| In vitro: |
| Biomol Ther (Seoul) . 2019 Jan 1;27(1):71-77. | | Neuroprotective Effects of Spinosin on Recovery of Learning and Memory in a Mouse Model of Alzheimer's Disease[Pubmed: 29925225] | | Abstract
Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by Aβ₁₋₄₂ and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 μg/kg/day), the cognitive impairment of mice induced by Aβ₁₋₄₂ was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aβ₁₋₄₂ accumulation in hippocampus. Aβ₁₋₄₂ induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression, suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.
Keywords: Alzheimer’s disease; Neuroprotection; Semen Ziziphi spinosae; Spinosin. |
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| In vivo: |
| Biomol Ther (Seoul). 2015 Mar;23(2):156-64. | | Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1-42 Oligomer-Induced Memory Impairment in Mice.[Pubmed: 25767684] | Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-β1-42 oligomer (AβO) in mice.
METHODS AND RESULTS:
Memory impairment was induced by intracerebroventricular injection of AβO (50 μM) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated AβO-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through AβO, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after AβO injection. In addition, spinosin rescued the AβO-induced decrease in choline acetyltransferase expression levels.
CONCLUSIONS:
These results suggest that spinosin ameliorated memory impairment induced through AβO, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid b protein-induced cognitive dysfunction observed in AD patients. | | Pharmacol Biochem Behav. 2014 May;120:88-94. | | Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice.[Pubmed: 24582850] | Spinosin is a C-glycoside flavonoid isolated from the seeds of Zizyphus jujuba var. spinosa.
METHODS AND RESULTS:
This study investigated the effect of spinosin on cholinergic blockade-induced memory impairment in mice. Behavioral tests were conducted using the passive avoidance, Y-maze, and Morris water maze tasks to evaluate the memory-ameliorating effect of spinosin. Spinosin (10 or 20mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in these behavioral tasks with a prolonged latency time in the passive avoidance task, an increased percentage of spontaneous alternation in the Y-maze task and a lengthened swimming time in target quadrant in the Morris water maze task. In addition, a single administration of spinosin in normal naïve mice also enhanced the latency time in the passive avoidance task. To identify the mechanism of the memory-ameliorating effect of spinosin, receptor antagonism analysis and Western blotting were performed. The ameliorating effect of spinosin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose (0.5mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)tetralin, a 5-HT1A receptor agonist. In addition, spinosin significantly increased the expression levels of phosphorylated extracellular signal-regulated kinases and cAMP response element-binding proteins in the hippocampus.
CONCLUSIONS:
Taken together, these results indicate that the memory-ameliorating effect of spinosin may be, in part, due to the serotonergic neurotransmitter system, and that spinosin may be useful for the treatment of cognitive dysfunction in diseases such as Alzheimer's disease. |
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