RESUMO
BACKGROUND: Tiantai I consists of gastrodia, Chinese angelica root, areca seed. It has been considered as the roles of invigorating the liver, nourishing marrow, heightening the intelligence and causing resuscitation. OBJECTIVE: To observe the effects of Tiantai Ⅰ on the abilities of learn ing and memory and the activity of central cholinergic system in mice withspontaneous Alzheimer disease. DESIGN: A randomized control observation. SETTING: Shenzhen Institute of Integrated Chinese and Western Medicine. MATERIALS: Male Kunming mice of 13 months old were raised to 21 months old, of which 52 with spontaneous Alzheimer disease werescreened. They were randomly divided into blank control group, westerndrug control group, Tiantai Ⅰ 6.80 and 20.41 g/kg groups, 13 mice in eachgroup. Another 13 aged mice with normal learning and memory abilitieswere selected as the normal control group at the same time. METHODS: Mice in the western drug control group were treated with0.6 mg/Kg Hydergine, those in the Tiantai Ⅰ 6.80 and 20.41 g/kg groupswere given intragastric administration of Tiantai Ⅰ of 6.80 and 20.41 g/kg, respectively, and those in the normal control group and blank control groupwere given double distilled water of the same volume. The learning andmemory results were examined by the step-down test. Freezing sections ofbrain tissue were prepared, acetylcholinesterase (AChE) fiber was showedaccording to the Hedreen method, and choline acetyltransferase (ChAT) was detected with Burt and Silver methods, the automatic image analysissystem for biomedical application was applied in the quantitative analysisof AChE fiber and ChAT activity. MAIN OUTCOME MEASURES: ① Effect of Tiantai Ⅰ on the abilities of learning and memory in mice with Alzheimer disease; ② AChE fiberarea density in temporal cortex and hippocampal CA1 region; ③ ChAT ac tivity in Meynert nuclei of basal forebrain. RESULTS: ① Tiantai Ⅰ in ameliorating the abilities of learning and mem ory in mice with spontaneous Alzheimer disease: The error times in theTiantai Ⅰ 6.80 and 20.41 g/kg groups, normal control group and westerndrug control group were obviously fewer than that in the blank controlgroup (5.08±2.18, 3.77±1.48, 3.25±1.27, 6.17±3.12, 9.31±3.65, P ＜ 0.05). ② AChE fiber area density: The AChE fiber area densities in temporalcortex were obviously higher in the Tiantai Ⅰ 6.80 and 20.41 g/kg groups, normal control group and western drug control group than in the blankcontrol group (20.19±4.18, 25.01±6.44, 26.38±6.52, 19.44±4.33, 14.36±3.21, P ＜ 0.05). The AChE fiber area densities in hippocampal CA1 region were obviously higher in the Tiantai Ⅰ 20.41 g/kg groups and nor mal control group than in the blank control group, western drug controlgroup and Tiantai Ⅰ 6.80 g/kg group (13.88±3.07, 14.11±4.36, 6.57±2.30, 10.13±2.94, 9.63±2.40, P ＜ 0.05). ③ ChAT activity: It was obviously high er in the TiantaiI 20.41 and 6.80 g/kg groups, western drug control groupand normal control group than in the blank control group (0.683±0.179, 0.589±0.179, 0.552±0.173, 0.705±0.141, 0.354±0.131, P ＜ 0.05). CONCLUSION: Tiantai Ⅰ can significantly improve the disturbances oflearning and memory in mice with spontaneous Alzheimer disease, and itcan increase the activity of central cholinergic system in a dose-dependentmanner.
RESUMO
BACKGROUND: The theory of free radical on onset of Alzheimer disease(AD) and the relationship between oxidative damage and onset of AD have made anti-oxidative drugs become the hot topic in researches. Whether does the action of natural Chinese herbs on anti-injury of oxygenic free radical produce intervention on AD?OBJECTIVE: To observe the effects of developed and researched tiantai I,the natural Chinese herb, on learning and memory function and metabolism of oxygenic free radical in the model of spontaneous AD.DESIGN: Completely randomized experimental study based on the experimental animals.SETTING: Clinical Institute of Chinese-Western integration of City-grade.MATERIALS: The experiment was performed in 2nd grade Animal Experimental Room of Clinical Institute of Chinese-Western integration in Shenzhen. Kunming male mice of clean grade were employed, at the age of 13 months, mass weighted varied from 40 to 50 g and from Experimental Animal Center of Zhongshan Medical University(Qualified No. 95A07).INTERVENTIONS: When the experimental animals were bred till 21 months, AD mice were screened from the aged animals according to International Universal Standards and Methods. The experimental animals were randomized into blank control, western-drug control, the small dosage of tiantai I group(small dosage group), the large dosage of tiantai I group(large dosage group) and learning and senile normal-memory group(senile normal group) in addition. In western-drug control, hydergine 0.6 mg/kg was administrated, and in small and large groups, tiantai I of 6. 80 g/kg and 20.41 g/kg were administrated respectively, continuously for 60 days. The double-distilled water of equal dosage was infused in both blank control and senile normal group.MAIN OUTCOME MEASURES: Step-down test was applied to determine learning and memory scores. Froze sections of brain tissue were prepared and immuno-histological-chemical method was used to display the superoxidative dismutase(SOD) activity in cerebral cortex and hippocampus. Ultrathin section of brain tissue in hippocampal CA1 was prepared and transmission electron microscope(TEM) was used to observe cellular lipofuscin in neuron. Automatic image analysis system for biomedical application was used to determine in quantity SOD and lipofuscin.RESULTS: Learning and memory of AD mice were significantly decreased ( P ＜ 0.01 ) . Tiantai I improved significantly learning and memory disturbance of mice in the model of spontaneous AD( P ＜ 0.05- 0.01),markedly enhanced SOD activity in central cerebral cortex and hippocampus ( P ＜ 0.05 - 0.01 ) and reduced cellular lipofuscin content of neuron( P＜ 0.05 -0.01 ). In addition, it provided certain of quantitative reaction.CONCLUSION: For the mice with spontaneous senile dementia, learning and memory as well as SOD activity of neuron in relevant cerebral areas are decreased remarkably and lipofuscin is increased significantly. Tiantai I acts significantly in pharmacodynamics on anti-injury of oxygenic free radical,increases significantly SOD activity, decreases lipofuscin content and improves the ultrastructure of neuron in cortex and hippocampus in AD mice.
RESUMO
BACKGROUND: The synaptic plasticity of central nerves is the key basis of behavior-dependent learning and memory, there have been few reports about weather the Chinese herbal medicine for treatment of Alzheimer disease is through enhancing synaptic plasticity to improve learning and memory.OBJECTIVE: To investigate the effect of tiantai No. 1 recipe on learning and memory function and synaptic plasticity of spontaneous Alzheimer disease models.DESIGN: A randomized and controlled trial.SETTING: Institute of Combination of Traditional Chinese Medicine and Western Medicine of Shenzhen.MATERIALS: The experiment was completed at the grade Ⅱ Laboratory of Institute of Combination of Traditional Chinese Medicine and Western Medicine of Shenzhen City. The experimental animals were mice of Kunming strain.METHODS: Totally 52 Kunming mice, aged 21 months, with spontaneous Alzheimer disease (memory impairment) were chosen, and at random divided into 4 groups: senile dementia, western drug control, tiantai No. 1recipe 6.80 g/kg and 20.41 g/kg groups; besides 13 mice with normal learning and memory power were chosen as normal senile group. Hydergine 0.6 mg/kg was given for mice in western drug control group, tiantai No. 1recipe 6.80 g/kg and 20.41 g/kg were respectively given for mice in tiantai No. 1 recipe 6.80 g/kg and 20.41 g/kg groups. The medicines above were all prepared into 0.5 mL solution and given by gavage, for consecutive 60 days. The mice in normal senile and senile dementia groups were given double distilled water of the same volume. The learning memory power was tested by jumping stand; ultrathin cerebral section of hippocampal CA1 region was examined with transmission electron microscope,and some parameters of synaptic plasticity was also quantitatively detected with automatic micrographic analysis system.MAIN OUTCOME MEASURES: ① The effect of tiantai No. 1 recipe in different doses on learning and memory of spontaneous Alzheimer disease mice. ② Observation of synapse with electron microscope and quantitative examination stereologically.RESULTS: All animals involved in the trial entered the final result analysis without any loss. ① The effect of tiantai No. 1 recipe in different doses on learning and memory of spontaneous Alzheimer disease mice: The error numbers of learning and memory in tiantai No. 1 recipe 6.80 g/kg and 20.41 g/kg groups were smaller than that in senile dementia group,and the error number of learning in tiantai No. 1 recipe 6.80 g/kg group was smaller than that in tiantai No. 1 recipe 20.41 g/kg group. The escape latent periods of learning training was smaller than that in senile dementia group and the safe platform latent periods of memory in tiantai No. 1 recipe 6.80 g/kg and 20.41 g/kg groups were longer than that in senile dementia group, and the safe platform latent period of memory in tiantai No. 1 recipe 6.80 g/kg group was smaller than that in 20.41 g/kg group. ② Observation of synapse with electron microscope and quantitative examination stereologically: Compared with the mice in normal senile group, for mice in senile dementia group, there occurred degenerative phenomena: the number of synapses reduced, a part of synaptic clefts were not clear, the synaptic junction was interrupted, and he sizes of synaptic vesicles were different; in the rest groups there were also degenerative phenomena, however the degrees were milder than those in the model group. Tiantai No. 1 recipe could remarkably raise the number density and sectional density of synapses in the hippocampal CA1 region, and the increased extents in 20.41 g/kg tiantai No.1 recipe was larger than those in 6.80 g/kg tiantai No. 1 recipe.CONCLUSION: Tiantai No. 1 recipe can remarkably improve their learning and memory impairments, which may be related with that it promotes re-generation of synapse and improves the plasticity of cerebral synapses;and the action presented a relationship of dose-effect.