Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn

The high affinity binding sites for serotonin and benzodiazepine in the frontal cortex, for dopamine in the striatum and muscarinic cholinergic receptors in the hippocampus were investigated in the brains of Charles Foster rats treated for 3 days. Transfer latency on elevated plus maze (TL), passive and active avoidance behaviour (PA and AA) and electroconvulsive shock (ECS) induced amnesia were also studied. Pilot studies indicated that single dose administration of Indian Hypericum perforatum (IHp) had little or no acute behavioural effects and hence the extract of IHp was administered orally at two dose levels (100 and 200 mg/kg, p.o.) once daily for 3 consecutive days, while piracetam (500 mg/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard nootropic agent. Control rats were treated with an equal volume of vehicle (0.3% carboxymethyl cellulose). The results indicate that IHp treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and an increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Preliminary pharmacological studies with IHp extract indicate the presence of two major behavioural actions, namely, antidepressant and anxiolytic. The present findings tend to elucidate the mechanism of earlier observations, the downregulation of the dopamine D2 receptor being consonant with anxiolytic and the upregulation of 5-HT2A and BDZ receptors being consonant with antidepressant activity. Piracetam when given alone, shortened the TL on days 1, 2 and 9 day and also antagonized the amnesic effects of ECS on the TL significantly, whereas IHp antagonized the amnesia produced by ECS. IHp had no significant effect per se on the retention of the PA in rats but produced a significant reversal of ECS induced PA retention deficit. Piracetam showed a significant facilitatory effect per se on PA retention and also reversed the ECS induced impaired PA retention. In the AA test, piracetam facilitated the acquisition and retention of AA in rats but IHp had no effect per se. Both the doses of IHp and piracetam significantly attenuated the ECS induced impaired retention of AA. These results indicate a possible nootropic action of IHp in amnesic animals, which was comparable qualitatively to piracetam.     

Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats

Aim of the Study

Centella asiatica has a reputation to restore declining cognitive function in traditional medicine. To date, only a few compounds that show enhancing learning and memory properties are available. Therefore, the present study investigates the effects of for acute administration of asiatic acid (A-A) isolated from Centella asiatica administration on memory and learning in male Spraque-Dawley rats.

Materials and Methods

4-5 weeks Spraque-Dawley rats were administered with concentration 1, 3, 5, 10, 30 mg/kg of A-A, baclofen, scopolamine and saline intra peritoneally and were evaluated for passive avoidance (PA), active avoidance (AA) and changes in blood pressure (BP).

Results

Treatment 30 mg/kg of A-A resulted in significantly dose-dependently improved memory, with increased retention latency to enter difference compartment in PA test compared to baclofen, saline and scopolamine. Furthermore, 30 mg/kg of A-A was significantly higher on learning abilities on 1st day but there was no significantly difference on avoidance memory ability after 7 days of retention. Low reading in blood pressure dose-dependent significantly difference was observed in the 30 mg/kg of A-A group compared to saline group.

Conclusions

Administration A-A facilitated PA and AA on memory and learning and but had no effect on active avoidance on memory. Hence, may serve useful memory and learning with less effect in blood pressure in promoting memory and learning increases.     

苁蓉总苷对小鼠学习记忆障碍的影响

目的观察苁蓉总苷对东莨菪碱所致的小鼠学习记忆获得障碍及亚硝酸钠所致小鼠学习记忆巩固障碍的影响.方法使用跳台法观察小鼠的学习记忆功能.连续灌胃给予苁蓉总苷30d,于实验的第29天训练,第30天测试,记录各动物的首次跳台潜伏期及5 min内的错误次数.东莨菪碱模型于训练前15 min腹腔注射东莨菪碱,而亚硝酸钠模型于训练后立即皮下注射亚硝酸钠.结果与东莨菪碱模型组比较,苁蓉总苷400、200 mg/kg组及脑复康组潜伏期均明显延长,错误次数明显减少;苁蓉总苷100 mg/kg组潜伏期亦明显延长,但错误次数只有一定程度的减少.与亚硝酸钠模型组比较,苁蓉总苷400、200 mg/kg组潜伏期均明显延长,错误次数有一定程度的减少,但无统计学意义;苁蓉总苷 100 mg/kg组潜伏期及错误次数只有一定程度的改善;脑复康组潜伏期明显延长,错误次数显著减少.结论苁蓉总苷对东莨菪碱所致的小鼠学习记忆获得障碍及亚硝酸钠所致小鼠学习记忆巩固障碍均有明显的改善作用.     

神经营养因子样土党参多糖促进小鼠学习记忆作用的实验研究

目的探讨具有神经营养因子(NGF)样活性的土党参多糖对小鼠学习记忆的作用效果。方法以东莨菪碱、亚硝酸钠、乙醇分别造成小鼠学习记忆获得障碍、记忆巩固障碍和记忆再现障碍,采用跳台法、Y水迷宫法和暗箱法进行观察。结果 土党参粗多糖(150 mg/kg和300 mg/kg)、土党参多糖纯组分(150 mg/kg和300 mg/kg)及脑复康(500 mg/kg)均可使小鼠逃避伤害刺激的反应速度加快,错误次数明显减少,遭电击时间缩短(与模型组比较,P<0.01或P<0.05),两药的效果相近(P>0.05)。结论 具有NGF样活性的土党参多糖具有改善小鼠学习记忆能力的作用。     

Effects of standardized ginseng extract on learning, memory and physical capabilities

Standardized ginseng extract (G115, Pharmaton, Lugano) was administered orally at doses of 3, 10, 30, 100 and 300 mg/kg for 10 days as ten rats were used with each dose. With the "shuttle-box" method for active avoidance most pronounced effect on learning and memory was obtained by the dose of 10 mg/kg. With the "step-down" method for passive avoidance the dose of 30 mg/kg significantly improved retention. In the staircase maze training with positive (alimentary) reinforcement only the dose of 10 mg/kg significantly improved learning and memory. The dose of 100 mg/kg greatly increased the locomotor activity of mice. The results show that ginseng at appropriate doses improves learning, memory and physical capabilities. Bell-shaped dose-effect curves, reported with other nootropic drugs, were obtained.     

Schizandrin reverses memory impairment in rats

The present study investigated the effect of schizandrin, a component of the fruit of Schizandra chinesis Baill (Fructus Schizandrae), on memory impairment in rats. Scopolamine (0.5 mg/kg, i.p.), a non-selective muscarinic receptor antagonist, markedly impaired spatial memory in an eight-arm radial maze. A higher dose of scopolamine (3 mg/kg, i.p.) also impaired the passive avoidance response. Schizandrin (1 and 10 mg/kg, p.o.) significantly reversed the scopolamine-induced impairment of spatial memory. Similarly, schizandrin (1 mg/kg, p.o.) significantly reversed the scopolamine-induced impairment of the passive avoidance response. Moreover, in mice, schizandrin (1 and 10 mg/kg, p.o.) enhanced tremors induced by oxotremorine, a muscarinic M(1) receptor agonist. Taken together these findings suggest that schizandrin reverses scopolamine-induced memory impairment, in part, by enhancing cholinergic function, and that schizandrin might be useful for treating memory deficits.     

Effects of Hypericum perforatum extract on diabetes‐induced learning and memory impairment in rats

Cognitive impairment occurs in diabetes mellitus. Hypericum perforatum has been used in folk medicine to improve mental performance. Here it is hypothesized that chronic treatment with an extract of Hypericum perforatum (6, 12 and 25 mg/kg, p.o.) would have effects on passive avoidance learning (PAL) and memory in control and streptozotocin‐induced diabetic rats. Treatments were begun at the onset of hyperglycaemia. PAL was assessed 30 days later. A retention test was done 24 h after training. At the end, the animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. Hypericum treatment (12 and 25 mg/kg) improved learning and memory in control rats and reversed learning and memory deficits in diabetic rats. A dose of 6 mg/kg did not affect cognitive function. Hypericum administration did not alter the body weight and plasma glucose levels. Antioxidant properties and cholinergic facilitatory effects of Hypericum may be involved in its nootropic effects. These results show that Hypericum perforatum prevented the deleterious effects of diabetes on PAL and memory. As Hypericum would be free of major side effects compared with other nootropic medications, it may provide a new potential alternative for demented diabetic patients. Copyright © 2010 John Wiley & Sons, Ltd.     

膜滤工艺对安神补脑液药效的影响

目的 研究膜滤工艺对安神补脑液有效性的影响.方法用小鼠自主活动、戊巴比妥钠阈剂量所致小鼠睡眠时间实验、戊巴比妥钠阁下催眠剂量试验和药物致小鼠惊厥实验,观察安神补脑液的镇静催眠作用;选择小鼠记忆获得障碍模型、小鼠记忆巩固障碍模型和小鼠记忆再现障碍模型,观察安神补脑液对记忆功能的改善作用;用小鼠常压缺氧、小鼠断头缺氧及游泳实验观察安神补脑液的抗缺氧、抗疲劳作用.结果膜滤安神补脑液可减少小鼠自主活动次数,延长戊巴比妥钠所致小鼠的睡眠时间,增加戊巴比妥钠阈下催眠剂量小鼠睡眠个数;对小鼠记忆获得障碍和记忆再现障碍均有明显的改善作用;同时,能增加小鼠常压缺氧的存活时间,并延长小鼠断头后的呼吸时间和喘息次数.结论膜滤安神补脑液具有镇静催眠、改善记忆和抗缺氧作用.     

Neuropharmacological profile of Eclipta alba (Linn.) Hassk

The present study deals with the investigation of standardized and phytochemically evaluated aqueous and hydroalcoholic extracts of the plant Eclipta alba for sedative, muscle-relaxant, anxiolytic, nootropic and anti-stress activities. The hydrolyzed fraction of the aqueous extract was also subjected to similar studies in rats. The aqueous and hydroalcoholic extracts were administered in a dose of 150 and 300 mg/kg, p.o., while the hydrolyzed fraction was administered in a dose of 30 mg/kg, p.o. The findings indicated nootropic activity of the aqueous extract (300 mg/kg, p.o.) and its hydrolyzed fraction (30 mg/kg, p.o.). The effect of the extracts on stress-induced alterations was evaluated. The aqueous extract and the hydrolyzed fraction provided protection against cold restraint induced gastric ulcer formation and also normalized the white blood cell count in the milk induced leukocytosis challenge model. The hydroalcoholic extract on the other hand demonstrated a significant effect only in the milk induced leukocytosis challenge model. The results point towards the potential neuropharmacological activity of the plant Eclipta alba as a nootropic and also having the property of attenuating stress induced alterations. Further neurochemical investigations can unravel the mechanism of action of the plant drug with respect to nootropic activity and help to establish the plant in the armamentarium of nootropic agents.     

Effect of Evolvulus alsinoides Linn. on learning behavior and memory enhancement activity in rodents

In the Ayurvedic system of medicine, the whole herb of ‘Shankhpushpi’ has been employed clinically for centuries for its memory potentiating, anxiolytic and tranquilizing properties. The present study was undertaken to investigate the effects of Evolvulus alsinoides (EA), considered as Shankhpushpi on learning and memory in rodents. Nootropic activity using Cook and Weidley's pole climbing apparatus, passive avoidance paradigms and active avoidance tests were used to test learning and memory. The ethanol extract of EA and its ethyl acetate and aqueous fractions were evaluated for their memory enhancing properties. Two doses (100 and 200 mg/kg p.o.) of the ethanol extract and ethyl acetate and aqueous fractions were administered in separate groups of animals. Both doses of all the extracts of EA significantly improved learning and memory in rats. Furthermore, these doses significantly reversed the amnesia induced by scopolamine (0.3 mg/kg i.p.). Nootropic activity was compared using piracetam as the standard. EA also exhibited potent memory enhancing effects in the step‐down and shuttle‐box avoidance paradigms. Copyright © 2009 John Wiley & Sons, Ltd.     

党参益智作用研究

用小鼠跳台法和大鼠操作式条件反应——固定比率操作观察了党参20％乙醇提取物对学习记忆的影响,结果表明党参可拮抗东莨菪碱造成的小鼠记忆获得不良,改善亚硝酸钠造成的小鼠记忆巩固障碍及40％乙醇造成的小鼠记忆再现缺损,部分对抗东莨菪碱对大鼠固定比率操作的抑制。党参进一步分离的正丁醇部分可以重现上述作用。党参正丁醇部分对M胆碱能受体无亲和力,但可使中枢M胆碱受体密度显著增高。但它既不能对抗东莨菪碱所致小鼠大脑皮层及海马Ach含量的降低,其本身也不能提高皮层和海马的Ach含量。以上结果提示党参对学习记忆确有改善作用,胆碱能通路可能是其发生作用的一个重要方面。     

Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine‐induced learning and memory impairment in mice

Rg1 and Rb1 are two major active compounds of ginseng that facilitate learning and memory. The present study aimed to compare the nootropic effects of Rg1 and Rb1 in a scopolamine induced dementia mice model. After 6 and 12 mg/kg of Rg1 and Rb1 intraperitoneal administration to mice for 7 days, their effects were assessed using the step‐down passive avoidance (SD) and the Morris water maze (MWM) tests, the acetylcholinesterase (AChE) activity, acetylcholine (ACh) content and serotonin (5‐HT) level in the hippocampus were analysed after SD and MWM tests. The results showed that Rg1 and Rb1 ameliorated cognition‐deficiency in mice with dementia. Rg1 showed stronger effects than Rb1 on escape acquisition in MWM. Both Rg1 and Rb1 increased ACh levels in the hippocampus, but Rg1 inhibited AChE activity while Rb1 had no effect on AChE activity. Both Rg1 and Rb1 inhibited the decrease of 5‐HT induced by scopolamine, but Rb1 was more active than the same dose of Rg1. These results demonstrate that multiple administrations of Rg1 and Rb1 are effective in improving memory deficiency induced by scopolamine. Rg1 appears to be more potent than Rb1 in improving acquisition impairment, and the two ginsenosides may act through different mechanisms. Copyright © 2010 John Wiley & Sons, Ltd.     

益智丸对小鼠记忆、脑内SOD、MDA及免疫功能的影响

采用跳台和避暗法实验对益智丸进行研究,结果表明益智丸100mg/kg连续ig给药15天,能明显促进正常小鼠的记忆功能;100,200,500mg/kg连续ig给药5天,能明显对抗东莨菪碱、亚硝酸钠及乙醇引起的记忆障碍;200,500mg/kg连续ig给药41天,明显改善D半乳糖所致的亚急性衰老小鼠的记忆损害,并升高其脑内SOD活力,降低MDA含量,抑制其胸腺指数的下降;另外,益智丸还能升高环磷酰胺诱导的免疫低下小鼠炭粒廓清指数及溶血素抗体生成量,增强氢化泼尼松抑制的细胞免疫反应。     

Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer's disease and perturbed central cholinergic markers of cognition in rats

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.     

Effects of yizhi pills on memory, superoxide dismutase and malondialdehyde of brain and immunity in mice]

Passive avoidance tests have shown that Yizhi Pills (YZ) markedly improve the memory of normal mice at a dose of 100 mg/kg after oral administration for fifteen days, and significantly reverse the scopolamine, NaNO2 and EtOH-induced disruptions of memory retention in mice at doses of 100, 200, 500 mg/kg after oral administration for five days. In aged mice induced by D-galactose, YZ also significantly improve the impaired memory, increase the activity of SOD and decrease the content of MDA in brain. All these effects were observed at doses of 200, 500 mg/kg after oral administration for forty-one days. YZ significantly promote blood carbon particle clearance, enhance hemolysin antibody in immunodepressed mice induced by cyclophosphamide, and increase earswelling in immunodepressed mice induced by prednisolonum.     

Panax ginseng extract improves scopolamine-induced deficits in working memory performance in the T-maze delayed alternation task in rats

The effects of Panax ginseng water extract on spatial working memory disruption induced by scopolamine were examined using a T-maze delayed alternation task in rats. Scopolamine (0.025–0.1 mg/kg, i.p.) dose-dependently impaired the maze performance, and physostigmine (0.4 mg/kg) significantly reversed the scopolamine (0.1 mg/kg)-induced performance deficits. Ginseng extract (0.5–4.0 g dried root/kg) orally administered 60 min before testing dose-dependently improved the maze performance disrupted by scopolamine (0.1 mg/kg). Ginseng extract given for 7 days in drinking water (2.0 and 4.0 g/kg/day) also exhibited dose-dependent reversal of the scopolamine-induced performance deficits. These data indicate the beneficial effects of ginseng extract on spatial working memory in rats.     

Procyanidins extracted from the lotus seedpod ameliorate scopolamine‐induced memory impairment in mice

The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the learning and memory impairments induced by scopolamine (1 mg/kg, i.p.) in mice. The capacities of memory and learning were evaluated by the Morris water maze and the step‐down avoidance test. LSPC (50, 100, 150 mg/kg BW, p.o.) significantly reversed scopolamine‐induced learning and memory impairments in the Morris water maze test, as evaluated by shortened escape latency and swimming distance. In the step‐down avoidance test, LSPC (50, 100, 150 mg/kg BW, p.o.) treatment significantly reduced the number of errors and shortened latency compared with that of scopolamine. In addition, LSPC was also found to inhibit acetyl cholinesterase (AChE) activity. These results of this study suggest that LSPC may play a useful role in the treatment of cognitive impairment caused by AD and aging. Copyright © 2009 John Wiley & Sons, Ltd.     

文冠果果壳提取物对学习记忆障碍的改善作用

目的研究文冠果果壳乙醇提取物、总皂苷及ST-n-2对学习记忆障碍的影响,并初步探讨其作用机制。方法采用跳台法观察东莨菪碱和亚硝酸钠所致学习记忆障碍小鼠的学习记忆能力,八臂放射状迷路法观察( )-MK-801致学习记忆障碍大鼠的学习记忆能力。结果文冠果果壳乙醇提取物、总皂苷及ST-n-2均显著改善东莨菪碱所致的记忆获得障碍和亚硝酸钠所致的记忆巩固障碍,文冠果果壳乙醇提取物显著改善( )-MK-801所致的工作记忆和参照记忆障碍。结论文冠果果壳乙醇提取物、总皂苷及ST-n-2对学习记忆障碍均有显著改善作用,其作用机制可能与增强中枢胆碱能神经系统及谷氨酸能神经系统功能、抗脑组织耗氧损伤有关;总皂苷是文冠果果壳改善记忆障碍的有效部位,ST-n-2是其主要有效成分之一。     

中药调神口服液治疗儿童多动症临床与实验研究

用中药调神口服液治疗儿童多动症１００例，治疗后行为评分明显降低，注意力涣散好转，学习成绩提高，总有效率达９４％。动物实验结果表明：该药有使正常小鼠自发活动减少的趋势，可显著减少东莨菪碱多动模型小鼠的自发活动；增强正常小鼠的学习记忆功能；对东莨菪碱、亚硝酸钠、乙醇三种记忆障碍模型小鼠的学习记忆功能均有不同程度改善，从而提示该药治疗本病的机理，可能与改善中枢神经系统胆碱能神经突触的信息传递功能，提高脑组织的耐缺氧能力有关。     

Petroleum ether extract of Cnidium monnieri ameliorated scopolamine-induced amnesia through adrenal gland-mediated mechanism in male rats

AIM: Our previous study indicated petroleum ether layer of Cnidium monnieri L. Cuss. (CM) and its ingredient osthole could alleviate scopolamine-induced amnesia in female rats. MATERIALS AND METHODS: Hence, this study was desired to investigate the mechanism of the ameliorating effects of petroleum ether layer of CM on the performance impairment of inhibitory avoidance task and Morris water maze induced by scopolamine in male rats. RESULTS: CM at 0.1-0.6g/kg orally administered 60 min before the training trial ameliorated the scopolamine-induced performance impairment on inhibitory avoidance learning and water maze in male rats. Only adrenalectomy but not peripheral cholinergic antagonist scopolamine methylbromide and catecholaminergic neurotoxin 6-hydroxydopamine blocked the ameliorating effects of CM on scopolamine-induced performance impairment in rats. CONCLUSION: Therefore, we demonstrated that the ameliorating effects of CM on scopolamine-induced performance impairment may be related to activating the adrenal gland and central acetylcholingeric neuron, instead of peripheral nervous system.