ObjectiveTo investigate the effects of Xixintang （XXT）-medicated serum on the amyloid β-protein （Aβ）_25-35-induced polarization of BV-2 microglial cells by a cell experiment and uncover the potential mechanisms of this formula in the prevention and treatment of Alzheimer's disease （AD）， thus providing scientific evidence for the clinical application of XXT. MethodsBV-2 microglial cells were subcultured. The optimal concentrations of XXT-medicated serum and Aβ_25-35 were determined via the cell-counting kit-8 （CCK-8） assay. The cell experiment was carried out with the following groups： blank control， model （Aβ_25-35 at 40 μmol·L^-1）， XXT-medicated serum （Aβ_25-35 at 40 μmol·L^-1 + 10% XXT-medicated serum）， and blank serum （Aβ_25-35 at 40 μmol·L^-1 + 10% blank serum）. After 24 hours of cell incubation， immunofluorescence was used to detect the expression of ionized calcium-binding adaptor molecule 1 （IBA1）， CD16/32， and CD206. Real-time PCR was performed to measure the mRNA levels of CD206， CD163， inducible nitric oxide synthase （iNOS）， and arginase 1 （Arg-1）. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of nerve growth factor （NGF）， iNOS， and Arg-1. The nitric oxide （NO） concentration was determined via the nitrate reductase method. ResultsCompared with the blank control group， the model group showed increased expression of IBA1 and CD16/32 （P<0.01）， decreased expression of CD206 （P<0.05）， upregulation in the mRNA level （P<0.01） and content （P<0.05） of iNOS， downregulation in the mRNA levels of CD206， CD163， and Arg-1 （P<0.05， P<0.01）， lowered levels of Arg-1 and NGF （P<0.05）， and an elevation in the NO level （P<0.05）. Compared with the model group， the XXT-medicated serum group exhibited reduced expression of IBA1 and CD16/32 （P<0.05， P<0.01） and increased expression of CD206 （P<0.01）. Both the content and mRNA level of iNOS were downregulated （P<0.05， P<0.01）， while the mRNA levels of CD206， CD163， and Arg-1 were upregulated （P<0.01） in the XXT-medicated serum group. In addition， the XXT-medicated serum group showed elevated levels of Arg-1 and NGF （P<0.05） and a lowered level of NO （P<0.05）. The blank serum group showed no statistically significant differences in the measured parameters compared with the model group. ConclusionThe XXT-medicated serum can inhibit the polarization toward the M1 phenotype and promote the polarization toward the M2 phenotype， exerting anti-inflammatory and neurotrophic effects.

ObjectiveTo explore the potential mechanism of Xixin Decoction （洗心汤， XD） in treating Alzheimer's disease （AD）. MethodsXD-containing serum was prepared， and the BV-2 microglial cell viability was assessed using the CCK8 assay to determine the optimal intervention concentrations of XD-containing serum and amyloid-beta _25-35 （Aβ_25-35） for subsequent experiments. BV-2 cells were divided into four groups， control group， model group （Aβ_25-35）， XD-containing serum group （Aβ_25-35+ XD-containing serum）， and blank serum group （Aβ_25-35 + blank serum）. After 24 hours of culture， the levels of interleukin-1β（IL-1β）， cyclooxygenase-2 （COX-2）， and arginase-2 （Arg-2） in the supernatent were detected by ELISA. Immunofluorescence staining was performed to detect the protein levels of ionized calcium-binding adaptor molecule 1 （IBA1）， CD86， and CD206. RT-PCR was used to analyze the mRNA expression of IL-1β， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. ResultsThe concentrations of 10% XD-containing serum and 40 μmol·L^-¹ Aβ_25-35 were selected for subsequent experiments. Compared to the control group， the model group showed significantly increased levels of IL-1β and COX-2 in the supernatant， as well as elevated protein expression of IBA1 and CD86 and increased mRNA expression of IL-1β and IL-6， while exhibiting significantly reduced levels of Arg-2 in the supernatant， CD206 protein expression， and IL-10 mRNA expression （P＜0.05 or P＜0.01）. Compared to the model group， the XD-containing serum group showed significant improvement in all these indicators （P＜0.01）， whereas no statistically significant differences were observed in the blank serum group （P＞0.05）. ConclusionXD may regulate microglial activation， inhibit pro-inflammatory factors， and enhance anti-inflammatory factor release， thereby improving neuroimmune inflammation and inhibiting the progression of Alzheimer's disease.

Objective To observe the effects of Xixin Decoction on the blood-brain barrier permeability and the expressions of P-glycoprotein(P-gp),cannabinoid receptor 1(CB1)and cannabinoid receptor 2(CB2)in hippocampal tissue of rapidly aging mice(SAMP8);To explore the possible mechanism of Xixin Decoction in the treatment of Alzheimer disease(AD).Methods Totally 60 SAMP8 mice were randomly divided into model group,probiotics group,and Xixin Decoction high-,medium-and low-dosage groups,with 12 mice in each group,another 12 SAMR1 mice were set as control group.The medicated groups received corresponding drugs by gavage for 10 weeks respectively,while the control group and model group were gavaged with equal volume of distilled water.Morris water maze test was used to detect the learning and memory ability of mice,the blood-brain barrier permeability was detected by Evans blue method,the contents of matrix metalloproteinase 9(MMP9),nuclear factor(NF)-κB and tumor necrosis factor-α(TNF-α)in serum were determined by ELISA,the expressions of P-gp,CB1 and CB2 in hippocampal tissue were detected by Western blot,P-gp expression in hippocampal tissue was detected by immunofluorescence staining.Results Compared with the control group,the learning and memory ability of mice in model group significantly decreased,Evans blue exudation in brain tissue significantly increased,the contents of MMP9,TNF-α and NF-κB in serum significantly increased,the expressions of P-gp and CB2 protein significantly decreased,the expression of CB1 protein significantly increased,with statistical significance(P<0.01,P<0.05).Compared with the model group,the learning and memory ability of mice in Xixin Decoction high-dosage group significantly increased,the Evans blue exudation in brain tissue significantly decreased,the contents of MMP9,TNF-α and NF-κB in serum significantly decreased,the protein expressions of P-gp and CB2 significantly increased,and the protein expression of CB1 significantly decreased,with statistical significance(P<0.01,P<0.05).Conclusion Xixin Decoction can improve the spatial learning and memory ability of AD model mice,and its mechanism is related to regulating the permeability of the blood-brain barrier and related protein expression,and inhibiting neuroinflammation.

ObjectiveTo observe the possible mechanism of Xixin Decoction （洗心汤， XXD） in the prevention and treatment of Alzheimer 's disease（AD）. MethodsFifty rapid aging model mice （SAMP8） were randomly divided into model group， probiotic group， high-， moderate- and low-dose group of XXD， with 10 mice in each group. Another 10 homologous anti-rapid aging mice （SAMR1） were set as control group. After 10 weeks of feeding， the control group and the model group were given 10 ml·kg^-1·d^-1 of distilled water by gavage， while the probiotic group （0.39 g·kg^-1·d^-1）， the high-dose group of XXD （5.08 g·kg^-1·d^-1）， the moderate-dose group of XXD （2.54 g·kg^-1·d^-1）， and the low-dose group of XXD （1.27 g·kg^-1·d^-1） were given corresponding drugs or decoctions by gavage， once a day in all groups. After 10 weeks of intragastric administration， Morris water maze was used to detect the spatial learning and memory ability of mice in each group. HE staining was used to observe the pathological changes of hippocampal CA3 region and colon. The levels of β-amyloid 1-42 （Aβ_1-42）， lipopolysaccharide （LPS）， serum amyloid A （SAA） and acetylcholine （ACH） in hippocampus and colon were detected by ELISA.The diversity of intestinal flora in mouse feces was detected by 16S rRNA sequencing. ResultsCompared to those in the control group， the levels of Aβ_1-42，LPS， SAA increased， while the level of ACH decreased in the model group （P＜0.05 or P＜0.01）. Compared to those in the model group， the escape latency period of the probiotic group was significantly shortened on the 2nd and 5th days， while the escape latency period was shortened， and the residence time in the target platform quadrant increased in the high-dose XXD group during the 2nd to 5th days； the escape latency period was shortened significantly in the moderate-dose XXD group on the 5th day （P＜0.05 or P＜0.01）. Compared to those in the model group， the hippocampal neuron cells in the high- and moderate-dose XXD groups were arranged more closely， with decreased levels of SAA， Aβ_1-42 and LPS， increased ACH level， Simpson and Shannon index （P＜0.05 or P＜0.01）； the arrangement of hippocampal neuron cells in the probiotic group and the low-dose XXD group was relatively loose； the proportions of Bacteroidetes and Prevotella were significantly reduced in the probiotic group and the high-dose XXD group， while that of Firmicutes and Lactobacillus significantly increased （P＜0.05 or P＜0.01）. Compared to those in the probiotic group and the high-dose XXD group， the number of goblet cells in the moderate-dose XXD group decreased， and the number of glands in the low-dose XXD group decreased with atrophy. The high-dose XXD group had decreased Aβ_1-42 level in the hippocampus， increased ACH level in thehippocampus and colon tissue， and decreased SAA in the colon tissue than the moderate- and low-dose XXD groups （P＜0.05 or P＜0.01）； moreover， the SAA level in the hippocampus was significantly higher in the low-dose XXD group than the high- and moderate-dose groups （P＜0.01）. ConclusionXXD can improve the spatial learning and memory ability of SAMP8， reduce the production and deposition of LPS， SAA and Aβ_1-42 in brain and intestine， and increase the content of ACH. The mechanism of its prevention and treatment of AD maybe related to regulating intestinal microecology， affecting flora diversity and improving inflammatory response.

Objective　To explore the applicability and best cut-off value of the Montreal Cognitive Assessment Scale Beijing Version (MoCA-BJ) for mild cognitive impairment (MCI) screening in Xian City.Methods　Community residents over 50 years old in Xiancheng District were enrolled as the research object,a random cluster sampling method was used to sample 1195 community elderly people in Xiancheng District.The subjects were tested for cognitive function with the Mini-mental State Examination (MMSE),and were divided into the normal group and the MCI group according to the diagnostic criteria,and the MoCA-BJ test was performed again.Groups were grouped according to education level,and the receiver operating curve (ROC) of each group was drawn to determine the MoCA-BJ cut-off value corresponding to the maximum Youden index.Results　MMSE and MoCA-BJ scores were significantly correlated,the correlation coefficient was 0.791 P<0.001;the best cut-off values of MoCA-BJ in each group were 19 (illiterate),21 (elementary school),and 25 (junior high school and above).The consistency test Kappa value is 0.686 P<0.001,and the consistency is good.Conclusion　MoCA-BJ can be effectively used in the screening of MCI population in this area.

Objective To discuss the effects and security of memantine and donepezil in the treatment of moderate to severe Alzheimer’s disease(AD). Methods Eighty-six AD patients were randomly divided into two groups, the obser-vation group was treated by memantine and donepezil, while the control group was treated by donepezil. The mini-mental state examination (MMSE), ADAS-cog, ADL, NPI were used to evaluate the clinical effects before and after treatment 24 weeks. Results The scores of ADAS-cog,ADL,NPI and MMSE were great significant(P<0.01) in two groups before and after the treatment, the changes of NPI scores in the observation group were significantly higher than in control group (P<0.05),but the adverse reaction of two groups had no significantly difference(P>0.05). Conclusion Both of the two groups have clinical effect on treatment of AD,but memantine and donepezil is better efficacy than donepezil in NPI, and they are all safe.

OBJECTIVETo study the effects of Xixin decoction (XXD) on O-GlcNAc transferase (OGT) and O-GlcNAc glycosidase in O-GlcNAc glycosylation of tau proteins in the brain of rats with sporadic Alzheimer's disease (SAD) and explore the possible mechanism.

METHODSMale SD rats were randomly divided into sham-operated group, model group, donepezil group, and low-, moderate-, and high-dose XXD groups. After treatment and behavioral test, the rats were sacrificed for detecting the expressions of OGT and O-GlcNAc glycosidase in the brain using immunohistochemistry and Western blotting.

RESULTSXXD significantly enhanced the expressions of OGT in the hippocampus of SAD rats and lowered the expression of O-GlcNAc glycosidase (P<0.05 or 0.01). OGT and O-GlcNAc glycosidase expressions showed no significant differences between the model group and donepezil group (P>0.05).

CONCLUSIONXXD can regulate the expression of OGT and O-GlcNAc glycosidase to enhance O-GlcNAc glycosylation of tau proteins in the hippocampus of SAD rats.

Acetylglucosaminidase ; metabolism ; Alzheimer Disease ; chemically induced ; enzymology ; metabolism ; Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Glycosylation ; Hippocampus ; enzymology ; metabolism ; Male ; N-Acetylglucosaminyltransferases ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; tau Proteins ; metabolism

Objective:To study the effects of Xixin decoction (XXD) on O-GlcNAc transferase (OGT) and O-GlcNAc glycosidase in O-GlcNAc glycosylation of tau proteins in the brain of rats with sporadic Alzheimer's disease (SAD) and explore the possible mechanism. Methods Male SD rats were randomly divided into sham-operated group, model group, donepezil group, and low-, moderate-, and high-dose XXD groups. After treatment and behavioral test, the rats were sacrificed for detecting the expressions of OGT and O-GlcNAc glycosidase in the brain using immunohistochemistry and Western blotting. Results XXD significantly enhanced the expressions of OGT in the hippocampus of SAD rats and lowered the expression of O-GlcNAc glycosidase (P<0.05 or 0.01). OGT and O-GlcNAc glycosidase expressions showed no significant differences between the model group and donepezil group (P>0.05). Conclusion XXD can regulate the expression of OGT and O-GlcNAc glycosidase to enhance O-GlcNAc glycosylation of tau proteins in the hippocampus of SAD rats.

Objective:To study the effects of Xixin decoction (XXD) on O-GlcNAc transferase (OGT) and O-GlcNAc glycosidase in O-GlcNAc glycosylation of tau proteins in the brain of rats with sporadic Alzheimer's disease (SAD) and explore the possible mechanism. Methods Male SD rats were randomly divided into sham-operated group, model group, donepezil group, and low-, moderate-, and high-dose XXD groups. After treatment and behavioral test, the rats were sacrificed for detecting the expressions of OGT and O-GlcNAc glycosidase in the brain using immunohistochemistry and Western blotting. Results XXD significantly enhanced the expressions of OGT in the hippocampus of SAD rats and lowered the expression of O-GlcNAc glycosidase (P<0.05 or 0.01). OGT and O-GlcNAc glycosidase expressions showed no significant differences between the model group and donepezil group (P>0.05). Conclusion XXD can regulate the expression of OGT and O-GlcNAc glycosidase to enhance O-GlcNAc glycosylation of tau proteins in the hippocampus of SAD rats.

To study the effects of Chinese herbal medicine Yinsiwei compound (YSW) on spatial learning and memory ability in rats with sporadic Alzheimer disease (SAD) and the ultrastructural basis of the hippocampal neurons.