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 identi...
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-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) 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 $A{\beta}O$-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 $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, 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 ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.
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-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) 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 $A{\beta}O$-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 $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, 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 ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.
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제안 방법
Acquisition and retention trials of the passive avoidance task were performed at 7 and 8 days, respectively, after AβO injection.
Immediately after AβO injection, the mice were administered spinosin (5, 10, or 20 mg/kg, p.o), and the mice were administered spinosin injections once a day for 6 days.
, 2013). The mice were administered either spinosin (5, 10 or 20 mg/kg, p.o.) or donepezil (5 mg/kg, p.o.) for 6 days, and the last treatment was administered at 24 h before the acquisition trial. The control group received 10% Tween 80 solution at the same volume as used in the experimental groups.
, ABC, CAB, or BCA but not BAB). The mice were administered either spinosin (5, 10 or 20 mg/kg, p.o.) or donepezil (5 mg/kg, p.o.) for 6 days, and the last treatment was administered at 24 h before the test. The control group animals received 10% Tween 80 solution rather than spinosin or donepezil.
대상 데이터
(Carlsbad, CA, USA). Rat polyclonal anti-OX-42 and goat polyclonal antiChAT antibodies were purchased from Chemicon(Temecula, CA, USA). All other materials were of the highest grade commercially available.
Testing was performed in a box comprising of two identical chambers (20×20×20 cm) with one illuminated with 50-W bulb and a non-illuminated chamber separated with a guillotine door (5×5 cm).
데이터처리
The data are expressed as the means ± S.E.M. The latencies in the passive avoidance task, spontaneous alternations in the Y-maze task, and the data from the Western blot and immunohistochemistry experiments were analyzed using oneway analysis of variance (ANOVA) followed by the StudentNewman-Keuls test for multiple comparisons.
이론/모형
The Aβ1-42 oligomer (AβO) was incubated at 4°C for 24 h in the presence or absence of spinosin. Oligomer formation was detected using a Thioflavin T (ThT) fluorescence assay. The data represent the means ± S.
The aliquoted peptides were dissolved in anhydrous DMSO to a final concentration of 1 mM. The protein concentration of the solution was determined using a Bradford assay. Subsequently, the stock was directly diluted into phosphatebuffered saline (PBS, pH 8.
후속연구
Therefore, we proposed that the effects of spinosin reflect the structural specificity of this compound, similar to flavonoid or polyhydroxylated compound. Further studies are needed to determine the precise neuroprotection mechanism of spinosin.
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