Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiol...Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiologic hallmarks, such as amyloid β （Aβ）, phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD.展开更多
Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for i...Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.展开更多
Neuroinflammation has always been of concern in the pathogenesis of Alzheimer’s disease （AD）. As a major inflammatory mediator, prostaglandin E2 （PGE2） plays an important role in the inflammatory process of AD. U...Neuroinflammation has always been of concern in the pathogenesis of Alzheimer’s disease （AD）. As a major inflammatory mediator, prostaglandin E2 （PGE2） plays an important role in the inflammatory process of AD. Up to now, there is still controversy on the neuroprotective or neurotoxic role of PGE2. However, the role of PGE2 in neurodegeneration may be far more complex, due to the 4 EP receptor subtypes. This article aims to summarize the relationship between PGE2 receptor EP subtypes and AD. It is believed that a better understanding of the PGE2 receptor EP subtypes may help to clarify the relation between inflammation and AD, and to develop novel therapeutic strategies targeting specific EP receptor for AD treatment.展开更多
Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechan...Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.展开更多
Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected accord...Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected according to the pathophysiological causes of AD,including senescence accelerated mouse/prone(SAMP)mice,soluble amyloid-βprotein(Aβ)injection mice/rats,amyloid precursor protein(APP)transgenic mice,and APP/PS1 double transgenic mice.Through the observation of behavioral changes and analysis of core items,the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored.Results:Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction;the major action mechanisms including increasing cerebral blood flow,improving the expressions of vital proteins in the hippocampus,preventing neuron cell apoptosis,promoting the clearance of Aβdeposition,activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor,tyrosine kinase receptor B,N-acetylaspartate and glutamic acid.Conclusion:Although the optimal mouse model is not determined,it is sure that acupuncture-moxibustion therapy can improve cognitive function.A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.展开更多
The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer’s disease(AD) and amnestic mild cognitive impairment(aMCI) based on a triple network mod...The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer’s disease(AD) and amnestic mild cognitive impairment(aMCI) based on a triple network model consisting of the default mode network(DMN), salience network(SN), and executive control network(ECN). The technique of voxel-mirrored homotopic connectivity(VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that:(1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions(i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions(i.e. frontoinsular cortex), and ECN-related brain regions(i.e. frontal middle gyrus and frontal inferior);(2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control(HC) groups, but no significant difference was observed between the a MCI and HC groups; and(3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination(MMSE) and Montreal Cognitive Scale(MOCA) scores and their factor scores in the AD, a MCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the a MCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.展开更多
Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which af...Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine （8-OHdG） in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 ： 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months （ratio 2.37：1）. In contrast, the level of Aβ1-42 in the brain （160.6 ng/mg protein） was higher than that of Aβ1-40 （74 ng/mg protein） （ratio 2.17：1）. In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in producing Aβ1-42 peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. Conclusion These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.展开更多
OBJECTIVE: To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gαq/11expression and Na+-K+-ATPenzymeactivityin rat models of Alzheimer's disease(AD) caused by injecting Aβ25-35 into...OBJECTIVE: To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gαq/11expression and Na+-K+-ATPenzymeactivityin rat models of Alzheimer's disease(AD) caused by injecting Aβ25-35 into the hippocampus.METHODS: Ninety male Wistar rats(age ≥10 months)were selected and injected with Aβ25-35 into their hippocampi to establish model animals,which were randomly divided into six groups including a sham-operated group(blank group), a model group, a donepezil HCL group(Western Medicinegroup),and ahigh/general/dilute concentrations of Yizhitongxuan decoction groups(TCMⅠⅡⅢgroup).The Morris watermaze was used to examine the learning and memory abilities of rats in each group by place navigation and spatial probe tests.Then, the rats were sacrificed to collect the hippocampi for biochemical tests, using western blotting to detect the expression of Gαq/11 and an ultramicro Na+-K+-ATP enzyme kit to measure Na+-K+-ATP enzyme activity.RESULTS:Yizhitongxuan decoction improved model rats' learning and memory abilities, and increased the expression of Gαq/11 in the hippocampus and the level of Na+-K+-ATP enzyme activity in braintissue.CONCLUSION: Yizhitongxuan decoction could improve model rats' learning and memory abilities,and had a regulating effect on the expression of Gαq/11and Na+-K+-ATP enzyme activity.展开更多
OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and cons...OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.展开更多
OBJECTIVE:To observe the effects of Compound Danshen Tablets(CDST) on spatial cognition and expression of brain b-amyloid precursor protein(β-APP) in a rat model of Alzheimer's disease.METHODS:The rat model of Al...OBJECTIVE:To observe the effects of Compound Danshen Tablets(CDST) on spatial cognition and expression of brain b-amyloid precursor protein(β-APP) in a rat model of Alzheimer's disease.METHODS:The rat model of Alzheimer's disease(AD) was established using D-galactose to cause subacute aging combined with Meynert nucleus damage.Rat behavior was monitored using the Morris water maze,and the expression of β-APP in rat brain tissue was detected via immunohistochemistry.RESULTS:CDST significantly improved spatial cognition and decreased β-APP expression in the cortex and hippocampus(P<0.05,P<0.01).CONCLUSIONS:CDST can significantly improve spatial cognition in a rat model of AD.This observation is possibly related to a reduction in β-APP ex-pression in the rat brain.展开更多
文摘Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiologic hallmarks, such as amyloid β （Aβ）, phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD.
基金Acknowledgments The authors thank the National Natural Science Foundation of China （81302646）, Natural Science Foundation of Zhejiang Province （LQ13H300002）, Science Technology Department of Zhejiang Province （2015F50015） and Health and Family Planning commission of Zhejiang Province （XKQ-010-001 and 2013KYB070） for financial support.
文摘Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.
基金supported by grantsfrom the Natural Science Foundation of Zhejiang Province(No. Y206153)the Science and Technology Major Projectsof Zhejiang Province (No. 2007C13053, 2008F80009)the Science and Technology Programme of Hangzhou Munici-pality (No. 20051323B45)
文摘Neuroinflammation has always been of concern in the pathogenesis of Alzheimer’s disease （AD）. As a major inflammatory mediator, prostaglandin E2 （PGE2） plays an important role in the inflammatory process of AD. Up to now, there is still controversy on the neuroprotective or neurotoxic role of PGE2. However, the role of PGE2 in neurodegeneration may be far more complex, due to the 4 EP receptor subtypes. This article aims to summarize the relationship between PGE2 receptor EP subtypes and AD. It is believed that a better understanding of the PGE2 receptor EP subtypes may help to clarify the relation between inflammation and AD, and to develop novel therapeutic strategies targeting specific EP receptor for AD treatment.
基金supported by the National Mega-Project for Drug Research&Development,China(to Jiang Jian Dong)
文摘Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.
文摘Objective:To evaluate the prevention and treatment effects of acupuncture-moxibustion for Alzheimer disease(AD)based on various AD mouse models.Methods:Several representative types of mouse models were selected according to the pathophysiological causes of AD,including senescence accelerated mouse/prone(SAMP)mice,soluble amyloid-βprotein(Aβ)injection mice/rats,amyloid precursor protein(APP)transgenic mice,and APP/PS1 double transgenic mice.Through the observation of behavioral changes and analysis of core items,the possible mechanisms of acupuncture-moxibustion in preventing and treating AD were explored.Results:Acupuncture-moxibusiton therapy can improve AD mice's cognitive dysfunction;the major action mechanisms including increasing cerebral blood flow,improving the expressions of vital proteins in the hippocampus,preventing neuron cell apoptosis,promoting the clearance of Aβdeposition,activating autophagy pathway to reduce memory deficits and regulating the metabolisms of brain-derived neurotrophic factor,tyrosine kinase receptor B,N-acetylaspartate and glutamic acid.Conclusion:Although the optimal mouse model is not determined,it is sure that acupuncture-moxibustion therapy can improve cognitive function.A more suitable AD animal model should be duplicated in order to better explore the inherent action mechanism of acupuncture-moxibustion in preventing and treating AD.
基金Project supported by the National Natural Science Foundation of China(No.81771158)the Science Foundation of the Health Commission of Zhejiang Province(Nos.2016147373 and 2019321345),China
文摘The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer’s disease(AD) and amnestic mild cognitive impairment(aMCI) based on a triple network model consisting of the default mode network(DMN), salience network(SN), and executive control network(ECN). The technique of voxel-mirrored homotopic connectivity(VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that:(1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions(i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions(i.e. frontoinsular cortex), and ECN-related brain regions(i.e. frontal middle gyrus and frontal inferior);(2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control(HC) groups, but no significant difference was observed between the a MCI and HC groups; and(3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination(MMSE) and Montreal Cognitive Scale(MOCA) scores and their factor scores in the AD, a MCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the a MCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.
基金supported by ApoPharma Inc.through a collaborative research project between NRC-IBS and ApoPharma Inc
文摘Objective The double transgenic mouse model （APPswe/PSldE9） of Alzheimer＇s disease （AD） has been widely used in experimental studies. β-Amyloid （Aβ） peptide is excessively produced in AD mouse brain, which affects synaptic function and the development of central nervous system. However, little has been reported on characterization of this model. The present study aimed to characterize this mouse AD model and its wild-type counterparts by biochemical and functional approaches. Methods Blood samples were collected from the transgenic and the wild-type mice, and radial arm water maze behavioral test was conducted at the ages of 6 and 12 months. The mice were sacrificed at 12-month age. One hemisphere of the brain was frozen-sectioned for immunohistochemistry and the other hemisphere was dissected into 7 regions. The levels ofAβ1-40, Aβ1-42 and 8-hydroxydeoxyguanosine （8-OHdG） in blood or/and brain samples were analyzed by ELISA. Secretase activities in brain regions were analyzed by in vitro assays. Results The pre-mature death rate of transgenic mice was approximately 35% before 6-month age, and high levels of Aβ1-40 and Aβ1-42 were detected in these dead mice brains with a ratio of 1 ： 1 0. The level of blood-borne Aβ at 6-month age was similar with that at 12-month age. Besides, Aβ1-40 level in the blood was significantly higher than Aβ1-42 level at the ages of 6 and 12 months （ratio 2.37：1）. In contrast, the level of Aβ1-42 in the brain （160.6 ng/mg protein） was higher than that of Aβ1-40 （74 ng/mg protein） （ratio 2.17：1）. In addition, the levels of Aβ1-40 and Aβ1-42 varied markedly among different brain regions. Aβ1-42 level was significantly higher than Aβ1-40 level in cerebellum, frontal and posterior cortex, and hippocampus. Secretase activity assays did not reveal major differences among different brain regions or between wild-type and transgenic mice, suggesting that the transgene PS1 did not lead to higher 7-secretase activity but was more efficient in producing Aβ1-42 peptides. 8-OHdG, the biomarker of DNA oxidative damage, showed a trend of increase in the blood of transgenic mice, but with no significant difference, as compared with the wild-type mice. Behavioral tests showed that transgenic mice had significant memory deficits at 6-month age compared to wild-type controls, and the deficits were exacerbated at 12-month age with more errors. Conclusion These results suggest that this mouse model mimics the early-onset human AD and may represent full-blown disease at as early as 6-month age for experimental studies.
基金Supported by the Project of Science and Technology in Shandong Universities of Shandong Provincial Education Department(No.J11LF09)
文摘OBJECTIVE: To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gαq/11expression and Na+-K+-ATPenzymeactivityin rat models of Alzheimer's disease(AD) caused by injecting Aβ25-35 into the hippocampus.METHODS: Ninety male Wistar rats(age ≥10 months)were selected and injected with Aβ25-35 into their hippocampi to establish model animals,which were randomly divided into six groups including a sham-operated group(blank group), a model group, a donepezil HCL group(Western Medicinegroup),and ahigh/general/dilute concentrations of Yizhitongxuan decoction groups(TCMⅠⅡⅢgroup).The Morris watermaze was used to examine the learning and memory abilities of rats in each group by place navigation and spatial probe tests.Then, the rats were sacrificed to collect the hippocampi for biochemical tests, using western blotting to detect the expression of Gαq/11 and an ultramicro Na+-K+-ATP enzyme kit to measure Na+-K+-ATP enzyme activity.RESULTS:Yizhitongxuan decoction improved model rats' learning and memory abilities, and increased the expression of Gαq/11 in the hippocampus and the level of Na+-K+-ATP enzyme activity in braintissue.CONCLUSION: Yizhitongxuan decoction could improve model rats' learning and memory abilities,and had a regulating effect on the expression of Gαq/11and Na+-K+-ATP enzyme activity.
基金Supported by the Ministry of Education,Science and Technology (MEST)Korea Institute for Advancement of Technology (KIAT) through the Human Resource Training Project for Regional Innovation
文摘OBJECTIVE： To study the chemical constituents of Zhizi （Fructus Gardeniae） and their antiamnesic ef- fect in a mouse model of Alzheimer＇s disease. METHODS： Ameliorating effects of the extracts, fractions and constituents on scopolamine-in- duced memory impairment in vivo using a passive avoidance task system and their inhibitory activi- ties on acetylcholinesterase （ACHE） in vitro were ex- amined. The isolation of components was per- formed by chromatographic techniques and their structures were identified on the basis of spectral analysis. RESULTS： Activity-guided fractionation of the total extracts resulted in the isolation of two glycosides, geniposide and cr0cin from the n-butanol fraction and genipin and crocetin from the ethylacetate fraction. Among the fractions tested, n-butanol fraction showed the strongest AChE inhibition （43.4% at a final dose of 0.03 mg/mL） and also ex- hibited outstanding efficacy （65.9% at a dose of2.50 mg/kg） in an experimental model of amnesia. Geniposide showed a 22.8% AChE inhibitory activi- ty and a potent ameliorating effect on scopol- amine-induced memory impairment in amnesic mice of 93.4% as compared to the control group. CONCLUSION： Geniposide, a main constituent of gardenia should be considered a candidate for fur- ther clinical study for the purpose of developing a cognition activator and its mechanism of action may be mediated, at least in part, by the acetylcho- line enhancing cholinergic nervous system.
基金Supported by the National Science and Technology "12th Five-years" Major Special-purpose Foundation (No 2011ZX09201-201-01)
文摘OBJECTIVE:To observe the effects of Compound Danshen Tablets(CDST) on spatial cognition and expression of brain b-amyloid precursor protein(β-APP) in a rat model of Alzheimer's disease.METHODS:The rat model of Alzheimer's disease(AD) was established using D-galactose to cause subacute aging combined with Meynert nucleus damage.Rat behavior was monitored using the Morris water maze,and the expression of β-APP in rat brain tissue was detected via immunohistochemistry.RESULTS:CDST significantly improved spatial cognition and decreased β-APP expression in the cortex and hippocampus(P<0.05,P<0.01).CONCLUSIONS:CDST can significantly improve spatial cognition in a rat model of AD.This observation is possibly related to a reduction in β-APP ex-pression in the rat brain.
