory in male mice vol.134, 2015, https://doi.org/10.1016/j.pbb.2015.04.007
  6. Cognitive Ameliorating Effect ofAcanthopanax koreanumAgainst Scopolamine-Induced Memory Impairment in Mice vol.31, pp.3, 2017, https://doi.org/10.1002/ptr.5764
  7. Effects of allantoin on cognitive function and hippocampal neurogenesis vol.64, 2014, https://doi.org/10.1016/j.fct.2013.11.033
  8. The memory-enhancing effect of erucic acid on scopolamine-induced cognitive impairment in mice vol.142, 2016, https://doi.org/10.1016/j.pbb.2016.01.006
  9. Combination Tendency Analysis on Herbal Formula to Treat Insomnia Focused on Zizyphi spinosi Semen vol.22, pp.1, 2014, https://doi.org/10.14374/HFS.2014.22.1.033
  10. Nesfatin-1, a potent anorexic agent, decreases exploration and induces anxiety-like behavior in rats without altering learning or memory vol.1629, 2015, https://doi.org/10.1016/j.brainres.2015.10.027
  11. Oleanolic acid ameliorates cognitive dysfunction caused by cholinergic blockade via TrkB-dependent BDNF signaling vol.113, 2017, https://doi.org/10.1016/j.neuropharm.2016.07.029
  12. The pharmacokinetics and tissue distribution of coumaroylspinosin in rat: A novel flavone C-glycoside derived from Zizyphi Spinosi Semen vol.1046, 2017, https://doi.org/10.1016/j.jchromb.2017.01.030
  13. Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways vol.200, 2017, https://doi.org/10.1016/j.jep.2017.02.009
  14. Artemisia capillaris Thunberg Produces Sedative-Hypnotic Effects in Mice, Which are Probably Mediated Through Potentiation of the GABAA Receptor vol.43, pp.04, 2015, https://doi.org/10.1142/S0192415X1550041X
  15. 4-Hydroxybenzyl methyl ether improves learning and memory in mice via the activation of dopamine D1 receptor signaling vol.121, 2015, https://doi.org/10.1016/j.nlm.2015.03.004
  16. Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice vol.5, pp.1, 2015, https://doi.org/10.1038/srep08502
  17. Oleanolic acid attenuates MK-801-induced schizophrenia-like behaviors in mice vol.86, 2014, https://doi.org/10.1016/j.neuropharm.2014.06.025
  18. The memory ameliorating effects of DHP1402, an herbal mixture, on cholinergic blockade-induced cognitive dysfunction in mice 2017, https://doi.org/10.1016/j.jep.2017.09.013
  19. The protective effect of fermented Curcuma longa L. on memory dysfunction in oxidative stress-induced C6 gliomal cells, proinflammatory-activated BV2 microglial cells, and scopolamine-induced amnesia model in mice vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1880-3
  20. Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice vol.120, 2014, https://doi.org/10.1016/j.pbb.2014.02.015
  21. Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1–42 Oligomer-Induced Memory Impairment in Mice vol.23, pp.2, 2015, https://doi.org/10.4062/biomolther.2014.110
  22. The effects of P2X7 receptor knockout on emotional conditions over the lifespan of mice vol.29, pp.17, 2018, https://doi.org/10.1097/WNR.0000000000001136
  23. GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1 vol.11, pp.1662-5099, 2018, https://doi.org/10.3389/fnmol.2018.00121
  24. Amyrin Attenuates Scopolamine-Induced Cognitive Impairment in Mice vol.37, pp.7, 2014, https://doi.org/10.1248/bpb.b14-00113
  25. The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling vol.40, pp.12, 2013, https://doi.org/10.1248/bpb.b17-00378
  26. Botanical and Traditional Uses and Phytochemical, Pharmacological, Pharmacokinetic, and Toxicological Characteristics of Ziziphi Spinosae Semen : A Review vol.2020, pp.None, 2013, https://doi.org/10.1155/2020/5861821
  27. Antiamnesic and Neuroprotective Effects of an Aqueous Extract of Ziziphus jujuba Mill. (Rhamnaceae) on Scopolamine-Induced Cognitive Impairments in Rats vol.2021, pp.None, 2013, https://doi.org/10.1155/2021/5577163
  28. Ziziphus jujuba (Rhamnaceae) Alleviates Working Memory Impairment and Restores Neurochemical Alterations in the Prefrontal Cortex of D-Galactose-Treated Rats vol.2021, pp.None, 2013, https://doi.org/10.1155/2021/6610864
  29. Kihito prevents corticosterone-induced brain dysfunctions in mice vol.11, pp.6, 2013, https://doi.org/10.1016/j.jtcme.2021.05.002