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 investigate effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), on learning and memory function and excitability in Alzheimer's disease rat model induced by cholinergic damage.MethodsBasal forebrain of rats were injured by ibotenic acid injection of 10μg each side. Rats were divided into six groups as the operation, model, positive control drug donepezil hydrochloride, TSG low (0.03g/kg), middle (0.06g/kg) and high (0.12g/kg) dose groups. These drugs were intragastrically administrated for 1 month. The learning and memory function were determined with Morris water maze, channel water maze and step through tests, and the excitability was evaluated by open field analysis. Results TSG (low, middle and high dose)significantly decreased the swimming time and error times (P<0.05) in water maze test and TSG high dose improved the ability of passive avoidance response at step through test.Open field test showed that there was no significant difference on excitability between each group ConclusionTSG can improve learning and memory abilities of Alzheimer's disease rat induced by cholinergic damage, TSG(low and middle dose)improve excitability of central nervous system in Alzheimer's disease rat model,but TSG dose maybe inhibite excitability of central nervous system.

ObjectiveTo explore the mechanism of protection of 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside(TSG) on brain.MethodsThe bilateral carotid arteries of mice were occluded and then reperfused. The mice were sacrificed to get the brain tissue. Brain water content(BWC) was assayed by dry-wet method; malondialdehyde (MDA) content was determined by thiobarbiturate method and the activity of superoxide dismutase(SOD) was estimated by nitrite salt assay.ResultsBWC of model group was significantly higher than that of sham-operation group, while the TSG treatment reduced the BWC remarkably in mice with ischemia-reperfusion. SOD activity of model group was significantly lower than that of sham-operation group, while MDA content increased remarkably. Comparing with the model group, the SOD activity of mice treated with TSG was higher and the MDA content was lower.ConclusionTSG may reduce brain edema, improve the anti-oxidative ability of the brain tissue, and therefore, have protective effects on the brain.

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.