石杉碱类似物异香兰石杉碱甲对胆碱酯酶的抑制作用和东莨菪碱导…

研究石杉碱类似物异香兰石杉碱甲（ＩＶＨＡ）对胆碱酯酶的抑制作用和东莨菪碱导致的记忆障碍的影响。方法：乙酰胆碱脂酶和丁酰胆碱酶活力用Ｅｌｌｍａｎ比公法测定。抑九Ｋｉ值和抑制机制用Ｌｉｎｅｗｅａｖｅｒ和Ｂｕｒｋ的双倒数作图测定。行为测试用八臂迷宫装置。结果：ＩＶＨＡ的抗ＡＣｈＥ作用弱于Ｈｕｐ－Ａ。它对红细胞膜ＡＣｈＥ作用稍０．１１μｍｏｌＬ－１。作用强于Ｐｈｙｓ和Ｇａｌ。属混合型制剂，Ｋｉ值为３２ｎｍ     

石杉碱甲透皮控释贴片对小鼠学习记忆的改善作用

目的:观察石杉碱甲透皮控释贴片(Hup -ATDDS)对正常小鼠及记忆障碍模型小鼠学习记忆功能的影响。方法:跳台试验测定Hup -ATDDS对正常小鼠学习成绩的影响;建立东莨菪碱记忆获得障碍模型及亚硝酸钠记忆巩固障碍模型,采用一次性训练的空间辨别反应实验-电迷宫实验和一次性学习的回避性条件反射试验-跳台试验测定小鼠记忆功能,观察Hup-ATDDS对其影响。结果:Hup -ATDDS 5 3.4 μg/只对正常小鼠跳台试验有促进学习成绩作用,对1mg/kg东莨菪碱引起的记忆获得障碍及12 0mg/kg亚硝酸钠产生记忆巩固障碍有明显的反转作用。结论:石杉碱甲透皮控释贴片具有较好的促进正常小鼠及记忆障碍小鼠的学习记忆功能作用     

石杉碱甲改善老年大鼠水迷宫操作记忆障碍(英文)

目的:测试石杉碱甲对自然衰老及东莨菪碱导致的空间记忆缺损的作用。方法:采用大鼠的水迷宫操作,检测石杉碱甲对获得及记忆的作用。结果:连续7天获得试验期间,皮下注射石杉碱甲0.1-0.2mg/kg能明显缩短老年大鼠找到平台的潜伏期。在第8天撤去平台的记忆测试,石杉碱甲0.1,0.2与0.4 mg/kg明显延长老年大鼠在该平台区的游泳时间。单次腹腔注射东莨菪碱0.1mg/kg明显损害已训练达标老年大鼠的空间记忆。皮下注射石杉碱甲0.4 mg/kg明显翻转东莨菪碱产生的记忆损害作用。结论:石杉碱甲能改善老年大鼠自然衰老或东莨菪碱产生的记忆障碍。     

石杉碱甲透皮控释贴片对小鼠学习记忆的改善作用

目的：观察石杉碱甲透皮控释贴片（Hup-ATDDS)对正常小鼠及记忆障碍模型小鼠学习记忆功能的影响。方法：跳台试验测定Hup-ATDDS对正常小鼠学习成绩的影响；建立东莨菪碱记忆获得障碍模型及亚硝酸钠记忆巩固障碍模型。采用一次性训练的空间辨别反应实验-电迷宫实验和一次性学习的回避性条件反射试验-跳台试验测定小鼠记忆功能，观察Hup-ATDDS对其影响。结果：Hup-ATDDS53.4μg/只对正常小鼠跳台试验有促进学习成绩作用。对1mg/kg东莨菪碱引起的记忆获得障碍及120mg/kg亚硝酸钠产生记忆巩固障碍有明显的反转作用。结论：石杉碱甲透皮控释贴片具有较好的促进正常小鼠及记忆障碍小鼠的学习记忆功能作用。     

石杉碱类似物在体外对胆碱酯酶的抑制作用(英文)

用比色法测试表明,14个半合成类似物的抗AChE作用均弱于Hup-A,左旋二氢及四氢类似物的抗BuChE作用稍强于Hup-A,前者属混合型抑制剂,K_i值为0.12μmol·L~(-1)。后者属竞争型抑制剂,K_i值为0.56μmol·L~(-1)。二者不同于异氟磷,与AChE为可逆性结合。     

石杉碱甲对基底核大细胞部损毁所致工作记忆障碍的影响

目的：研究石杉碱甲对基底核大细胞部（ＮＢＭ）损毁诱导的工作记忆障碍的影响。方法：采用八臂迷宫延迟板程序研究空间记忆。胆碱乙酰转移酶（ＣｈＡＴ）活力测定采用［＾３Ｈ］乙酰辅酶Ａ转变成［＾３Ｈ］乙酰胆碱的方法。结果：单侧损毁ＮＢＭ（卡因酸０．０２μｍｏｌ）导致空间记忆障碍。在不同的延迟间隔，大鼠完成程序产生的正确数减少和错误数增多。损毁侧大脑皮层ＣｈＡＴ酶的含量下降了大约４０％。石杉碱甲（０．２ｍｇ·     

石杉碱甲治疗缓解期精神分裂症记忆障碍的临床观察

目的:观察石杉碱甲治疗缓解期精神分裂症记忆障碍的疗效及不良反应。方法:将符合条件的60例缓解期精神分裂症患者随机分为两组,每组30例,分别用石杉碱甲200～400μg/d和安慰剂治疗,疗程12 wk,治疗前后进行临床记忆量表及不良反应量表评定。结果:石杉碱甲对恢复期分裂症记忆障碍的疗效显著优于安慰剂(P<0.05),而不良反应与安慰剂无显著性差异(P>0.05)。结论:石杉碱甲能有效改善缓解期精神分裂症的记忆功能,且不良反应轻微,毒性小。     

石杉碱甲对D-半乳糖诱致衰老小鼠脑抗氧化能力和胞浆钙离子的影响

目的:探讨石杉碱甲对D-半乳糖诱致衰老小鼠脑抗氧化能力和胞浆钙离子的影响。方法:连续皮下注射D-半乳糖(1000mg.kg-1.d-1)8周制备小鼠衰老模型,并于第3周开始灌胃给予石杉碱甲(0.8,0.4,0.2mg.kg-1)和维生素E(100mg.kg-1)处理;8周后采用水迷宫测定小鼠学习记忆能力,并取脑组织测定谷胱甘肽过氧化物酶(GSH-Px)和琥珀酸脱氢酶(SDH)活性,测定一氧化氮(NO)含量和一氧化氮合酶(NOS)活性及Fura-2/AM负载法测定胞浆钙离子浓度。结果:石杉碱甲能明显改善D-半乳糖诱致衰老小鼠学习记忆障碍,并明显降低脑组织NO含量,抑制NOS活性提高GSH-Px和SDH活性,降低胞浆钙离子水平(P<0.01,P<0.05)。结论:石杉碱甲具有提高衰老小鼠脑抗氧化能力和调节胞浆钙离子稳态的作用,可能是其改善学习记忆障碍和脑神经细胞保护作用的基础。     

石杉碱甲胶囊,片剂双盲治疗增龄相关记忆障碍疗效比较

目的:比较石杉碱甲胶囊、片剂治疗增龄相关记忆障碍的效果.方法;对60例年龄≥60周岁增龄相关记忆障碍进行双盲观察,疗程2mo.结果:35例石杉碱甲胶囊治疗前后MQ值为87.34±11.95及99.09±14.76;25例石杉减甲片剂治疗前后MQ值分别为90.88±12.22及104.72±13.21,治疗前后均有极显著差异.胶囊与片剂总有效率分别为51.42%与64%,无明显差异.未见严重不良反应.结论:石杉碱甲胺囊及石杉碱甲片剂均系安全有效的改善记忆(及认知)功能的药物.     

石杉碱甲的研究现状

目的:介绍近几年石杉碱甲药理作用的研究进展.方法:查阅相关文献并进行综合分析.结果:石杉碱甲不仅通过抑制胆碱酯酶活性,还可以通过影响自由基系统,降低生长抑素、细胞内[Ca2 ]、谷氨酸含量,提高钙调蛋白(CaM)和钙调蛋白的信使核糖核酸(CaMmRNA)表达水平等多种药理机制,提高认知功能和学习记忆能力.结论:石杉碱甲有可能成为理想的抗衰老药物之一.     

合成左旋石杉碱甲对胆碱酯酶活性和小鼠水迷宫操作的作用

目的：比较合成和天然礤旋右杉碱甲（Ｈｕｐ Ａ）对胆碱酯酶的抑制作用以及对东莨菪碱所致记忆障碍的改善作用。方法：比色法用于测定胆碱酯酶活性，小鼠水迷宫用于评价促智作用。结果：合成ＨｕｐＡ抑制大鼠皮层和红细胞膜乙酰胆碱脂酶的ＩＣ５０值分别为６４．７（５２．６－７９．５），５３．９（４３．６－６６．６）ｎｍｏｌ·Ｌ＾－１，抑制大鼠血清丁酰胆碱酯酶的ＩＣ５０为５３．６（４４．９－０．４８）μｍｏｌ·Ｌ＾－     

Nicotine-alcohol interactions and cognitive function in rats

Nicotine and ethanol are the most widely abused drugs in the world. They are very often used and abused together. However, little is known about the functional interaction of nicotine and ethanol. The current project studied the interactive effects of nicotine and ethanol on working memory in the eight-arm radial maze. Adult female rats were trained on a radial arm maze for 18 sessions to reach asymptotic levels of choice accuracy. During the maintenance phase of radial arm maze testing, which indexed working memory function, the rats were injected with nicotine (0, 0.15, 0.3, 0.6, and 1.2 mg/kg sc, 20 min before testing) with and without ethanol pretreatment (0 or 1.5 g/kg, 16% v/v ip, 30 min before testing). All animals received the treatments in a counterbalanced order with at least 1 week between treatments. Higher doses of nicotine had a significant interaction with ethanol in terms of radial arm maze choice accuracy. Nicotine plus ethanol coadministration precipitated a significant choice accuracy impairment at doses that when given alone had no effect on performance. At the lower dose range of nicotine, ethanol coadministration eliminated the nicotine-induced memory improvement. No significant effects were seen with either nicotine or ethanol treatment or their interaction on response latency in the radial arm maze. The nicotine-ethanol interactive effects on memory were compared with the interaction of their well-characterized hypothermic effects. Nicotine and alcohol, when injected separately or in combination, induced hypothermia with no significant interactive effect. This study found that ethanol blocked low-dose nicotine-induced memory improvement and precipitated memory impairment with high-dose nicotine treatment. This interaction may be an important consideration for nicotine and ethanol coabuse and the possible therapeutic use of nicotinic drugs for memory dysfunction.     

Coadministration of huperzine A and ligustrazine phosphate effectively reverses scopolamine-induced amnesia in rats

In the present study, whether coadministration of huperzine A (HA) and ligustrazine phosphate (LP) could effectively improve the memory deficits in association with ameliorating cholinergic impairment and oxidative stress in the scopolamine-induced amnesia rats was assessed. The effects of treatment with Coa [HA (0.14 mg/kg, i.g.) and LP (110 mg/kg, i.g.)] on amnesia were investigated in Morris water maze. Furthermore, the effects on the activities of acetylcholinesterase (AChE) and antioxidant enzymes within the cerebral cortex and hippocampus were evaluated, and the lipid peroxidation product malondialdehyde (MDA) was also analyzed. As a result, coadministration of HA and LP for 10 consecutive days could markedly reverse the scopolamine-induced learning and memory impairment determined by the Morris water maze test. Moreover, AChE activity was significantly inhibited, and superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities were significantly increased with a remarkable reduction in the level of MDA. In conclusion, coadministration of HA and LP effectively prevented cholinergic impairment and oxidative damage, thereby resulting in improvement of spatial learning memory in rats induced by scopolamine. The results suggested that coadministration of HA and LP might offer a novel poly-therapeutic drug regimen for preventing Alzheimer's disease (AD).     

The effects of d-cycloserine and MK-801 on the performance of rats in two spatial learning and memory tasks

The present study was undertaken to investigate the effects of modulation of the (NMDA) receptor on learning and memory. Thus, the performance of rats treated with d-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats. d-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However, d-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg d-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations.     

Estrogen and NMDA receptor antagonism: effects upon reference and working memory.

Since both estrogen and NMDA receptor antagonists act on the hippocampus CA1 region and behaviorally affect hippocampal memory tasks, we examined how estrogen depletion (ovariectomy) and NMDA receptor antagonism interact upon spatial memory of the mouse. After ovariectomy or sham operation, mice were given a 2-week recovery before behavioral tests began under the influence of vehicle or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP 2, 5 and 10 mg/kg) intraperitoneal injections. CPP is a competitive, full NMDA receptor antagonist. Spatial reference memory was tested by the water maze, spatial working memory was tested by the radial arm maze, while overall locomotive activity was monitored by the Y-maze. Results from the water maze and the Y-maze did not show any spatial reference memory or activity differences between sham-operated and ovariectomized mice. The radial arm maze, however, highlighted some working memory differences between intact and ovariectomized mice. CPP treatment impaired dose dependently--the performance of ovariectomy and sham-operated mice equally on both water maze and radial arm maze, while the drug had no effect on Y-maze performance. These results suggest that short term estrogen deprivation has no effect upon spatial-reference memory, while it impairs spatial working memory. This effect is probably not mediated by NMDA receptors.     

Anti-acetylcholinesterase and anti-amnesic activities of a pregnane glycoside, cynatroside B, from Cynanchum atratum

We previously reported that seven pregnane glycosides including cynatroside B isolated from the roots of Cynanchum atratum significantly inhibited acetylcholinesterase (AChE) activity. In the present study, we have characterized the mode of AChE inhibition of cynatroside B, the most potent of these isolated pregnane glycoside inhibitors. We have also examined the anti-amnesic activity of cynatroside B. Cynatroside B inhibited AChE activity in a dose-dependent manner and its IC50 value was 3.6 microM. The mode of AChE inhibition by cynatroside B was reversible and non-competitive in nature. Moreover, cynatroside B (1.0 mg/kg body weight i.p.) significantly ameliorated memory impairments induced in mice by scopolamine (1.0 mg/kg body weight s.c.) as measured in the passive avoidance and the Morris water maze tests. We suggest, therefore, that cynatroside B has both anti-AChE and anti-amnesic activities that may ultimately hold significant therapeutic value in alleviating certain memory impairments observed in Alzheimer's disease.     

石杉碱甲和乙促进小鼠的空间辨别学习和记忆

石杉碱甲和乙是从石杉科石杉属植物蛇足石杉[Huperzia scrrata(Thunb.)Trev.]中分得的二个新生物碱。“Y”迷宫实验表明,ip Hup-A 0.075～0.125 mg/kg或Hup-B 0.4～0.8mg/kg,均能明显促进小鼠的空间辨别学习,并能显著预防CO₂产生的短时识别障碍,促进记忆保持和记忆再现。ig Hup-A 0.1～0.3 mg/kg或Hup-B 0.8 mg/kg也有促进学习的作用。促进作用Hup-A>Phys>Hup-B。剂量与效应曲线呈倒U型。     

The use of a silymarin/phospholipid compound as a fetoprotectant from ethanol-induced behavioral deficits

We have replicated an earlier study in which silymarin/phytosome appeared to prevent deficits in social memory function in male rats exposed in utero to ethanol (EtOH).1 Female rats were included in the current study as well as a second behavioral test, the radial arm maze. Pregnant Sprague-Dawley rats were provided with liquid diets containing 35% ethanol derived calories (EDC). The silybin/phospholipid compound (SI) was co-administered with EtOH to the experimental group. The offspring were tested at age 90 days on the social recognition task and at 75 days on the radial arm maze. Female EtOH-exposed offspring performed more poorly on the radial arm maze than did female EtOH/SI offspring and the offspring of female controls. Male EtOH-exposed offspring were less able to form social memories than the male EtOH/SI offspring and the offspring of male controls.     

Effects of Ginkgo biloba administered after spatial learning on water maze and radial arm maze performance in young adult rats

Ginkgo biloba is reported to improve learning and memory in animals. However, many studies do not directly test the effects of Ginkgo on memory because the drug is administered during the learning phase of the experiments. In this study, we examined the effect of 10 mg/kg, 20 mg/kg, or 40 mg/kg G. biloba extract on spatial memory by administering the drug in the interval between training and testing. Rats were tested for long-term reference memory retention in the radial arm maze and in the Morris water maze during daily probe trials in which the hidden platform was removed. G. biloba had no effect on reference memory in either the water maze or radial arm maze. To test short-term working spatial memory using the radial arm maze, animals were removed after receiving the reward from 4 of the 8 arms and were returned to complete the maze 2 h later. While Ginkgo had no effect on working memory, over time animals exposed to Ginkgo learned task better than control animals. Thus, Ginkgo appears to enhance neither short-term working memory nor long-term reference memory, but it may promote learning of spatial information.     

Nicotine impairs acquisition of radial maze performance in rats

The effects of nicotine (NIC) and scopolamine (SCOP) on radial maze acquisition were examined using an 8-arm radial maze. In Experiment 1, food-deprived Sprague-Dawley rats were trained to eat food pellets located at the ends of each arm of the radial maze without repeating arm choices. Both NIC (0.45 mg/kg, SC) and SCOP (0.25 mg/kg, IP) impaired acquisition when they were administered before, but not after the daily training sessions. Experiment 2 examined the effect of nicotine on working and reference memory in rats trained to a criterion of 3 correct choices out of the first 4 choices with only 4 of the 8 arms baited. NIC (0.1-0.45 mg/kg) had no effect on working memory (reentry into baited arms) or reference memory (entry into unbaited arms) errors. It is concluded that NIC impairs processes involved in the acquisition but not maintenance of radial maze performance. Neither NIC nor SCOP affects post-training consolidation processes.