Objective To observe the effect of 2,3,5,4'-tetrahydroxy stilbene-2-?-D-glycoside (TSG)on learning and memory and free radicals metabolism in mice with dementia induced by ?-amyloid(A?).Methods The mice models were established by injection of A?1-40 into the right lateral ventricle,and the treatment group was administered with TSG for 8 weeks by gastrogavage.Morris water maze and step-through test were performed in all the mice and then the mice were killed and radioimmunoassay was used to detect the content of interleukin-6(IL-6).Results The learning and memory in model mice were worse and the cortical IL-6 content increased compared to the normal control mice.TSG improved the learning and memory of A?-induced model mice and reduced cortical IL-6 content.Conclusion TSG could improve the learning and memory of dementia mice and decrease cortical IL-6 content,indicating a promising prospect in the treatment of dementia disease such as Alzheimer's disease.

ObjectiveTo observe the effect of 2,3,5,4'-tetrahydroxy stilbene-2-β-D-glycoside(TSG) on learning and memory ability and free radicals metabolism in dementia model mice induced by β-amyloid (Aβ).MethodsAβ1-40 was given to the right lateral ventricle in the model group, and the TSG had been administered to the therapy group for 8 weeks by gastrogavage.All the mice of different groups were tested with Morris water maze and step-through test. Then the mice were killed and biochemical assays of neurol MDA,MAO-B,T-AOC were performed.ResultsThe model mice showed worse ability in learning and memory compared with control mice. The MDA cotent, MAO-B activity in the cortical increased in model mice compared with normal control; TSG reduced the MDA content, MAO-B activity,and increased T-AOC activity.ConclusionTSG can improve the learning and memory ability of model mice, decrease peroxidation level of brain, and increase antioxidation ability of brain, which suggest that TSG may have a promising application in treatment of dementia disease such as AD.

Aim To observe the effect of taurine on learning-memory ability and its mechanism in model mice induced by scopolamine(Scop). Methods Kunming mice were randomly divided into normal control group, Scop model group, taurine groups (0.3, 0.75, 1.875 g?kg -1) and Piracetam group (positive control group). The drugs were continually intra-gastrically administrated for 5 days. On day 5, after intraperitoneal injection of scopolamine, mice were subjected to Morris water maze test. 5 days later, M-cholinregic receptor binding was assayed by radio ligand binding test.Results Compared with model group, significant decrease of swimming time and distance in Morris water maze test was observed in all 3 taurine groups. Taurine at middle dose increased M-cholinergic receptor binding in the brain of model mice. Conclusion Taurine effectively improves learning-memory ability in model mice induced by scopolamine injection. The mechanism relates with the improvement of M-cholinergic receptors of brain.

OBJECTIVE:To investigate the effect of 2,3,5,4'—tetrahydroxystilbene—2—O—?—D—glucoside(TSG) on the learning and memory ability of mouse dementia models induced by scopolamine METHODS:Mice were randomly divided into blank group,model group,TSG groups(low dose,high dose) and positive control(Piracitam) group All the mouse were intragastrically administrated by drugs After making model,all mice were subjected to Morris water maze and passive avoidance tests RESULTS:Compared with model group,swimming time were significantly reduced in the blank group,positive control group and high dose of TSG group during Morris water maze test (P

OBJECTIVE:To observe the effect of2,3,5,4'-tetrahydroxy stilbene—2—?—D—glycoside(TSG)on learning and memory ability and neurotrophic factors of dementle model mice induced by D-galactose.METHODS:The mice were randomly divided into normal control,D-galatose model,VitE positive control,TSG low dose(0.033g/kg),TSG medium dose(0.1g/kg),TSG high dose(0.3g/kg)groups.The mice of various therapy groups excluding the normal Control group were in?jected with D-galactose(D-gal)solution s.c.(50mg/kg/day)over a60-day period,while normal control was injected with saline.At the same time,therapy groups were given TSG and positive control VitE(0.08g/kg)a day,and all therapy groups were administered by intragastrically for60days.Then all mice of different groups were tested with Morris water maze test,and five mice of each group were killed and the expression of nerve growth factor(NGF)and neurotrophin-3(NT-3)was determined with immunohistochemistry method.RESULTS:Injection of D-galactose for2months induced the learning and memory dysfunction of mice,and abated NGF and NT-3expression in hippocampal neurons.TSG improved the learning and memory ability of D-gal model mice,promoted NGF and NT-3expression in hippocampal neurons.CONCLUSION:SG can improve memory ability obviously and may prevent and cure dementia disease such as AD.

BACKGROUND: Chinese herb tuber fleeceflower root can enhance learning and memory ability and anti-cerebral ischemia ability in rats,while 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside,the main effective component of tuber fleeceflower root,has very strong brain-protecting ef fects such as anti-oxidation and anti-aging.OBJECTIVE: To observe the amelioration of learning and memory dis order after administration of 2,3,5,4'-tetrahydroxystilbene-2-O-3-D-glucoside in mice with learning and memory disorder caused by scopolamine.DESIGN: Randomized controlled trial.SETTING: Institute of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences.MATERIALS: The experiment was conducted in the Institute of Pharmacology,Xuanwu Hospital of Capital University of Medical Sciences,be tween February 2000 and May 2000.Totally 50 male Kunming mice were recruited and randomized into 5 groups: normal control group, model group,positive control group, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside 0.03 g/kg group (low-dose group), and 2,3,5,4 '-tetrahydroxystilbene-2-O-β- D-glucoside 0.1 g/kg group(high-dose group).2,3,5,4'-tetrahydroxystil bene-2-O-β-D-glucoside was an effective component extracted from Chinese herb tuber fleeceflower root in the Department of Pharmacology, Xuanwu Hospital of Capital University of Medical Sciences.Piracetam was the positive control drug.Morris water maze and passive avoidance reflex box were made in the Institute of Materia Medica, the Chinese Academy of Medical Sciences.METHODS:Administration was given 5 days before experiment.Tap water was intragastrically grven into the mice in normal group and model group. Piracetam of 0.7 g/(kg.d) was given to the mice in positive control group and 0.03 g/kg of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside was given to small-dose group and 0.1 g/kg to large-dose group for 5 consecutive days.Model establishment started 30 minutes after adminis tration in each group on day 6. The same volume of normal saline was in traperitoneally injected into the mice in normal control group and 1 mg/kg of scopolamine was intraperitoneally injected into mice in the other groups.Morris water maze and passive avoidance tests were carried out 20 minters later.Injection dose of model establishment of Morris water maze was 1 mg/kg and that of passive avoidance test was 10 mg/kg.MAIN OUTCOME MEASURES:① Searching distance and time of mice in Morris water maze in each group.② Latency and entry-times of mice in passive avoidance test in each group.RESULTS:All the 50 mice were recruited in the experiment,and 49 of them entered the result analysis,1 mouse in model group died because of intraperitoneal hemorrhage when scopolamine was injected.① Results of Morris water maze test: Searching time and distance were significantly shortened in large-dose group as compared to those in model group[(77.814± 46.492), (99.319± 38.104)s; (1 370.914± 917.40), (1 808.77± 869.36)cm; P all ＜ 0.05]. ② Results of passive avoidance test: The number of en try times in small-dose group and large-dose group was significantly de creased compared with that in model group [(0.00± 0.00), (0.00± 0.00),(0.8571± 2.267) times, P ＜ 0.01], and the latency had an extended tenden cy [(300± 0.00), (300± 0.00), (269.71± 80.128) s ].CONCLUSION: 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside given to mice with learning and memory disorder induced by scopolamine can shorten the searching time and distance in Morris water maze and reduce the number of mistake-making times in passive avoidance test. It suggests that it has ameliorative effects on learning and memory disorder.

ObjectiveTo evaluate the possible effect of SSY-B2 on reducing the loss of neurons and enhancing the expression of nerve growth factor(NGF).MethodsMale adult SD rats were divided randomly into 6 groups as sham group,model group,positive control agent piracetam group, SSY-B2 low(1.5g crude drug/kg), medium(3g crude drug/kg)and high dosage (6g crude drug/kg)group.Bilateral fornix/fimbria transection was carried out in the rats' septohippocampal pathway and 6 weeks' drug treatment was administered with different doses of SSY-B2 and positive control agent piracetam. After behavioral tests, the numbers of neurons in medial septum and immunoreactive products of NGF in different areas were measured, using Nissle staining and immunohistochemical methods.ResultsThere was neural loss in medial septum after fornix /fimbria transection, but SSY-B2 at each dosage markedly reduced the loss(59.13±22.02,50.60±23.18,63.93±18.35,the number of neurons for three SSY-B2 dosage groups,P<0.005 for all compared with the model group 20.33±14.01).The number of NGF positive cells decreased in model group, but did not show significant statistic difference compared with the sham group (P>0.05) in the medial septum, polymorph layer of dentate gyrus and entorhinal cortex/Subiculum area. In the medial septum, all three dosage enhanced the expression of NGF positive cells(145.1±57.7,161.3±08.2,200.6±58.2,the number of neurons for three SSY-B2 dosage group,P<0.005 for all compared with the model group 50.2±48.6). SSY-B2 at low and medium dosage group also increased the number in both entorhinal cortex/Subiculum and polymorph layer of dentate gyrus.Conclusions SSY-B2 can reduce the loss of neurons in the medial septum, which may be involve in increasing expression of NGF;NGF expression in dentate gyrus, subiculum of hippocampal formation and entorhinal cortex increased by SSY-B2 may play a role in the compensation of these area for learning/memory.

Objective To investigate the deficit of extracellular-signal regulated kinase (ERK)1/2 activation in the different age of Alzheimer's disease (AD)-like animal model and the protective effect of 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside(TSG), which is the main component of Polygonum multiflorum, on ERK activation. Methods A generally accepted animal model of AD - PDAPPV717I transgenic (Tg) mouse was observed from 4 to 16 months old. Tg mice were randomly divided into 3 model groups(4, 10 and 16 months old mice)and TSG treated (at doses 120 and 240 μmol/kg/d) groups. TSG was administered to some Tg mice with an age range 4-10 months. In untreated 10 months old Tg mice, the TSG was administrated to those falling in the age range 10-16 months. For the control group we adopted the same age and background C57BL/6J mice. The ERK1/2 expression and phosphorylation were detected by Western blotting.Results In the 4-month-old PDAPPV717I Tg mice, phosphorylation of ERK1/2 decreased significantly in hippocampus and cortex compared with age matched control. In the 10-month-old Tg mice, decrease of ERK1/2 activation was aggravated in cortex but was less in hippocampus. The treatment of TSG at the doses of 120 and 240 μmol/kg for 6 months (from the age of 4 to 10 months) significantly up-regulated ERK1/2 activation in Tg mice. In the 16-month-old Tg mice, over-activation of ERK1/2 occurred in both hippocampus and cortex. The transgenic mice treated by TSG for 6 months (from the age of 10 months to 16 months) showed significant inhibition of over-activation of ERK1/2. Expression of total ERK1/2 showed no difference among control, Tg model and TSG treated groups.Conclusion PDAPPV717I transgenic mice with an age range from 4 to 16 months revealed the time-dependent deficit of ERK1/2 activation. TSG can bring the down or over activation of ERK1/2 into normal. Because ERK1/2 activation plays the crucial role in cellular signal transduction and learning-memory ability, TSG may have beneficial potential to the prevention and treatment of neurodegenerative diseases like AD.

ObjectiveTo study the effect of SSY-B2 on regeneration of central nervous system of rats with bilateral fornix/fimbria transaction.MethodsMale adult SD rats were divided randomly into 6 groups as sham group,model group, positive control agent piracetam group, SSY-B2 low dosage(1.5g crude drug/kg) group, medium dosage(3g crude drug/kg) group and high dosage(6g crude drug/kg) group.The bilateral fornix/fimbria transection in the rats were carried out. After operation, drugs were fed introgastrically to each group respectively for 6 weeks. The immunoreactive products of growth-associated protein-43(GAP-43 )and chondroitin sulfate proteoglycans(CSPG) in defined areas were measured using immunohistochemical methods. ResultsThere was no difference in number of cells expressing GAP-43 between the model group and sham group (P>0.05),but that in low dosage group increased compared with the model group (P<0.001). The CSPG in parietal lobes after lesion expressed,which was in sham group and model group(sham group and model group respectively, 56.43±59.6,116.36±10.561), and SSY-B2 in low and medium dosage inhibited its expression compared with the model group (P<0.05,P<0.01). Conclusions SSY-B2 can enhance the expression of GAP-43 and inhibit the expression or deposition of CSPG, promote axonal regeneration in the CNS, and thus structural repair and functional restoration in certain degree.

Objective To investigate the effect of Epimedium flavanoids (EF) on neuro-inflammatory reaction in Alzheimer disease (AD) mice model.Methods β-amyloid1-40 (Aβ1-40) was injected to the right lateral ventricle of 2-month-old male ICR mice to induce AD model. Morris water maze and step-through tests were used to measure the learning and memory ability of mice. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in the hippocampus were determined by radioimmunoassay. The expression of glial fibrillary acidic protein (GFAP) positive cells (astrocytes) was detected by immunochemistry staining.Results Compared with the sham-operation group, the learning and memory ability decreased (P<0.05, P<0.01), the concentrations of IL-1β and TNF-α in the hippocampus increased (P<0.01) and the expression of astrocytes in the hippocampus elevated (P<0.05) in Aβ1-40 injection model mice. Intragastric administration of EF (100 and 300 mg/kg) for 3 weeks significantly improved the learning and memory ability (P<0.05, P<0.01), decreased IL-1β and TNF-α concentrations in the hippocampus (P<0.05, P<0.01) and inhibited the expression of astrocytes in the hippocampus (P<0.05), compared with Aβ1-40 injection model mice.Conclusion EF can decrease the inflammatory reaction in the brain of mice induced by Aβ.