Cognitive improving and cerebral protective effects of acylated oligosaccharides in Polygala tenuifolia

We studied the cognitive improving and cerebral protective constituents in the roots of Polygala tenuifolia Willdenow, a well-known Chinese traditional medicine prescribed for amnesia, neurasthenia, palpitation, noctural emission and insomnia. Tenuifoliside B (1), which is one of the acylated oligosaccharides in the roots of P. tenuifolia, showed the cerebral protective effect on potassium cyanide (KCN)-induced anoxia in mice, widely used as an animal model for cerebrovascular disease, and also had an ameliorative effect on the scopolamine-induced impairment of performance in passive avoidance task in rats. Compound 1 significantly enhanced oxotremorine-induced tremors in mice, suggesting that it ameliorated the scopolamine-induced impairment of passive avoidance response by enhancing the cholinergic system. These findings show that compound 1 has cognitive improving and cerebral protective effects.     

腺苷A1受体阻断剂对学习记忆的影响及机制分析腺苷A1受体阻断剂对学习记忆的影响及机制分析

目的探讨腺苷A₁受体阻断剂对学习记忆的影响及其与胆碱能、氨基酸能神经的关系。方法采用避暗实验、分光光度法和HPLC法,观察腺苷A₁受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对东莨菪碱(Scop)、2-氨基-5-磷戊酸(AP₅)致小鼠记忆障碍及脑胆碱酯酶(AChE)活性、氨基酸水平的影响。结果DPCPX可显著改善Scop致记忆障碍,但对AP₅致记忆障碍无影响；在体内外高剂量DPCPX可显著抑制小鼠脑AChE活性；DPCPX icv可显著升高小鼠脑Glu和Asp含量,降低GABA含量,使脑内Glu/GABA比值显著升高。结论腺苷A₁受体特异性阻断剂DPCPX可显著改善Scop而不能改善AP₅致记忆障碍,在高剂量时可影响脑AChE活性和脑氨基酸水平、升高脑内Glu/GABA比值。     

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC₅₀ value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.     

Influence of benzodiazepine binding site ligands on fear-conditioned contextual memory

Eight compounds that bind to the benzodiazepine binding site on the gamma-amino butyric acid(A) (GABA(A)) receptor were assessed for their influence on contextual memory, an aspect of memory affected in various cognitive disorders including Alzheimer's disease. Using a Pavlovian fear-conditioning paradigm, each ligand was evaluated in C57Bl/6 mice in regards to its direct affect on contextual memory and whether the ligand could attenuate scopolamine-induced contextual memory impairment. Of the eight ligands tested, one impaired contextual memory (agonist), six attenuated scopolamine-induced contextual memory impairment (inverse agonists), and one antagonized the ability of an inverse agonist to attenuate scopolamine-induced contextual memory impairment. Hence, further demonstrating the bi-directional influence benzodiazepine binding site ligands are able to exert on memory modulation. This study serves as an initial starting point in the development of pharmacological tools to be used in deciphering how GABA(A) receptors influence contextual memory.     

Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice

Eucommia ulmoides Oliv. Bark (EUE) is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia as well as to promote longevity. In this study, we tested the effects of EUE aqueous extract in graded doses to protect and enhance cognition in scopolamine-induced learning and memory impairments in mice. EUE significantly improved the impairment of short-term or working memory induced by scopolamine in the Y-maze and significantly reversed learning and memory deficits in mice as measured by the passive avoidance and Morris water maze tests. One day after the last trial session of the Morris water maze test (probe trial session), EUE dramatically increased the latency time in the target quadrant in a dose-dependent manner. Furthermore, EUE significantly inhibited acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus and frontal cortex in a dose-dependent manner. EUE also markedly increased brain-derived neurotrophic factor (BDNF) and phosphorylation of cAMP element binding protein (CREB) in the hippocampus of scopolamine-induced mice. Based on these findings, we suggest that EUE may be useful for the treatment of cognitive deficits, and that the beneficial effects of EUE are mediated, in part, by cholinergic signaling enhancement and/or protection.     

Effect of Polygala tenuifolia root extract on scopolamine-induced impairment of rat spatial cognition in an eight-arm radial maze task

The effects of Polygala tenuifolia root fractions and the acyl groups of its constituents on the retrieval process of spatial cognition in rats were studied using an eight-arm radial maze task. Oral administration of a precipitate fraction (PTB) obtained by concentration of the n-BuOH-soluble portion from the extract of the roots significantly decreased the number of total errors (TEs) and that of working memory errors (WMEs) at doses of 100 mg/kg and 200 mg/kg. However, it caused no significant decrease in the number of reference memory errors (RMEs). In addition, the saponin-rich fraction (PTBM) obtained by purification of PTB also showed significant decreases in TEs and WMEs at a dose of 100 mg/kg. Among the cinnamic acid derivatives present as the acyl groups in the P. tenuifolia constituents, sinapic acid (SNPA) significantly decreased TEs and WMEs at doses of 10 to 100 mg/kg. These results indicated that P. tenuifolia extracts, PTB and PTBM, and SNPA had a beneficial effect on the memory impairment induced by dysfunction of the cholinergic system in the brain. The memory improvement in the scopolamine-induced memory impairment seen in the radial maze performance was due to improvement in the short-term memory. A contribution of some constituents other than SNPA to the memory improvement was also suggested.     

Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve scopolamine-induced memory impairment in mice.

Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to be more beneficial than other varieties of Maca on learning and memory in ovariectomized mice on the water finding test. The present study aimed to test two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and 1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and learning were evaluated using the water Morris maze and the step-down avoidance test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in brain were also determined. Both extracts of Black Maca significantly ameliorated the scopolamine-induced memory impairment as measured in both the water Morris maze and the step-down avoidance tests. Black Maca extracts inhibited AChE activity, whereas MAO activity was not affected. These results indicate that Black Maca improves scopolamine-induced memory deficits.     

Effects of systemic administration of beta-casomorphin-5 on learning and memory in mice

The effects of systemic administration of bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), a mu-opioid receptor agonist derived from milk beta-casein, on spontaneous alternation behavior in the Y-maze (spatial short-term memory) and step-down-type passive avoidance response (non-spatial long-term memory) were investigated in mice. Intraperitoneal (i.p.) administration of beta-casomorphin-5 (0.1-20 mg/kg) did not have a significant effect on either spontaneous alternation behavior or passive avoidance response. However, a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improved scopolamine (1 mg/kg, s.c.)-induced impairment of spontaneous alternation behavior and passive avoidance response. Pretreatment with intracerebroventricular injections of beta-funaltrexamine (a mu-opioid receptor antagonist, 0.1 microg/mouse) and naloxonazine (a mu(1)-opioid antagonist, 5 microg/mouse), which did not improve scopolamine-induced impairment, prevented the ameliorating effect of beta-casomorphin-5 on scopolamine-induced impairment of passive avoidance response. These results indicated that systemic administration of a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improves the disturbance of learning and memory resulting from cholinergic dysfunction through central mediation involving mu(1)-opioid receptors.     

Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice

The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.     

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).     

Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function

Rational

Inhibition of renin?Cangiotensin system (RAS) improves cognitive functions in hypertensive patients. However, role of AT1 and AT2 receptors in memory impairment due to cholinergic hypofunction is unexplored.

Objective

This study investigated the role of AT1 and AT2 receptors in cerebral blood flow (CBF), cholinergic neurotransmission, and cerebral energy metabolism in scopolamine-induced amnesic mice.

Methods

Scopolamine was given to male Swiss albino mice to induce memory impairment tested in passive avoidance and Morris water maze tests after a weeklong administration of blocker of AT1 receptor, candesartan, and AT2 receptor, PD123, 319. CBF was measured by laser Doppler flowmetry. Biochemical and molecular studies were done in cortex and hippocampus of mice brain.

Results

Scopolamine caused memory impairment, reduced CBF, acetylcholine (ACh) level, elevated acetylcholinesterase (AChE) activity, and malondialdehyde (MDA). Administration of vehicle had no significant effect on any parameter in comparison to control. Candesartan prevented scopolamine-induced amnesia, restored CBF and ACh level, and decreased AChE activity and MDA level. In contrast, PD123, 319 was not effective. However, the effect of AT1 receptor blocker on memory, CBF, ACh level, and oxidative stress was blunted by concomitant blockade of AT2 receptor. Angiotensin-converting enzyme (ACE) activity, ATP level, and mRNA expression of AT1, AT2, and ACE remained unaltered.

Conclusion

The study suggests that activation of AT1 receptors appears to be involved in the scopolamine-induced amnesia and that AT2 receptors contribute to the beneficial effects of candesartan. Theses finding corroborated the number of clinical studies that RAS inhibition in hypertensive patients could be neuroprotective.     

9-(4-乙氧羰基苯氧基)-6,7-二甲氧基-1,2,3,4-四氢吖啶盐酸盐抑制自由基诱发鼠皮层神经元毒性及脑缺血损伤

目的考察9-(4-乙氧羰基苯氧基)-6,7-二甲氧基-1,2,3,4-四氢吖啶盐酸盐(EDT)对自由基致原代培养大鼠皮层神经毒及小鼠脑缺血损伤的影响。方法原代培养的鼠皮层神经细胞,用H₂O₂致自由基损伤模型,测定细胞内丙二醛(MDA)及超氧化物歧化酶(SOD)活性。结扎单侧颈总动脉及迷走神经造成小鼠慢性脑缺血模型,用跳台法研究EDT对记忆障碍的影响。同时,检测了大脑皮层形态学变化,脑匀浆内MDA,NO含量及SOD活力。结果在原代培养神经元,0.01～3 μmol·L^-1 EDT浓度依赖地抑制H₂O₂诱发的MDA生成及SOD活力降低。在小鼠脑缺血模型,EDT 2.5,5和10 mg·kg^-1 ig 5 d可显著改善脑缺血小鼠的记忆障碍,对抗脑内NO释放及MDA生成,增加SOD活力。结论EDT能有效对抗自由基诱发的神经元毒性及脑缺血损伤。     

Ameliorative effect of NC-1900, a new AVP4-9 analog,through vasopressin V1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze

The mechanism by which NC-1900, a new pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH(2) (AVP(4-9)) analog, improves spatial memory in rats using an eight-arm radial maze was examined. Even at very low doses (0.2 ng/kg for s.c., 1 microg/kg for p.o., 1 fg for i.c.v.) NC-1900 improved scopolamine-induced impairment of spatial memory. NC-1900 (1 ng/kg, s.c.) also improved impairment of spatial memory induced by pirenzepine, a muscarinic(1) (M(1)) receptor antagonist, and by KN-62, a Ca2+/calmodulin (CaM)-dependent protein kinase II inhibitor. [Pmp(1), Tyr(Me)(2)]-Arg(8)-vasopressin, a vasopressin(1A) (V(1A)) receptor antagonist, and nicardipine, L-type Ca2+ blocker, but not OPC-31260, a V(2) antagonist, suppressed the effect of NC-1900 on scopolamine-induced impairment of spatial memory. A microdialysis study showed that NC-1900 did not affect acetylcholine release in the ventral hippocampus (VH) of intact rats or of scopolamine-treated rats. NC-1900 (1 microM) increased [Ca2+](i) in the VH than in the dorsal hippocampus (DH). Pretreatment with nicardipine (1 microM) and Ca2+ -free conditions inhibited the NC-1900-induced [Ca2+](i) response in the VH. Whereas co-administration of NC-1900 (1 microM) and carbachol (500 microM) increased [Ca2+](i) in the VH. Moreover, nicardipine concentration-dependently inhibited the increase in [Ca2+](i) induced by the co-administration of NC-1900 and carbachol in the VH. These results suggest that NC-1900 activates the V(1A) receptor at the postsynaptic cholinergic nerve, and causes a transient influx of intracellular Ca2+ through L-type Ca2+ channels, to interact with the M(1) receptor. The activation of these Ca2+ -dependent processes induced by NC-1900 may be involved in the positive effect of NC-1900 on scopolamine-induced impairment of spatial memory.     

Acteoside of Callicarpa dichotoma attenuates scopolamine-induced memory impairments

We previously reported that ten phenylethanoid glycosides including acteoside isolated from the leaves and twigs of Callicarpa dichotoma significantly attenuated glutamate-induced neurotoxicity. In the present study, we examined anti-amnesic activity of acteoside using scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with acteoside (1.0, 2.5 mg/kg body weight) significantly mitigated scopolamine-induced memory deficits in the passive avoidance test. It is interesting to note that prolonged oral daily treatment of mice with much lower amount (0.1 mg/kg body weight) of acteoside for 10 d reversed the scopolamine-induced memory deficits. In the Morris water maze, prolonged oral treatment with acteoside (prolonged daily administration of 1.0 mg/kg body weight for 10 d) significantly ameliorated scopolamine-induced memory deficits showing the formation of long-term and/or short-term spatial memory. We suggest, therefore, that acteoside has anti-amnesic activity that may ultimately hold significant therapeutic value in alleviating certain memory impairment observed in Alzheimer's disease.     

三种大黄酚制剂改善脑缺血/再灌注小鼠记忆功能的实验筛选研究

目的研究大黄酚聚氰基丙烯酸丁酯纳米囊、大黄酚羟丙基-β-环糊精包合物、大黄酚脂质体对脑缺血/再灌注(I/R)小鼠记忆功能的保护作用,以期选出药效最佳的大黄酚制剂。方法采用小鼠脑I/R损伤模型,进行避暗、探索、跳台、穿梭实验,观察3种大黄酚制剂对小鼠记忆功能的保护作用;并对各剂量组血液中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力进行测定,以及小鼠断头缺氧后存活时间和脑指数的测定。结果 3种大黄酚制剂可明显改善脑I/R损伤所致的记忆障碍;提高SOD、GSH-Px活力,延长缺氧后存活时间和增加脑指数,以大黄酚脂质体的作用最为明显。结论 3种大黄酚制剂对脑I/R损伤小鼠记忆功能具有保护作用,以大黄酚脂质体的作用最佳。     

Vinpocetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats

Vinpocetine, vincamine, aniracetam, and Hydergine, compounds with purported cognition activating activity, were evaluated for their ability to prevent scopolamine-induced and hypoxia-induced impairment of passive avoidance retention (24 hr) in rats. Vinpocetine (peak effect dose [PED]= 200 mg/kg PO), aniracetam (PED = 100 mg/kg PO), vincamine (PED = 30 mg/kg PO), and Hydergine (PED = 1 mg/kg PO) prevented memory disruption by scopolamine. Vinpocetine (PED = 3 mg/kg PO) and aniracetam (PED = 30 mg/kg PO) were also effective in preventing disruption of passive avoidance retention impaired by 7% oxygen hypoxia. In contrast, Hydergine (0.05 to 3 mg/kg PO) and vincamine (0.3 to 100 mg/kg PO) were not effective against hypoxia-induced impairment. Hydergine at doses greater than 10 mg/kg PO markedly impaired motor function. In both tests the protection was dose-related for all test substances in an inverted U-shaped manner. Mecamylamine (1, 3, 10 mg/kg SC), (-)-nicotine (0.1 to 0.4 mg/kg SC), apovincaminic acid (1-400 mg/kg PO) and pemoline (1-100 mg/kg PO) did not protect against memory impairment induced by either procedure. These data support the view that vinpocetine, a compound chemically distinct from the pyrrolidinones, has a cognitive activating ability as defined in models of both scopolamine-induced and hypoxia-induced memory impairment in rats.     

Cognitive-enhancing activity of loganin isolated from <Emphasis Type="Italic">Cornus officinalis</Emphasis> in scopolamine-induced amnesic mice

We examined anti-amnesic activity of the methanolic extract of Cornus officinalis fruits (COT) and a major constituent, loganin using scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and the Morris water maze tests. Oral treatment of mice with COT (100 mg/kg body weight) and loganin (1 and 2 mg/kg body weight) significantly mitigated scopolamine-induced memory deficits in passive avoidance test. In the Morris water maze test, oral treatment of loganin significantly ameliorated scopolamine-induced memory deficits showing the formation of long-term and/or short-term spatial memory. Moreover, loganin (2 mg/kg body weight) significantly inhibited acetylcholinesterase activity by as much as 45% of control in the mouse hippocampus. These results indicate that loganin may exert antiamnesic activity in in vivo through acetylcholinesterase inhibition.     

蜕皮甾酮对小鼠学习记忆的促进作用

采用一次性训练被动回避性条件反应方法———跳台法,观察了蜕皮甾酮（Ｅｃｄｙｓｔｅｒｏｎｅ）对小鼠学习记忆功能的影响．结果表明,蜕皮甾酮可拮抗东莨菪碱造成的记忆获得障碍,改善环己酰亚胺造成的记忆巩固不良和３０％乙醇造成的记忆再现缺失．蜕皮甾酮还具有抗急性脑缺氧作用,提示蜕皮甾酮可改善记忆障碍,具有较高的药用价值．     

Protective effect of Cnestis ferruginea and its active constituent on scopolamine-induced memory impairment in mice: A behavioral and biochemical study

Abstract

Context: Cnestis ferruginea Vahl ex DC (Connaraceae) (CF) is used in traditional African medicine in the management of CNS disorders. The degeneration and dysfunction of cholinergic neurons is closely associated with the cognitive deficits of Alzheimer’s disease (AD) and oxidative stress has been implicated in its pathogenesis. However, the influence of C. ferruginea on the cholinergic system and oxidative stress parameters has not been explored.

Objective: The present study investigates the effect of methanol root extract of C. ferruginea and its active constituent amentoflavone (CF-2) on memory, oxidative stress and acetylcholinesterase (AChE) activity in scopolamine-induced amnesia.

Materials and methods: Mice were orally treated with CF (25–200?mg/kg), CF-2 (6.25–25?mg/kg) for three days and memory impairment was induced by intraperitoneal injection of scopolamine (3?mg/kg). Memory function was evaluated by passive avoidance and Morris water maze tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioral studies.

Results: Scopolamine caused memory impairment along with increased AChE activity and oxidative stress in mice brain. Oral administration of CF and CF-2 significantly prevented scopolamine-induced memory impairment, inhibited AChE and enhanced antioxidant enzyme activity in the brain following scopolamine injection as compared to vehicle administration in scopolamine (i.p.)-treated mice that were comparable to the effect of tacrine.

Discussion and conclusion: The study demonstrated that C. ferruginea and its constituent have significant protective effect against scopolamine-induced memory deficits in mice that can be attributed to their antioxidant and antiAChE activity.     

Water-soluble derivative of propolis mitigates scopolamine-induced learning and memory impairment in mice

The water-soluble derivative of propolis (WSDP) was prepared from fresh Chinese propolis. Its major constituents were identified by high performance liquid chromatography (HPLC) analysis. It has been reported that propolis possessed a broad spectrum of biological activities but including few studies on learning and memory by now. Thus, this study was aimed to investigate the effect of WSDP on scopolamine-induced learning and memory impairment in mice. WSDP (50 mg/kg, 100 mg/kg) was given by intragastric administration (i.g.) 40 min prior to the intraperitoneal (i.p.) injection of scopolamine (1 mg/kg).The effect on amnesia was investigated with both hidden-platform acquisition training and probe trial testing in Morris water maze test. The results from 100 mg/kg WSDP group showed significant mitigation scopolamine-induced amnesia in mice. Furthermore, WSDP's effect on the acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus was also assayed. As a result, WSDP (100 mg/kg) significantly inhibited AChE activity in the hippocampus of scopolamine-treated mice. These results indicated that WSDP may mitigate amnesia in vivo through inhibition of AChE activity in the hippocampus, which suggested propolis may have potential as a pharmaceutical of brain protection with elderly population for preventing Alzheimer's disease (AD) and other neurodegenerative diseases.