| BackgroundAlzheimer’s disease is the common type of dementia, also a common neurodegeneration disease. With the development of aged society, the incidence of the disease is rising. The date of AD patients is36.6million among the world, which is provided by the AD association; however, the number of the AD patients will reach to100.68million by the middle of21centrury. AD will become the public health problem. So it is urgent to reserch the mechanism and therapy of AD in the wordwide.Acori graminei rhizoma(AGR), a traditional Chinese herb, is frequently employed for treatment of neurological disease, β-asarone, the essential componets of AGR, which has low molecular, and can easily pass through the blood-brain barrier, has proved have neuroprotective effects in vitro and vivo of AD models. We used APPswe/PS1dE9double transgenic animal model in this trial, and based on the entry point of eliminating of β-amyloid protein(A β) and reducing of the receptor for advanced glycation end products (RAGE).ObjectivesTo research the effect of β-asarone, the active substance of acorus grand, on Aβ and RAGE of the cortex, and discuss its effect of anti-apoptosis and neural protection.Methods1.4.5month male double-transgenic mice APPswe/PSldE9mice were divided into model group, β-asarone treated group (low-dose-group, middle-dose group, high-dose group) and donepezi treated group randomly. In addition,12male B6mice with same age and background were used as negative controls.2. All mice were oral administered by the drugs from4.5to7months of age. The negative control group and model group were treated with distilled water, β-asarone treated group with β-asarone by dose of21.2mg/kg per day,42.4mg/kg per day,84.8mg/kg per day, and donepezi group treated with donepezi by dose of2mg/kg per day.3. After2.5-month-treatment, neurons and nisslbodies in the hippocampus were detected by nissl staining,.The amyloid senile plaques in the cortex and hippocampus from mice were detected by thiof lavin T staining. The level of A β1-42in mice brain tissues was measured by Western blotting, immunohistochemical method and Elisa assay. The expression of RAGE, APP, PS1, Bcl2and Bax in mice brain tissue was measured by Western blotting. The enzyme activity of capsase3and capsase9in cortex was detected by enzyme activity assay.Results Experiment1:The effect of β-asarone treatment on neuroprotection of APP/PS1mice(1) Nissl staining reveals, compared with control group, there is a disordered arrangement of model groups of neurons and nissl body disappeared appeartly. While compared with model group, the β-asarone group and and donepezil treated group reveals different degrees of improvement, especially for middle-dose of β-asarone treated group.(2) Compared with control group, the expression of Bcl2/Bax was significantly decreased of model group (P<0.01). Compared with model group, the expression of Bcl2/Bax was upregulated by β-asarone treated group and donepezil treated group(P<0.01).Among β-asarone treated group, the therapeutic effect of middle-dose group is most obvious.(3) Compared with control group, the activation of Caspase3and Caspase9was increased, but the result was not statistically sigificant (P>0.05). Compared with model group, the activation of Caspase3and the activation of Caspase9was reduced by β-asarone group treatment group, but the result was not statistically sigificant(P<0.05) Experiment2:The effect of β-asarone treatment on β-amyloid and Aβ1-42of APP/PS1mice(1) Amyloid senile plaques could hardly be found in the cortex and hippocampus of normal group. While, amyloid senile plaques scattered in cortex and hippocampus of model group apparently (P<0.01). Compared with model group, the β-asarone treated group reduced amyloid senile plaques in cortex and hippocampal significantly (P<0.01), Among β-asarone treated group, middle-treated group lessened the amyloid senile plaques of hippocampal most significantly (P<0.01).(2) Compared with control group,the expression of A β1-42was significantly increased of model group (P<0.01). Compared with model group, the expression of A β1-42was reduced by middle-dose group and high-dose β-asarone treated group (P<0.01),the low-dose-β-asarone treated group only showed a decreasing trend(P>0.05).(3) According to immunohistochemical method,we also observed that compared with control group, the expression of A β1-42was significantly increased of model group in the hippocampus andddd cortex, compared with model group, β-asarone treated group could lessened the expression of A β1-42in hippocampal and cortex.(4) The concentration of Aβ1-42in cortex was detected by Elisa assay. Compared with control group, there is an upward trend of modle group. Compared with modle group, β-asarone treated group showed a decreasing trend (P>0.05). Experiment3:The effect of β-asarone treatment on expression of APP and PS1in the APP/PS1mice.(1) Compared with control group, the expression of APP was significantly increased of model group (P<.05). Compared with model group, there is no difference between the β-asarone treated group and model group, so do donepezil group and model gruop.(2) Compared with control group, the expression of PS1was significantly increased of model group (P<0.05). Compared with model group, the expression of PS1was reduced only by middle-dose-β-asarone group donepezil treated group (P<0.05). Experiment3:The effect of β-asarone on the expression of APP and PS1in the APP/PS1mice.(1) Compared with control group, the expression of APP was significantly increased by model group (P<0.01). Compared with model group, there is no difference between the β-asarone treated group and model group(2)Compared with control group, the expression of PS1was significantly increased of model group (P<0.05). Compared with model group, the expression of PS1was reduced by middle-dose-β-asarone group treated group(P<0.05). Experiment4:The effect of β-asarone on the expression of RAGE in the APP/PS1mice.Compared with control group, the expression of RAGE was significantly increased of model group(P<0.05). Compared with model group, the expression of RAGE was reduced by middle-dose-β-asarone group, high-dose-β-asarone group (P<0.05), espacially for middle-dose group (P<0.05)Conclusion(1) β-asarone could inhibit neuronal apoptosis in the brain of APP/PS1double transgenic mice model(2) The neuroprotective effect of β-asarone may have something to do with it’s effect of reducing amyloid plaques and down-regulating the expression of Aβ1-42in the brain of APP/PS1double transgenic mice model.(3) β-asarone reduce the expression of Aβ1-42may via decreaseing the expression of PS1.(4) β-asarone reduce the expression of Aβ1-42may via attenuating the expression of RAGE-the cell surface receptor of Aβ.(5) β-asarone may control the content of Aβ in the brain from double ways.(6) β-asarone may be a potential drug for the therapy of AD. |
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