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

Lee, Hyung Eun; Lee, So Young; Kim, Ju Sun; Park, Se Jin; Kim, Jong Min; Lee, Young Woo; Jung, Jun Man; Kim, Dong Hyun; Shin, Bum Young; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

doi:10.4062/biomolther.2013.043

Cited by 34 publications

(29 citation statements)

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“…[16][17][18][19][20] Further, numerous brain pathology models have indicated memory-enhancing effects of EZJ. 21,22) These findings demonstrated that EZJ can modulate brain function and may show anti-AD actions. To clear this hypothesis, we examined the action of EZJ on Aβ-induced LTP impairment.…”

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confidence: 77%

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The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

Kwon

Jung

Jing

et al. 2017

Biological & Pharmaceutical Bulletin

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Ziziphus jujuba is a plant, which bears fruits and seeds that are used for medicinal purposes in Traditional oriental medicine. The seed of Zizyphus jujuba var. spinosa (EZJ) has been also traditionally used for psychiatric disorders in Chinese and Korean medicines. Recent findings have indicated that EZJ improves memory impairment, a common symptom of various neurological diseases. However, the effects of EZJ on amyloid β (Aβ) toxicity, which is a main cause of Alzheimer's disease (AD), remain to be elucidated. To illuminate the potential anti-AD effect and mechanism in the mouse hippocampal tissue, we examined the effect of standardized EZJ on Aβ-induced synaptic long-term potentiation (LTP) deficit in the hippocampal tissue. EZJ blocked Aβ-induced LTP deficits in a concentration-dependent manner. Moreover, EZJ increased brain-derived neurotrophic factor (BDNF) level in naïve hippocampal slices. The finding that the blockade of BDNF receptor reduced the effect of EZJ suggests that EZJ ameliorates the Aβ-induced LTP deficit through BDNF/topomyosin receptor kinase B (TrkB) signaling. However, transcription or translation inhibitors failed to block the effect of EZJ, suggesting that BDNF synthesis is not required for the action of EZJ on LTP. Finally, we found that EZJ stimulates plasmin activity. In contrast, plasmin inhibitor blocked the effect of EZJ on the Aβ-induced LTP deficit. Our findings indicate that EZJ ameliorates Aβ-induced LTP deficits through BDNF/TrkB signaling. This phenomenon is induced by a regulatory effect of EZJ on the post-translation modification of BDNF.Key words Zizyphus jujuba var. spinosa; amyloid β (Aβ); long-term potentiation; brain-derived neurotrophic factor (BDNF); plasmin Alzheimer's disease (AD) is a typical neurodegenerative disorder showing progressive memory decline. Learning and memory deficits and the loss of higher cognitive function are observed in the early stage of AD. 1) AD is characterized by the amyloid plaques and neurofibrillary tangles accumulation in the brain. Although the specific initiators of AD still remain unknown, mounting evidence suggests that amyloid β (Aβ) plays an important role in the progress of the AD pathology. Extensive research revealed that soluble Aβ oligomers block hippocampal long-term potentiation (LTP), the cellular model of learning and memory.2,3) These indicated that hippocampal LTP could be a target for developing an anti-AD drug.Brain-derived neurotrophic factor (BDNF) is an endogenous neurotrophin family important for the structural and functional plasticity of the brain. 4,5) In AD patients, BDNF level is decreased in the several brain regions even in pre-clinical stages (very earl time) of AD.6,7) Because BDNF is critical for neuronal survival, neuronal function, synaptic plasticity, and cognition, BDNF deficiency may result from AD pathology.8-10) Recent findings have shown that BDNF has protective effects against the toxic effects of Aβ peptides. 11) Therefore, BDNF and its signaling activators are being investigated for applicat...

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confidence: 77%

“…Extraction was conducted two times with 50% ethanol under reflux (80-85°C) for 3 h. Evaporation was conducted under reduced pressure and the extract was dried using spray dryer (yield, 13.8%). 21) EZJ was standardized with spinosin (molecular weight (MW), 608.55, >0.5%). And the chemical profile of EZJ is presented in supplemental Fig.…”

Section: Methodsmentioning

confidence: 99%

The Seed of Zizyphus jujuba var. spinosa Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

Kwon

Jung

Jing

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Western blot analysis was conducted as described elsewhere. 13) Proteins were transferred onto a polyvinylidene difluoride (PVDF) membrane in trans- fer buffer and further separated at 100 V for 2 h at 4°C. The membrane was incubated for 2 h with blocking solution (5% skim milk) at 4°C, followed by overnight incubation with a primary antibody (pERK, anti-rabbit, 1 : 3000; pGSK-3β, antirabbit, 1 : 3000; ERK, anti-rabbit, 1 : 3000; GSK-3β, anti-goat, 1 : 3000).…”

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confidence: 99%

Amyrin Attenuates Scopolamine-Induced Cognitive Impairment in Mice

Park

Ahn

et al. 2014

Biological & Pharmaceutical Bulletin

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Alzheimer's disease, a neurodegenerative disorder, is characterized by progressive cognitive impairment associated with the disruption of cholinergic neurotransmission. The aim of the present study was to evaluate the effect of α-or β-amyrin, a type of pentacyclic triterpene, on the cognitive impairment induced by scopolamine, a muscarinic acetylcholine receptor antagonist. To measure the abilities of various types of learning and memory, we conducted step-through passive avoidance task. Scopolamine induced deficits in learning and memory processes in mice, which were antagonized by a single administration of α-amyrin (2 or 4 mg/kg) or β-amyrin (4 mg/kg), respectively. Additionally, in vitro analysis revealed that acetylcholinesterase activity was inhibited by β-amyrin, but not by α-amyrin. Furthermore, Western blot analysis revealed that the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK) and phosphorylated glycogen synthase kinase-3β (pGSK-3β) were significantly enhanced by a single administration of α-and β-amyrin in the hippocampus. Finally, the memory ameliorating effects of α-or β-amyrin on the scopolamine-induced cognitive impairments were significantly blocked by ERK inhibitor U0126. The present study suggests that α-and β-amyrin may ameliorate the cognitive impairment induced by hypocholinergic neurotransmission via the activation of ERK as well as GSK-3β signaling.

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“…The acquisition and retention trials of the passive avoidance task were conducted for 2 days, as previously described elsewhere (Lee et al ., ). All tests were performed in a box consisting of two identical chambers (20 × 20 × 20 cm) divided by a guillotine door (5 × 5 cm) between the two chambers.…”

Section: Methodsmentioning

confidence: 97%

Cognitive Ameliorating Effect ofAcanthopanax koreanumAgainst Scopolamine-Induced Memory Impairment in Mice

et al. 2017

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Acanthopanax koreanum Nakai (Araliaceae) is one of the most widely cultivated medicinal plants in Jeju Island, Korea, and the roots and stem bark of A. koreanum have been traditionally used as a tonic agent for general weakness. However, the use of A. koreanum for general weakness observed in the elderly, including those with declined cognitive function, has not been intensively investigated. This study was performed to investigate the effect of the ethanol extract of A. koreanum (EEAK) on cholinergic blockade-induced memory impairment in mice. To evaluate the ameliorating effects of EEAK against scopolamine-induced memory impairment, mice were orally administered EEAK (25, 50, 100, or 200 mg/kg), and several behavioral tasks, including a passive avoidance task, the Y-maze, and a novel object recognition task, were employed. Besides, western blot analysis was conducted to examine whether EEAK affected memory-associated signaling molecules, such as protein kinase B (Akt), Ca /calmodulin-dependent protein kinase II (CaMKII), and cAMP response element-binding protein (CREB). The administration of EEAK (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in the passive avoidance task, the Y-maze, and the novel object recognition task. The phosphorylation levels of both Akt and CaMKII were significantly increased by approximately two-fold compared with the control group because of the administration of EEAK (100 or 200 mg/kg) (p < 0.05). Moreover, the phosphorylation level of CREB was also significantly increased compared with the control group by the administration of EEAK (200 mg/kg) (p < 0.05). The present study suggests that EEAK ameliorates the cognitive dysfunction induced by the cholinergic blockade, in part, via several memory-associated signaling molecules and may hold therapeutic potential against cognitive dysfunction, such as that presented in neurodegenerative diseases, for example, Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.

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

Cited by 34 publications

References 38 publications

The Seed of <i>Zizyphus jujuba</i> var. <i>spinosa</i> Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

The Seed of <i>Zizyphus jujuba</i> var. <i>spinosa</i> Attenuates Alzheimer’s Disease-Associated Hippocampal Synaptic Deficits through BDNF/TrkB Signaling

Amyrin Attenuates Scopolamine-Induced Cognitive Impairment in Mice

Cognitive Ameliorating Effect ofAcanthopanax koreanumAgainst Scopolamine-Induced Memory Impairment in Mice

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