The major pathological changes in Alzheimer＇s disease are beta amyloid deposits and cognitive impairment. Calycosin is a typical phy- toestrogen derived from radix astragali that binds to estrogen receptors to produc...The major pathological changes in Alzheimer＇s disease are beta amyloid deposits and cognitive impairment. Calycosin is a typical phy- toestrogen derived from radix astragali that binds to estrogen receptors to produce estrogen-like effects. Radix astragali Calycosin has been shown to relieve cognitive impairment induced by diabetes mellitus, suggesting calycosin may improve the cognitive function of Alzhei- mer＇s disease patients. The protein kinase C pathway is upstream of the mitogen-activated protein kinase pathway and exerts a neuropro- tective effect by regulating Alzheimer＇s disease-related beta amyloid degradation. We hypothesized that calycosin improves the cognitive function of a transgenic mouse model of Alzheimer＇s disease by activating the protein kinase C pathway. Various doses of calycosin （10, 20 and 40 mg/kg） were intraperitoneally injected into APP/PS1 transgenic mice that model Alzheimer＇s disease. Calycosin diminished hippocampal beta amyloid, Tau protein, interleukin-lbeta, tumor necrosis factor-alpha, acetylcholinesterase and malondialdehyde levels in a dose-dependent manner, and increased acetylcholine and glutathione activities. The administration of a protein kinase C inhibitor, cal- phostin C, abolished the neuroprotective effects of calycosin including improving cognitive ability, and anti-oxidative and anti-inflammato- ry effects. Our data demonstrated that calycosin mitigated oxidative stress and inflammatory responses in the hippocampus of Alzheimer＇s disease model mice by activating the protein kinase C pathway, and thereby improving cognitive function.展开更多
基金supported by the a grant from China Postdoctoral Science Project,No.801161020425the Natural Science Foundation of China,No.8160010172
文摘The major pathological changes in Alzheimer＇s disease are beta amyloid deposits and cognitive impairment. Calycosin is a typical phy- toestrogen derived from radix astragali that binds to estrogen receptors to produce estrogen-like effects. Radix astragali Calycosin has been shown to relieve cognitive impairment induced by diabetes mellitus, suggesting calycosin may improve the cognitive function of Alzhei- mer＇s disease patients. The protein kinase C pathway is upstream of the mitogen-activated protein kinase pathway and exerts a neuropro- tective effect by regulating Alzheimer＇s disease-related beta amyloid degradation. We hypothesized that calycosin improves the cognitive function of a transgenic mouse model of Alzheimer＇s disease by activating the protein kinase C pathway. Various doses of calycosin （10, 20 and 40 mg/kg） were intraperitoneally injected into APP/PS1 transgenic mice that model Alzheimer＇s disease. Calycosin diminished hippocampal beta amyloid, Tau protein, interleukin-lbeta, tumor necrosis factor-alpha, acetylcholinesterase and malondialdehyde levels in a dose-dependent manner, and increased acetylcholine and glutathione activities. The administration of a protein kinase C inhibitor, cal- phostin C, abolished the neuroprotective effects of calycosin including improving cognitive ability, and anti-oxidative and anti-inflammato- ry effects. Our data demonstrated that calycosin mitigated oxidative stress and inflammatory responses in the hippocampus of Alzheimer＇s disease model mice by activating the protein kinase C pathway, and thereby improving cognitive function.
