OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted from Liuwei Dihuang decoction,on treatment of Alzheimer′s disease in mouse models.METHODS The APP/PS1 transgenic mic...OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted from Liuwei Dihuang decoction,on treatment of Alzheimer′s disease in mouse models.METHODS The APP/PS1 transgenic mice and senescence-accelerated mouse prone 8(SAMP8)were administered orally by LW-AFC continuously for 3 months.The behavioral tests were conducted by the novel object recognition(recognition memory task),the Morris water maze(spatial memory test),the shuttle box and step-down tests(active and passive avoidance,associative learning task).The synaptic plasticity was evaluated by long-term potentiation(LTP)experiment in anesthetized mice.The cytokine profiles in serum were assayed by multiplex Luminex assay methods.The hormone levels associated with hypothalamo-pituitary-adrenal(HPA)and hypothalamo-pituitary-gonad(HPG)were measured by radioimmunoassay.The levels of Aβ1-40 and Aβ1-42 were assayed by AlphaLISA technique.RESULTS The administration of LW-AFC significantly improved the behavioral performances in novel object recognition tasks,spatial memory tasks,and associative learning tasks both in APP/PS1 transgenic mice and SAMP8 mice,and the inductions of LTP were also significantly facilitated.Meanwhile,the concentrations of Aβ1-40 and Aβ1-42 in cerebral cortex,hippocampus and serum were decreased in LW-AFC treated groups.The serum concentration of some proinflammatory cytokines,such as IL-1β,IL-2,IL-6,IL-17,IL-23,INF-γ,TNF-α,TNF-β,MCP-1 and MIP-1β were significantly decreased,while the anti-inflammatory cytokines,such as IL-4,IL-10,IL-5 and G-CSF were significantly increased.In addition,LW-AFC could also improved the abnormalities of the corticotropin releasing hormone(CRH)and gonadotropin-releasing hormone(GnRH)levels in hypothalamus,the adrenocorticotropic hormone(ACTH),luteinizing hormone(LH)and follicle stimulating hormone(FSH)levels in pituitary,the corticosterone and testosterone level in serum,respectively.CONCLUSION LW-AFC improves cognitive deficits and synaptic plasticity impairments in AD mouse models,and this may be due to,at least in part,the modulation of neuroimmunomodulation network by LW-AFC,suggesting that LW-AFC might be a promising therapy for AD.展开更多
基金The project supported by the National Science and Technology Ministry(2011ZX09102-101-07,2012ZX09301003-002-001,2012BAI29B07)
文摘OBJECTIVE To investigate the effect of LW-AFC,a new formula of the main active components extracted from Liuwei Dihuang decoction,on treatment of Alzheimer′s disease in mouse models.METHODS The APP/PS1 transgenic mice and senescence-accelerated mouse prone 8(SAMP8)were administered orally by LW-AFC continuously for 3 months.The behavioral tests were conducted by the novel object recognition(recognition memory task),the Morris water maze(spatial memory test),the shuttle box and step-down tests(active and passive avoidance,associative learning task).The synaptic plasticity was evaluated by long-term potentiation(LTP)experiment in anesthetized mice.The cytokine profiles in serum were assayed by multiplex Luminex assay methods.The hormone levels associated with hypothalamo-pituitary-adrenal(HPA)and hypothalamo-pituitary-gonad(HPG)were measured by radioimmunoassay.The levels of Aβ1-40 and Aβ1-42 were assayed by AlphaLISA technique.RESULTS The administration of LW-AFC significantly improved the behavioral performances in novel object recognition tasks,spatial memory tasks,and associative learning tasks both in APP/PS1 transgenic mice and SAMP8 mice,and the inductions of LTP were also significantly facilitated.Meanwhile,the concentrations of Aβ1-40 and Aβ1-42 in cerebral cortex,hippocampus and serum were decreased in LW-AFC treated groups.The serum concentration of some proinflammatory cytokines,such as IL-1β,IL-2,IL-6,IL-17,IL-23,INF-γ,TNF-α,TNF-β,MCP-1 and MIP-1β were significantly decreased,while the anti-inflammatory cytokines,such as IL-4,IL-10,IL-5 and G-CSF were significantly increased.In addition,LW-AFC could also improved the abnormalities of the corticotropin releasing hormone(CRH)and gonadotropin-releasing hormone(GnRH)levels in hypothalamus,the adrenocorticotropic hormone(ACTH),luteinizing hormone(LH)and follicle stimulating hormone(FSH)levels in pituitary,the corticosterone and testosterone level in serum,respectively.CONCLUSION LW-AFC improves cognitive deficits and synaptic plasticity impairments in AD mouse models,and this may be due to,at least in part,the modulation of neuroimmunomodulation network by LW-AFC,suggesting that LW-AFC might be a promising therapy for AD.
