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
OBJECTIVE To observe the anti-aging effects of SOD mimic AEOL^(-1)0150 in antisenescence accelerated mouse resistant 1(SAMR1)strain.METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL^(-1)0...OBJECTIVE To observe the anti-aging effects of SOD mimic AEOL^(-1)0150 in antisenescence accelerated mouse resistant 1(SAMR1)strain.METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL^(-1)0150 2 mg·kg-1once a week.Morris water maze,new object recognition,nesting and forced swimming were used to observe the behavioral changes of animals.Lymphocyte subgroups and ROS were measured by Flow cytometry.The cytokines levels were determined by Luminex method.The number of DCX+neurons in brain tissue was observed by immunofluorescence.RESULTS The results showed that AEOL^(-1)0150 could prolong the mean lifespan of SAMR1 mice,but it had no obvious effect on maximal lifespan.What′s more,AEOL^(-1)0150 could significantly improve the spatial learning memory of aged mice,but it could not increase the number of DCX+neurons in the hypothalamic MBH and hippocampal DG regions.Then,we observed the effects of AEOL^(-1)0150 on peripheral blood lymphocyte subgroups and cytokines.We found that AEOL^(-1)0150significantly modulated the lymphocyte subgroups and cytokine release.Especially,AEOL^(-1)0150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-αand IL^(-1)7.CONCLUSION The results indicate that AEOL^(-1)0150 has anti-aging effects,and the effects are closely related to modulating immunity and inhibiting SASP production.展开更多
OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people,could not be prevented,halted,or reversed up till now.A large body of pharmacological study has revealed that Liuwei Dihuang(LW) pos...OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people,could not be prevented,halted,or reversed up till now.A large body of pharmacological study has revealed that Liuwei Dihuang(LW) possesses potential therapeutic effects on AD.LW-AFC is key fractions fromLW.In the present study,we investigated the effect of LW-AFC on AD mouse models.METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain(SAMP8),classic AD animal models,were employed.After the treatment of 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 AlphaLISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 and SAMP8 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 amyloid-β(Αβ) deposition in the brain,and reduced the concentration of Aβ1-42 in the hippo.campus and plasma of APP/PS1 mice.LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal(HPA) and hypothalamic-pituitary-gonadal(HPG) axis,enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice.Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman.tine and donepezil.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network,which supports the use of LW-AFC as a potential agent for AD therapy.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.
基金supported by Chinese Scientific and Technological Major Special Project(2014ZX09J13103-01B-003 and 2014ZX09J15104002)
文摘OBJECTIVE To observe the anti-aging effects of SOD mimic AEOL^(-1)0150 in antisenescence accelerated mouse resistant 1(SAMR1)strain.METHODS The lifespan of SAMR1 mice were observed by subcutaneous injection AEOL^(-1)0150 2 mg·kg-1once a week.Morris water maze,new object recognition,nesting and forced swimming were used to observe the behavioral changes of animals.Lymphocyte subgroups and ROS were measured by Flow cytometry.The cytokines levels were determined by Luminex method.The number of DCX+neurons in brain tissue was observed by immunofluorescence.RESULTS The results showed that AEOL^(-1)0150 could prolong the mean lifespan of SAMR1 mice,but it had no obvious effect on maximal lifespan.What′s more,AEOL^(-1)0150 could significantly improve the spatial learning memory of aged mice,but it could not increase the number of DCX+neurons in the hypothalamic MBH and hippocampal DG regions.Then,we observed the effects of AEOL^(-1)0150 on peripheral blood lymphocyte subgroups and cytokines.We found that AEOL^(-1)0150significantly modulated the lymphocyte subgroups and cytokine release.Especially,AEOL^(-1)0150 can dose-dependently inhibit plasma levels of SASP related inflammatory cytokines TNF-αand IL^(-1)7.CONCLUSION The results indicate that AEOL^(-1)0150 has anti-aging effects,and the effects are closely related to modulating immunity and inhibiting SASP production.
基金supported by National Science and Technology Major Projects Initiative(2013ZX09508104) National Natural Science Foundation of China(81473191)
文摘OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people,could not be prevented,halted,or reversed up till now.A large body of pharmacological study has revealed that Liuwei Dihuang(LW) possesses potential therapeutic effects on AD.LW-AFC is key fractions fromLW.In the present study,we investigated the effect of LW-AFC on AD mouse models.METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain(SAMP8),classic AD animal models,were employed.After the treatment of 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 AlphaLISA assay,respectively.Multiplex bead analysis,a radioimmunoassay,immunochemiluminometry,and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry.RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1 and SAMP8 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 amyloid-β(Αβ) deposition in the brain,and reduced the concentration of Aβ1-42 in the hippo.campus and plasma of APP/PS1 mice.LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal(HPA) and hypothalamic-pituitary-gonadal(HPG) axis,enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice.Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman.tine and donepezil.CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network,which supports the use of LW-AFC as a potential agent for AD therapy.
