ObjectiveTo observe the effects of Jintong capsule on model rats of Tourette syndrome (TS) and explore its probable pharmacological mechanisms.MethodsSD rats were randomly divided into six groups: blank control, TS model, haloperidol and three Jintong capsule treated groups. Model rats were copied by intraperitoneal injection of iminodipropionitrile (IDPN). The stereotyped behaviors of model rats were recorded. Open field test was used to detect ability of space recognition of rats, high performance liquid chromatography was used to detect content of monoamines, and flow cytometry was used to detect the ratio of T lymphocyte.ResultsJintong capsule can ameliorate the stereotyped behaviors of model rats, decrease content of dopamine in striatum and increase the ratio of CD4/CD8.ConclusionJintong capsule can improve behaviors of model rats. The potential mechanism of Jintong capsule maybe: it can affect the dopaminergic system of model rats, and Jintong can enhance the immune system of model rats.

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.

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.

OBJECTIVE: To study the tongue tissue blood oxygen saturation measurement for evaluating tongue manifestation of blood stasis syndrome, and to explore its correlation with blood rheological disorder in a rat model of acute transient brain ischemia. METHODS: Twenty-eight SD rats were randomly divided into sham-operated group and ischemia group. Middle cerebral artery occlusion was induced by thread in rats of the ischemia group. Tongue tissue blood oxygen saturation, neurological severity score and the changes of blood viscosity, red blood cell deformity, thrombin time and fibrinogen in the rats were measured after 24-hour reperfusion. RESULTS: Blood viscosity and the content of fibrinogen in the ischemia group were significantly higher than those in the sham-operated group. Red blood cell deformity, thrombin time and tongue tissue blood oxygen saturation in the ischemia group were decreased as compared with the sham-operated group. There was a positive correlation between red blood cell deformity and tongue tissue blood oxygen saturation. CONCLUSION: Tongue tissue blood oxygen saturation is a good measurement for evaluating blood stasis in a rat model of focal cerebral ischemia, and this model can be used as a rat model of stroke with blood stasis syndrome.

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 develop three animal models to mimic muscle tremors of Parkinson's disease and observe effects of Chinese herb compounds Jian-Xing on these models.MethodsPure muscle tremor mice models were developed by single intraperitoneal injection of arecoline or oxotremorine. The mitochondria damaged model was developed by intraperitoneal injection of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) 20mg/kg for 8 days. Duration time of tremoring was recorded. The climbing time and spontaneous movements of MPTP mice were recorded. HPLC was used to detect the content of dopamine and it's metabolites in MPTP mice.ResultsAfter injection of oxotremorine or arecoline,model mice exhibited significant tremoring, duration time of tremor of mice in Jian-Xing group shortened significantly. As to MPTP model mice, climbing time of model mice prolonged, times of spontaneous movements of model mice decreased and the content of dopamine in striaturn decreased compared with control group. Climbing time of mice in Jian-Xing group shortened, spontaneous movements increased and content of dopamine increased distinctively. ConclusionOxotremorine, arecoline and MPTP all can produce tremor animal models. Chinese herb compounds Jian-Xing can shorten the duration time of tremor.As to MPTP model, Jian-Xing can shorten the climbing time of model mice, increase the spontaneous movements and increase the content of dopamine in striaturn.

Aim To investigate the effects of ginsenoside(GS) on phosphorylation of tau protein,microtubule,cellular apoptosis and its related factors in cellular model of Alzheimer disease(AD) induced by the protein phosphatase 1 and 2A inhibitor okadaic acid(OA).Methods The human neuroblastoma cell line SK-N-SH cells were cultured with GS for 24 h,the culture medium was changed,and then incubated with OA 10 nmol?L-1 for 6 h.The changes of cell morphology were observed by inverted microscope.The laser confocal microscopy was used to observe the microtubule changes.Western blot was applied to determine the expression of phosphorylation of tau protein,and apoptosis-regulating factors Bcl-2,Bax and Caspase-3.The changes of apoptotic cells were observed by TUNEL method.Results The normal SK-N-SH cells spread well.OA-treated cells showed that the cell axons and the microtubules were broken and decreased under the inverted microscope and laser confocal microscope.Preincubation of GS demonstrated the significantly protective effects against the morphologic damage induced by OA.In OA-treated group,the phosphorylation of tau protein at Ser-199/202 and Ser-404 sites was higher than that in normal group,and the non-phosphorylation of tau protein at the same sites was lower;Incubation of GS at the dose of 50 mg?L-1 and 100 mg?L-1 with the cells decreased the phosphorylation of tau protein Ser-199/202 and Ser-404 sites.GS group at the dose of 50 mg?L-1 and 100 mg?L-1 decreased the expression of at non-phosphorylation of tau protein at the Ser202 site.The apoptotic cells were not found in normal group.The number of apoptotic cells were obviously increased.the expression of Bax and caspase-3 significantly enhanced,and Bcl-2 expression decreased in the OA-treated model group.GS significantly decreased the apoptotic cell number of nerve cells,inhibited the expression of Bax and caspase-3.Conclusion GS can protect the nerve cells from pathological change induced by OA.Maybe because it can inhibit the hyperphosphorylation of tau protein and protect the nerve cells from apoptosis,thus GS may have potential to treat Alzheimer disease.

ObjectiveTo study the effect of SSY-B2 on improvement of learning/memory function of rats with bilateral fornix/fimbria transection.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. Half to 1 hour before operation, water or drugs were fed introgastrically to each group respectively. From the fourth week, Morris water maze and tunnel water maze tests were used. Escape latency of rats in Morris test, escape latency and errors in tunnel test were recorded.ResultsIn both Morris test and tunnel water maze test, low dosage and medium of SSY-B2 markedly shorten the escape latency or reduced the errors.ConclusionsSSY-B2 can ameliorate spatial learning/memory dysfunction produced by fornix/fimbria transection. Functional compensation in other neural structure other than regeneration of the septohippocampal pathway is considered to be responsible for the effects.

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.

ObjectiveTo observe the influence of mitochondrial cytochrome c oxidase(COX) decrease on cholinergic and dopaminergic system in brain of model rats.MethodsRats were administrated with 1mg/kg/h or 2mg/kg/h subcutaneously via an Alzet minipump for 30 days. Choline-acetyl-transfertase(ChAT) and acetylcholinesterase(AChE) activity in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. The contents of Norepinephrine(NE), dopamine, 5-hydroxytryptamine(5-HT) and their metabolic products in striatum were measured by HPLC.ResultsChAT activity was significantly inhibited in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. Therefore, the ratio of ChAT/AChE decreased in model rats. The content of NE, dopamine, 5-HT and their metabolic products in striatum were not different among all groups.ConclusionsCOX deficiency can induce abnormality of ChAT and AChE activity in model rats. Dysfunction of neurotransmitter-acetylcholine would be account for learning-memory deficiency. Model rats indicated cholinergic system deficit without any dopaminergic system abnormality, so chronic infusion of sodium azide via minipump may specially serve as a tool for developing the experimental model of Alzheimer's disease.