OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mic...OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.展开更多
目的:观察姜黄素对β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PSEN1dE9)双转基因小鼠海马神经元B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和三磷酸腺苷结合盒A1(ATP-binding cassette transporter,ABCA1)...目的:观察姜黄素对β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PSEN1dE9)双转基因小鼠海马神经元B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和三磷酸腺苷结合盒A1(ATP-binding cassette transporter,ABCA1)表达的影响,探讨姜黄素在阿尔茨海默病(Alzheimer’s disease,AD)防治中的机制。方法:将10只6月龄的APPswe/PSEN1dE9双转基因小鼠随机分为对照组和姜黄素饲喂组,每组5只。姜黄素饲喂组每天饲喂500 ppm姜黄素,6个月后采用免疫组化法检测小鼠海马神经元SR-BⅠ和ABCA1表达的变化。结果:与对照组相比,姜黄素饲喂组小鼠海马神经元ABCA1表达明显增加(t=-10.805,P=0.000),但2组小鼠海马神经元中均未见SR-BⅠ表达。结论:姜黄素能提高APPswe/PSEN1dE9双转基因小鼠海马神经元ABCA1的表达,而SR-BⅠ在神经元中未见表达。展开更多
Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed t...Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.展开更多
基金supported by National Science and Technology Major Projects Initiative(2013ZX09508104)National Natural Science Foundation of China(81473191)
文摘OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted fromLiuwei Dihuang decoction,on treatment of Alzheimer disease(AD) in mouse models.METHODS After treatment LW-AFC,mice were cognitively evaluated in behavioral experiments.Neuron loss,amyloid-β(Αβ) deposition,and Αβ level were analyzed using Nissl staining,immunofluorescence,and an Alpha LISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using flow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance.In addition,LW-AFC alleviated the neuron loss in the hippocampus,suppressed Αβ deposition in the brain,and reduced the concentration of Aβ1-42 in the hippocampus and plasma of APP/PS1 mice.LW-AFC treatment also significantly decreased the secretion of corticotropin-releasing hormone and gonadotropin-releasing hormone in the hypothalamus,and adrenocorticotropic hormone,luteinizing hormone,and follicle-stimulating hormone in the pituitary.Moreover,LW-AFC increased CD8+CD28+T cells,and reduced CD4^+CD25^+Foxp3^+T cells in the spleen lymphocytes,down-regulated interleukin(IL)-1β,IL-2,IL-6,IL-23,granulocyte-macrophage colony stimulating factor,and tumor necrosis factor-α and-β,and up-regulated IL-4 and granulocyte colony stimulating factor in the plasma of APP/PS1 mice.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of APP/PS1 transgenic micevia the restoration of the NIM network to a greater extent than either memantineor donepezil,which supports the use of LW-AFC as a potential agent for AD therapy.
文摘目的:观察姜黄素对β-淀粉样前体蛋白swe基因/早老蛋白1dE9基因(APPswe/PSEN1dE9)双转基因小鼠海马神经元B类Ⅰ型清道夫受体(scavenger receptor class B typeⅠ,SR-BⅠ)和三磷酸腺苷结合盒A1(ATP-binding cassette transporter,ABCA1)表达的影响,探讨姜黄素在阿尔茨海默病(Alzheimer’s disease,AD)防治中的机制。方法:将10只6月龄的APPswe/PSEN1dE9双转基因小鼠随机分为对照组和姜黄素饲喂组,每组5只。姜黄素饲喂组每天饲喂500 ppm姜黄素,6个月后采用免疫组化法检测小鼠海马神经元SR-BⅠ和ABCA1表达的变化。结果:与对照组相比,姜黄素饲喂组小鼠海马神经元ABCA1表达明显增加(t=-10.805,P=0.000),但2组小鼠海马神经元中均未见SR-BⅠ表达。结论:姜黄素能提高APPswe/PSEN1dE9双转基因小鼠海马神经元ABCA1的表达,而SR-BⅠ在神经元中未见表达。
基金supported by grants from the National Natural Science Foundation of China(No.81803537)the"Major New Drug Creation"of Major Science and Technology Project(No.2015ZX09101-016)+1 种基金Capital Science and Technology Leading Talent Training Project(No.Z191100006119017)Beijing Hospitals Authority Ascent Plan(No.DFL20190803)。
文摘Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.
