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1.
Toki-Shakuyaku-San (TJ-23) is one of the most popular Kampo medicines in Japan and it is used for the treatment of ovarian dysfunction and menopausal syndrome in women. We have demonstrated that TJ-23 has a neuroendocrine effect and facilitates hypothalamic-controlled pituitary and ovarian functions. Furthermore, we have also observed that TJ-23 has a stimulatory effect for the synthesis and release of neurotransmitters, such as acetylcholine, dopamine and norepinephrine by activating related enzymes in the brain. Furthermore, TJ-23 increases the synthesis of nicotine acetylcholine receptors in the brain. Administration of TJ-23 facilitates memory related behaviour in experimental animals. In addition TJ-23 has a neuroprotective effect for neuron death. The clinical application of TJ-23 in open trials for patients with Alzheimer's disease improved their memory related behaviour and intellectual function. Moreover, treatment with TJ-23 provides motivation for daily life in Alzheimer-type patients with dementia. Basic research and clinical trials suggest strongly that TJ-23 has a therapeutic efficacy for the treatment of dementia of the Alzheimer type.  相似文献   

2.
We investigated the effects of Toki-shakuyaku-san (TSS, Tang-Kuei-Shao-Yao-San in Chinese), Japanese traditional herbal medicine, on the nervous and immune systems in ovariectomized mice as a climacteric disorder model. Female C57BL/6 mice were ovariectomized (OVX) and TSS was given daily through the drinking water for either 10 or 20 days from the day after ovariectomy. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for choline acetyltransferase (ChAT) activity and norepinephrine contents. The mitogenic activities, alkaline phosphatase activity and 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H terazolium bromide (MTT) activity, in splenic lymphocytes has also measured. Furthermore, the effects of TSS on learning and memory ability were studied by the step-through type passive avoidance test. As the results, the administration of TSS significantly suppressed the decrease of ChAT activity in the cerebral cortex (CC) and the dorsal hippocampus (DH) of ovariectomized mice at 10 days after ovariectomy, however no significant effect was observed at 20 days after ovariectomy. Norepinephrine contents in OVX group were decreased at 10 and 20 days after ovariectomy in the CC and the ventral hippocampus (VH). The administration of TSS significantly suppressed the decrease of norepinephrine contents at 20 days after ovariectomy. The mitogenic activities of lymphocyte in spleen were increased at 10 days after ovariectomy, and decreased at 20 days after ovariectomy. However, the suppression of these changes was observed in the group given TSS. The mean latent period was also shortened in the passive avoidance test in the OVX group, but TSS treated group improved mean latency. From these observations, it is inferred that administration of TSS brings on the synthesis of acetylcholine and norepinephrine in the CC and hippocampus, and may improve the memory related behavior and the abnormalities in lymphocytes in the models of the climacteric disorder.  相似文献   

3.
目的:观察针刺对神经干细胞(NSCs)海马内移植老年性痴呆(AD)大鼠学习记忆和脑内胆碱能系统的影响,探讨针刺治疗老年性痴呆的机制.方法:采用β -淀粉样蛋白(β- AP)向海马CA1区定向注射制做AD模型,将大鼠分为5组:正常组、模型组、移植组、针刺组和移植针刺组,每组各12只.针刺选取百会、大椎、人中3个穴位,并接通电针仪.大鼠跳台检测行为学指标;酶免法检测大脑皮层及海马组织胆碱乙酰转移酶(CHAT)含量.结果:移植针刺组大鼠跳台学习、记忆所需次数比模型组减少(P<0.05);移植针刺组大脑皮层及海马组织ChAT含量比模型组提高(P<0.05),与移植组比较有显著性差异(P<0.05).结论:针刺对大鼠脑内胆碱能系统的改善是治疗AD的作用机制之一,针刺结合神经干细胞移植治疗效果更佳.  相似文献   

4.
 目的 探讨雌二醇和人参总皂苷对去卵巢大鼠记忆障碍的改善作用及可能的机制。方法 利用成年去卵巢大鼠,通过Morris水迷宫方法观察去卵巢大鼠学习记忆功能的改变以及雌二醇和人参总皂苷对其改善作用,测定去卵巢大鼠胆碱乙酰转移酶(ChAT)的活性并观察药物对此酶活性变化的影响。结果 雌二醇和人参总皂苷可以有效地阻止因去卵巢而造成的大鼠空间学习记忆能力的降低,并能逆转因去卵巢所引起的前脑皮层和海马中ChAT酶活性的降低。结论 雌二醇和人参总皂苷有改善因去卵巢所致大鼠记忆功能障碍的作用,其机制可能与它们能促进脑内乙酰胆碱的合成有关。  相似文献   

5.
The aim of this study was to investigate the effect of a BuOH-soluble fraction from Dracocephalum tanguticum Maxim (DME), which contained 52% of total flavonoid, on the cerebral ischemia injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. RT-PCR and Western blot analysis showed that DME (30 mg/kg/day for seven days) by intragastric administration modulated the mRNA expression and protein synthesis of two neurotrophic factors: brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). DME was effective in stimulating BDNF mRNA expression and protein synthesis in the ipsilateral frontal cortex (IFC) of both the sham-operated and pMCAO rats and this effect was also observed in the hippocampus of the pMCAO rats. DME significantly increased NT-3 mRNA expression and protein synthesis in the IFC and hippocampus of the pMCAO rats, although it had no effect on NT-3 expression in the sham-operated groups. Meanwhile, DME also decreased the malondialdehyde contents in the hippocampus of the sham-operated and pMCAO groups, and significantly attenuated the decrease of endogenous antioxidant (superoxide dismutase, glutathione peroxidase and catalase) activities in both the IFC and hippocampus of the rats after ischemia insult injury. Moreover, DME facilitated the neurobehavioral recovery after the cerebral ischemia. These findings suggested that DME has potential for treatment of ischemia-induced brain damage through stimulation of antioxidant activity and neurotrophic factor synthesis.  相似文献   

6.
目的 :探讨电针对慢性应激致空间学习记忆障碍大鼠海马胆碱能功能的影响。方法 :采用电击足底结合噪声应激建立大鼠学习记忆障碍模型 ,Morris水迷宫观察动物的空间学习记忆能力 ,放免法检测乙酰胆碱 (Ach)含量、胆碱乙酰转移酶 (ChAT)和乙酰胆碱酯酶 (AchE)活性。结果 :慢性应激可引起大鼠空间学习记忆功能障碍 ,海马Ach含量减少 ,ChAT和AchE活性降低。电针对上述改变有显著的保护作用。结论 :电针改善慢性应激引起的大鼠空间学习记忆功能障碍可能与其增强海马胆碱能系统的功能有关。  相似文献   

7.
该研究的目的是利用线粒体细胞色素C氧化酶抑制剂叠氮钠致痴呆动物模型,观察参乌胶囊对模型大鼠学习记忆障碍的改善作用及其机制.应用SD大鼠皮下埋植Alzet微泵,连续恒速给予叠氮钠(1 mg· kg-1·h-1)共30 d造模.手术后24 h开始给药,参乌胶囊低、中、高剂量组(干粉0.45,0.9,1.8g· kg-1)每日灌胃给药1次.应用水迷宫、避暗试验检测动物学习记忆能力.放射免疫法测定大脑皮层和海马胆碱乙酰基转移酶(ChAT)活性,羟胺比色法检测乙酰胆碱酯酶(AChE)活性,放射配基结合试验测定M-胆碱能受体结合力.结果显示,微泵恒速灌注叠氮钠导致模型大鼠水迷宫游出时间及距离延长,避暗潜伏期缩短、错误次数增加.模型大鼠大脑皮层和海马ChAT活性降低,海马区AChE活性升高,皮层和海马M-胆碱能受体结合力明显下降.参乌胶囊灌胃给药能够明显减少模型大鼠水迷宫游出时间及距离,延长避暗潜伏期、减少错误次数;并且降低模型大鼠脑内AChE活性,升高ChAT活性及M-胆碱能受体结合力.实验结果表明,参乌胶囊明显改善线粒体缺陷致痴呆模型大鼠学习记忆能力,其药理作用机制与改善脑内胆碱能系统功能相关.提示参乌胶囊可干预线粒体缺陷这一AD早期的病理改变,进而拮抗其后出现的AD特征性病理变化,对于AD的治疗具有重要的应用价值.  相似文献   

8.
目的探讨去卵巢大鼠端脑皮质和海马病理改变及氨基胍和补肾方药的防治效应,为阿尔茨海默病防治药物筛选提供参考。方法将36只雌性SD大鼠随机分为假切除组、去卵巢组、氨基胍防治组和补肾方药防治组,各9只。去卵巢组、氨基胍防治组和补肾方药防治组行背部切口切除双侧卵巢,假切除组切除腹腔等体积的脂肪组织。切除卵巢4周后氨基胍防治组饮用1‰盐酸氨基胍水溶液,剂量为盐酸氨基胍50mg/(kg·d);补肾方药防治组予补肾方药灌胃,剂量为生药6.3g/(kg·d);去卵巢组和假切除组予与补肾方药防治组相应容积自来水灌胃。喂养16周后,取脑组织观察端脑皮质和海马的病理改变。结果去卵巢组大鼠端脑皮质及海马组织出现神经元颗粒变性和神经原纤维缠结等,氨基胍防治组和补肾方药防治组神经元的变性现象及神经原纤维缠结明显改善,且在受损区周围有致密的神经纤维网出现。结论去卵巢大鼠可出现阿尔茨海默病样脑病理改变,氨基胍和补肾方药均可防治上述病理改变且促进脑受损区周围致密神经纤维网形成。  相似文献   

9.
 目的研究何首乌有效成分二苯乙烯苷(2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷,简称TSG)对胆碱能损伤致痴呆大鼠的保护作用。方法采用鹅膏覃氨酸(IBO)基底前脑注射造成模型大鼠脑内胆碱能系统损伤,模拟老年性痴呆动物模型。实验分为假手术、模型、阳性对照药盐酸多奈哌齐(多奈哌齐1.2mg·kg-1)、TSG小剂量(30mg·kg-1)、中剂量(60mg·kg-1)和大剂量(120mg·kg-1)组,灌胃给药1个月后,取脑分区测定皮层和海马胆碱乙酰基转移酶、乙酰胆碱酯酶活性,M-胆碱能受体结合力。胆碱乙酰基转移酶活性测定用放射化学法,乙酰胆碱酯酶活性测定用羟胺比色法,M-胆碱能受体结合力测定用放射配基结合实验。结果IBO模型大鼠皮层和海马胆碱乙酰基转移酶活性降低,M-胆碱能受体结合力明显下降;皮层乙酰胆碱酯酶活性下降。TSG小剂量可提高模型大鼠皮层和海马胆碱乙酰基转移酶活性;对于M-胆碱能受体结合力的下降,TSG各剂量组均有明显的改善作用;对于皮层乙酰胆碱酯酶活性的下降,TSG中、大剂量组有一定提升作用。结论TSG可明显改善模型动物胆碱能系统的损伤,对于老年性痴呆的治疗有重要意义。  相似文献   

10.
27-day-old female rats received 20 IU PMS and 56 hours later, 40 IU hCG and were orally given with 20 or 200 micrograms of Hachimijiogan (TJ-7), Tokishakuyakusan (TJ-23) or Keishibukuryogan (TJ-25) daily for 3 or 5 days before sacrifice. Seven days after hCG treatment, the serum and ovarian tissue were assayed for progestins. 200 micrograms/day of TJ-23 significantly (p less than 0.05) decreased the progesterone and 17 alpha-hydroxyprogesterone levels, whereas it significantly (p less than 0.01) increased 20 alpha-hydroxyprogesterone. TJ-7 and TJ-25 showed a tendency to decrease these progestins. These results suggest that TJ-23 has a luteolytic effect on the corpus luteum in vivo.  相似文献   

11.
目的 :运用自由基学说和胆碱能学说 ,探讨针刺对拟阿耳茨海默氏病 (AD)大鼠大脑皮质及海马抗氧化能力和胆碱能系统功能的影响。方法 :应用迷宫试验观测针刺对拟AD大鼠学习记忆能力的影响 ;并应用分光光度法测定大鼠大脑皮质中丙二醛 (MDA)含量及谷胱甘肽过氧化物酶 (GSH Px)、超氧化物歧化酶 (SOD)活性变化 ,应用巯基比色分析法、免疫组化方法测定大鼠海马区乙酰胆碱酯酶 (AChE)和胆碱乙酰化酶 (ChAT)活性变化。结果 :迷宫学习记忆能力测试表明 ,针刺组大鼠成绩好于模型组 (P <0 .0 1) ;针刺组大鼠大脑皮质中MDA含量比模型组显著降低(P <0 .0 1) ,而SOD和GSH Px活性明显升高 (P <0 .0 1) ;在AChE和ChAT测定中 ,针刺组比模型组大鼠AChE、ChAT活性明显增强 (P <0 .0 1)。结论 :针刺可增强脑内抗氧化能力 ,减轻脑内自由基对神经元的损伤 ,从而改善AD的病理反应 ,提高中枢胆碱能系统功能 ,缓解拟AD大鼠的学习记忆障碍  相似文献   

12.
目的:探讨地黄饮子对慢性脑低灌注大鼠学习记忆及海马乙酰胆碱酯酶(AChE)、乙酰胆碱转移酶(ChAT)的影响。方法:采用双侧颈总动脉结扎制作大鼠慢性脑缺血模型,通过Morris水迷宫试验测定地黄饮子对慢性脑低灌注大鼠学习记忆功能改善情况,并测定大鼠海马脑组织AChE,ChAT的含量。结果:地黄饮子组(10,20 g.kg-1)与模型对照组比较,Morris水迷宫试验逃避潜伏期缩短,跨越平台次数增加,海马AChE和ChAT含量显著升高(P<0.05)。结论:地黄饮子能改善慢性脑低灌注大鼠学习记忆功能,可能与保护胆碱能系统有关。  相似文献   

13.
In the cobalt focus experimental epilepsy model, severe hippocampal neuron damage occurs with marked EEG changes. The effects of TJ-960, a herbal medicine formulation, were studied on neuron damage in the CA1 area of rat hippocampus. Continuous oral administration of TJ-960 from one month prior to the cobalt application showed almost complete protection against hippocampal neuron damage induced by cobalt application to the cerebral cortex. TJ-960 also completely inhibited the EEG changes as well as the brain edema induced by cobalt application.  相似文献   

14.
The active principles of Withania somnifera (WS, 20–50 mg/kg, p.o.), consisting of equimolar amounts of sitoindosides. VII–X and withaferin A, were investigated for putative nootropic activity in an experimentally validated Alzheimer's disease (AD) model. The syndrome was induced by ibotenic acid (IA) lesioning of the nucleus basalis magnocellularis (NBM) in rats. Cognitive deficits induced in NMB-lesioned rats were assessed by attenuation of a learned active avoidance task and a decrease in frontal cortical and hippocampal acetylcholine (ACh) concentrations, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptor (MCR) binding. IA-induced NBM lesioning in rats caused a marked cognitive deficit, as evidenced by severe reduction of the learned task, and was accompanied by a significant decrease in frontal cortex and hippocampal ACh levels, ChAT activity and MCR binding. WS (50 mg/kg) significantly reversed both IA-induced cognitive deficit and the reduction in cholinergic markers after 2 weeks of treatment. The findings validate the medharasayan (promoter of learning and memory) effect of W. somnifera, as has been reported in Ayurveda.  相似文献   

15.

Aim of this study

Aim of the present study is to clarify the effects of yokukansan (TJ-54) on learning and non-cognitive disturbances in the Tg2576 mouse expressing the human form of the APP695SWE (APP-Tg mice), which is considered to be an animal model of Alzheimer's disease.

Materials and methods

Powdered diets containing 0.5 and 1.0% TJ-54 were given to the mice for 10 months (from 5 to 15 months old). The Morris water-maze test, elevated plus-maze test, and open-field test were performed for evaluation of learning and non-cognitive disturbances.

Results

Treatment with 1.0% TJ-54 for 5 months shortened the time it took for APP-Tg positive (+) mice to reach the platform in the Morris water-maze test. In the elevated plus-maze test, treatment with 1.0% TJ-54 for 2 months significantly reduced the increased number of entries and the time spent in open arms observed in APP-Tg(+) mice. In an open-field test, treatment of 1.0% TJ-54 for 9 months significantly suppressed the increase in locomotion observed in APP-Tg(+) mice.

Conclusion

These results suggest the possibility that TJ-54 ameliorates learning deficits and non-cognitive defects including a decrease in the anxiety (or disinhibition) and an increase in locomotor activity (hyperactivity) observed in APP-Tg(+) mice.  相似文献   

16.
Levels of monoamines and metabolites, excitatory amino acids, and gamma-aminobutyric acid (GABA) were investigated in discrete brain areas of chronic Jiawey Siwu (JS)-treated rats. Male Sprague-Dawley rats were dosed orally for 3 months with normal saline or JS at 0.21, 1.05 or 4.2 g/kg/day. Body weights of these four groups were similar over 3 months. Most effects of JS revealed a dose dependency with levels of neurotransmitters. Levels of norepinephrine (NE) and epinephrine (EPI) in cerebral cortex; EPI, vanillylmandelic acid (VMA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in medulla oblongata; DA in midbrain; NE and 5-HT in amygdala; and 5-HT in hypothalamus had decreased in JS-treated rats. 3-Methoxytyramine (3-MT) in cerebral cortex; 5-hydroxyindole-3-acetic acid (5-HIAA) in medulla oblongata; NE, 3-MT and homovanillic acid (HVA) in pons; EPI and 3-MT in midbrain; 3-MT and HVA in amygdala; 3-MT, 3,4-dihydroxyphenylacetic acid (DOPAC), HVA and 5-HIAA in cerebellum; HVA in hypothalamus; and DOPAC and HVA in hippocampus had all increased in JS-treated rats. In pons, 5-HT increased with low and decreased with high JS doses. Ratios of DA/3-MT in pons and midbrain; DA/HVA in pons and cerebellum; and 5-HT/5-HIAA in medulla oblongata, cerebellum and hypothalamus had decreased. Furthermore, aspartate (ASP) and glutamate (GLU) levels had decreased in cerebral cortex, midbrain, hypothalamus and hippocampus or amygdala, and increased in pons. GABA levels were reduced in cerebral cortex, and higher in medulla oblongata, pons, amygdala, cerebellum, hippocampus and striatum of JS-treated rats. These results indicate that the synthesis and (or) metabolism of NE, DA, EPI and 5-HT, and the levels of ASP, GLU and GABA in rat brains were differentially regionally altered by JS, which may contribute to the central manifestations of JS treatment.  相似文献   

17.
目的:观察丁基苯酞(dlNBP),dNBP和lNBP对脑缺血后皮层和纹状体中以及低糖低氧和NMDA刺激后培养的胎鼠皮层神经元中胆碱乙酰化酶活性变化的影响。方法:大脑中动脉堵塞起始处造成大鼠局灶性脑缺血;胎鼠皮层神经元以低糖低氧培养基培养造成低糖低氧模型;胆碱乙酰化酶活性以分光度法进行测定。结果:脑缺血后缺血区皮层和纹状体中胆碱乙酰化酶活性分别下降了61.3%和58.4%。dlNBP,dNBP和lNBP(10和20mg·kg-1,ip)于脑缺血后5和60min给药2次皆可显著提高脑组织中胆碱乙酰化酶活性。dlNBP,dNBP和lNBP(0.1~10μmol·L-1)对低糖低氧及NMDA刺激后神经细胞中胆碱乙酰化酶活性也有明显的提高作用。结论:dlNMP改善局灶性脑缺血后动物的学习记忆功能可能与其对胆碱能神经功能的改善有关。  相似文献   

18.
刘羽  刘林  易亚乔  刘丽  肖波  刘检  邵乐 《中华中医药学刊》2020,(3):95-99,I0018,I0019,I0020,I0021
目的研究百事乐加味方(MBD)对脑卒中后抑郁症(Post-stroke depression,PSD)大鼠炎症因子IL-1β、IL-6、TNF-α含量及海马(HP)、前额叶皮层(PFC)组织NF-κB表达水平的影响,从炎症平衡角度探讨复方中药防治该病可能机制。方法采用MCAO+CUMS+孤养法复合因素建立PSD模型,记录大鼠每周体重;采用ELISA方法,检测PSD大鼠血清炎症因子IL-1β、IL-6和TNF-α的含量;采用免疫组化技术检测HP、PFC组织NF-κB的表达水平。结果对体质量影响,与PSD大鼠比较,MBD组在应激第14、21、28天能够恢复模型大鼠体重,差异具有统计学意义(P<0.01~0.05);对炎症相关指标影响,与PSD大鼠比较,MBD高剂量组明显降低大鼠血清中IL-1β,IL-6、TNF-α含量,明显降低大鼠HP、PFC组织NF-κB水平,差异有统计学意义(P<0.01~0.05);MBD低剂量组明显降低大鼠血清中IL-6,TNF-α含量及大鼠HP、PFC组织NF-κB表达水平,差异有统计学意义(P<0.05)。与卒中组比较,MBD高剂量组明显降低大鼠血清中IL-1β、IL-6含量,同时降低HP、PFC组织NF-κB的表达水平,差异有统计学意义(P<0.05);低剂量治疗组HP、PFC组织NF-κB水平明显降低,差异有统计学意义(P<0.01~0.05)。与抑郁组比较,MBD高剂量组明显降低大鼠血清中IL-1β含量,HP、PFC组织NF-κB的表达水平明显降低,差异有统计学意义(P<0.01~0.05);MBD低剂量组HP、PFC组织的NF-κB表达水平略降低,但差异不具有统计学意义(P>0.05)。结论 MBD能有效抑制PSD大鼠相关炎症反应因子,同时降低HP、PFC组织NF-κB表达水平,改善PSD大鼠脑神经功能,从而发挥治疗作用,是其抗脑卒中后抑郁重要机制之一。  相似文献   

19.
The ethanolic extract from the leaves of Ocimum sanctum Linn was screened for its effects on the noise induced changes in the central cholinergic system of albino rats by investigating the acetylcholine content and acetylcholinesterase activity in discrete areas of brain. Exposure to noise (10 kHz:100 dB) stress for 30 min caused a significant reduction in total acetylcholine content and increase in the activity of acetylcholinesterase in cerebral cortex, corpus striatum, hypothalamus and hippocampus of brain. Pretreatment of the animals with ethanol extract of Ocimum sanctum leaves for 7 days prevented the noise induced changes in these two cholinergic parameters in all the four areas of brain. The results of the study indicate the protective nature of the plant material on the brain tissues against the detrimental effect of noise stress.  相似文献   

20.
目的:观察中药复方脑益康对阿尔茨海默病(Alzheimer’s disease,AD)大鼠脑组织胆碱乙酰基转移酶(choline acetyltransferase,ChAT)表达的影响。方法:采用大鼠双侧Meynert核(nucleus basalis of Meynert,NBM)注射鹅膏蕈氨酸(ibotenic acid,IBO)建立AD动物模型,灌胃给药28 d后,应用免疫组织化学染色和Western-blot印迹分析观察ChAT在AD大鼠额叶皮层的表达。结果:脑益康改善脑组织ChAT阳性神经元的形态及数量、增加ChAT蛋白的表达。结论:脑益康通过促进ChAT蛋白合成,增加乙酰胆碱(acetylcholine,ACh)的合成,从而保护中枢胆碱能神经元。  相似文献   

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