Biomol Ther.
2013 Jul;21(4):299-306.
Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice
- Affiliations
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- 1Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, Republic of Korea. jhryu63@khu.ac.kr
- 2Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul 130-701, Republic of Korea.
- 3Natural Products Research Institute and College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
- 4Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
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.
MeSH Terms
-
Alzheimer Disease
Animals
Blotting, Western
Brain-Derived Neurotrophic Factor
Cyclic AMP Response Element-Binding Protein
Dizocilpine Maleate
Ethanol*
Humans
Male
Maze Learning
Memory
Mice*
Mice, Inbred ICR
Motor Activity
N-Methylaspartate
Neurotransmitter Agents
Phosphorylation
Phosphotransferases
Scopolamine Hydrobromide
Ziziphus*
Brain-Derived Neurotrophic Factor
Cyclic AMP Response Element-Binding Protein
Dizocilpine Maleate
Ethanol
Maze Learning
N-Methylaspartate
Neurotransmitter Agents
Phosphotransferases
Scopolamine Hydrobromide
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