Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice

Jung, In Ho; Lee, Hyung Eun; Park, Se Jin; Ahn, Young Je; Kwon, Guyoung; Woo, Ha Young; Lee, So Young; Kim, Ju Sun; Jo, Yeong-Woo; Jang, Dae Sik; Kang, Sam Sik; Ryu, Jong Hoon

doi:10.1016/j.pbb.2014.02.015

Cited by 68 publications

(42 citation statements)

References 38 publications

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“…40) Spinosin also reported to show protective effects in scopolamine or Aβ-induced dementia models. 41,42) Moreover, spinosin facilitated neurogenesis and brain BDNF signaling in the hippocampus. 43) Therefore, these two components could be active components of EZJ regarding the present study.…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

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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“…The maze was constructed of dark opaque polyvinyl plastic, as described elsewhere (Jung et al ., 2014). Mice were initially placed within one arm, and the sequence (e.g., ABC, CAB) and number of arm entries were recorded manually for each mouse over an 8 min period.…”

Section: Methodsmentioning

confidence: 99%

Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

Jeon

Kim

Ryu

et al. 2017

Biomolecules & Therapeutics

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To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems.

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“…Correlation Analysis As shown in Table 6, 5-HT was significantly positively correlated with spinosin, danshensu, 6‴-feruloylspinosin and salvianolic acid B (p < 0.01). According to the literature, spinosin may exert sedative-hypnotic effects by activating 5-HT 1A and γ-aminobutyrate (GABA) receptors, 19,20,43) while salvianolic acid B protects cognitive function through the regulation of 5-HT to inflammatory mediators. 44,45) The sedative effects of 6‴-feruloylspinosin may occur by enhancing the expression of the GABA receptor.…”

Section: Optimization Of the Uhplc-tsq-ms/ms Conditionsmentioning

confidence: 99%

“…[14][15][16] As the one of the main constituents, flavonoids have anxiolytic and sedative effects, 17) and its representative components, spinosin and 6‴-feruloylspinosin, can promote sleep. [18][19][20] Danshen, the minister drug in this formula, is mainly used for promoting blood circulation, removing blood stasis, and as an adjuvant therapy for insomnia and neurasthenia. 21,22) In recent years, the water-soluble phenolic acid components of danshen have attracted increasing attention.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Quantification of Seven Constituents from Zaoren Anshen Prescription and Four Endogenic Components in Rat Plasma by UHPLC-TSQ-MS/MS and the Application of the Correlation Study

Wang

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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A highly rapid and sensitive ultra-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-TSQ-MS/MS) method was developed for the simultaneous determination of 7 constituents from Zaoren Anshen prescription (ZAP) and 4 endogenic components in rat plasma. The proteins in the plasma samples were removed using acetonitrile. The separation of the 11 components was performed on an Alltima C18 column (150 4.6 mm, 5 µm) with acetonitrile and 0.01% formic acid water as the mobile phase. Quantification of the 11 components was performed by multiple reaction monitoring (MRM), and the electrospray ion source polarity was switched between positive and negative modes. The method exhibited good linearity for the 11 components (R 2 > 0.9942). The lower quantitative limit for the 11 components was in the range from 0.90-9.95 ng/mL. The precision was evaluated by intraday and interday assays, with all relative standard deviation (RSD)% values within 14.92%. The relative error of the accuracy ranged from 9.90 to 14.93%. The recovery ranged from 73.94 to 101.06%, and the matrix effects of the 7 components ranged from 80.06 to 105.70%. The developed method was successfully applied for correlation analysis for the simultaneous quantification of the 7 constituents from ZAP and 4 endogenic components in rat plasma after ZAP treatment.

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Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice

Cited by 68 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

Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

Simultaneous Quantification of Seven Constituents from Zaoren Anshen Prescription and Four Endogenic Components in Rat Plasma by UHPLC-TSQ-MS/MS and the Application of the Correlation Study

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