Effect of styrene on levels of serotonin,noradrenaline, dopamine and activity of acetyl cholinesterase and monoamine oxidase in rat brain

Oral intubation of styrene (1 ml/kg body weight daily) in adult male albino rats for 15 days produced a significant increase in serotonin and nor-adrenaline but no change in dopamine contents in brain. The brain of treated animals also showed a significant decrease in monoamine oxidase (MAO) but no change in acetyl cholinesterase (AChE) activity. The neurotoxic effects of styrene may be mediated through alterations in levels of these biogenic amines in the brain tissue.     

孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制

目的观察孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制。方法东莨菪碱(1mg·kg-1,ip)造成小鼠记忆损伤模型,利用被动逃避实验评价小鼠记忆成绩,并测定给药后24h小鼠皮质和海马胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的活性。结果在被动逃避实验中,东莨菪碱造成小鼠记忆损伤,孕酮(1、10mg·kg-1,sc)预处理能减少跳台错误次数(P<0.05),延长跳台潜伏期(P<0.01)和避暗潜伏期(P<0.01)。东莨菪碱增加皮质和海马AChE活性,降低ChAT活性,孕酮(1mg·kg-1,sc)预处理抑制皮质和海马AChE活性的增加(P<0.01),升高皮质(P<0.05)和海马(P<0.01)ChAT活性。结论孕酮可以改善东莨菪碱所致记忆损伤,机制可能与其抑制皮质和海马AChE活性、升高ChAT活性有关。     

Dose-response effect of black maca (Lepidium meyenii) in mice with memory impairment induced by ethanol

Previous studies have shown that black variety of maca has beneficial effects on learning and memory in experimental animal models. The present study aimed to determine whether the hydroalcoholic extract of black maca (BM) showed a dose-response effect in mice treated with ethanol 20% (EtOH) as a model of memory impairment. Mice were divided in the following groups: control, EtOH, ascorbic acid (AA) and 0.125, 0.25, 0.50 and 1.00?g/kg of BM plus EtOH. All treatments were orally administered for 28 days. Open field test was performed to determine locomotor activity and water Morris maze was done to determine spatial memory. Also, total polyphenol content in the hydroalcoholic extract of BM was determined (0.65?g pyrogallol/100?g). Mice treated with EtOH took more time to find the hidden platform than control during escape acquisition trials; meanwhile, AA and BM reversed the effect of EtOH. In addition, AA and BM ameliorated the deleterious effect of EtOH during the probe trial. Correlation analyses showed that the effect of BM a dose-dependent behavior. Finally, BM improved experimental memory impairment induced by ethanol in a dose-response manner due, in part, to its content of polyphenolic compounds.     

Biochemical characteristics of a potential antidepressant, 2-(7-indenyloxymethyl)morpholine hydrochloride (YM-08054-1)

The effects of potential antidepressant, 2-(7-indenyloxymethyl)morpholine hydrochloride (YM-08054-1), on uptake, release and oxidative deamination of catecholamines and serotonin [5-hydroxytryptamine(5-HT)] were studied in vitro with rat brain, and compared with the effects of several tricyclic antidepressants and viloxazine a structural analogue of YM-08054-1. YM-08054-1 at concentrations of less than 1 μM. considerably inhibited 5-HT uptake by synaptosomes from rat whole brain as well as noradrenaline (NA) uptake by synaptosomes from rat hippocampus, similar to amitriptyline. Viloxazine and iprindole were weak inhibitors in both uptake reactions. In the release of either [¹⁴C] -5-HT from [¹⁴C]-5-HT-prelabeled hypothalamic slices or [¹⁴C]NA from [¹⁴C] NA-prelabeled hippocampal slices, YM-08054-1 and amitriptyline were much less potent than such typical potent releasers as methamphetamine and tyramine. YM-08054-1 was also found to be a weak inhibitor of both type A and type B monoamine oxidases, whereas the tricyclic antidepressants preferentially inhibited the type B enzyme. These biochemical results indicate that YM-08054-1 may be an amitriptyline-like antidepressant, but distinct from viloxazine.     

Maca (Lepidium meyenii) and yacon (Smallanthus sonchifolius) in combination with silymarin as food supplements: in vivo safety assessment.

Yacon and maca are native Andean crops with growing popularity as food supplements often in combination with other components, e.g. silymarin. There are however no published data on their toxicity and safety in humans. The aim of our randomized placebo-controlled 90-day study was to evaluate the effects of yacon and maca in combination with silymarin on plasma and lipoprotein lipids, serum glucose and safety parameters in patients suffering from the metabolic syndrome. No adverse effects were found in volunteers using silymarin (0.8 g/day), silymarin+yacon (0.8+2.4 g/day) and silymarin+maca (0.6+0.2 g/day). A moderate AST level and diastolic blood pressure increase was found in volunteers using maca (0.6 g/day). In conclusion, the combination silymarin+yacon appears to be promising as a nutraceutical in the prevention of diseases with a proatherogenic lipoprotein profile and liver steatosis. The effect of maca on AST level and blood pressure must be considered when using high doses of maca powder. This effect could be reversed by supplementation with silymarin.     

Moclobemide (Ro 11-1163) vs. clomipramine in the treatment of depression: A double-blind multicenter study in Belgium

A multicenter study to compare the antidepressant efficacy and the tolerance of moclobemide (Ro 11-1163) to clomipramine was performed in parallel groups of patients with minor depression. The duration of the study was 6 weeks, with weekly assessments by means of Hamilton Scale of Depression (HRDS) and the Clinical Global Impression (CGI). The efficacy of moclobemide was found to be as good as that of clomipramine. The results for tolerability were possibly in favor of moclobemide. It was recommended that consumption of tyramine-containing foods be kept to a minimum or avoided and no hypertensive crises were reported.     

Donepezil in Alzheimer's disease: an evidence-based review of its impact on clinical and economic outcomes

INTRODUCTION: Donepezil is indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is a specific and reversible inhibitor of acetylcholinesterase (AChE); by increasing levels of available acetylcholine, donepezil may compensate for the loss of functioning cholinergic brain cells. AIMS: This review evaluates the clinical impact of donepezil by assessing randomized controlled and open-label naturalistic trials, as well as observational studies. A broad perspective is gained of its effectiveness on various outcomes. EVIDENCE REVIEW: There is strong evidence that donepezil has efficacy against the three major domains of Alzheimer's disease symptoms, namely functional ability, behavior, and cognition. The strongest evidence is for improvement or less deterioration in global outcomes and cognition in the short to medium term. There is limited evidence that improved global outcomes are maintained in the long term and clear evidence to support long-term maintenance of cognitive benefits. Also, donepezil appears to maintain function in the long term and there is some level 1 and 2 evidence of improved or limited deterioration in behavior or mood in the short to medium term. Despite donepezil's effects on major symptoms of Alzheimer's disease, its impact on patients' quality of life has not been consistently demonstrated, perhaps reflecting the difficulty of assessing this aspect in this patient population. Donepezil may also lessen caregiver burden. Donepezil has some effect on markers of brain function, but more data are needed to confirm a neuroprotective effect. There is limited and conflicting evidence that long-term donepezil treatment delays time to institutionalization. There is some evidence that donepezil may be cost effective, especially when unpaid caregiver costs are considered. Donepezil is generally safe and well tolerated. CLINICAL VALUE: AChE inhibitors are the only agents recommended for the treatment of cognitive decline in patients with mild to moderate Alzheimer's disease. Donepezil is more effective than placebo and is well tolerated in improving the major symptoms of this disease. Improvements are usually modest, although stabilization of cognitive and functional symptoms with donepezil can also be considered an important clinical outcome. Donepezil may lessen caregiver burden. Donepezil may also be cost effective, especially when unpaid caregiver costs are considered. More data are required from randomized controlled trials with long-term follow-up to confirm its cost effectiveness and impact on quality of life, disease progression, and time to institutionalization.     

Efficacy study of Prunus amygdalus (almond) nuts in scopolamine-induced amnesia in rats

Objective:

Cognitive disorders such as amnesia, attention deficit and Alzheimer’s disease are emerging nightmares in the field of medicine because no exact cure exists for them, as existing nootropic agents (piractam, tacrine, metrifonate) have several limitations. The present study was undertaken to investigate the effect of Prunus amygdalus (PA) nuts on cognitive functions, total cholesterol levels and cholinesterase (ChE) activity in scopolamine-induced amnesia in rats.

Materials and Methods:

The paste of PA nuts was administered orally at three doses (150, 300 and 600 mg/kg) for 7 and 14 consecutive days to the respective groups of rats. Piracetam (200 mg/kg) was used as a standard nootropic agent. Learning and memory parameters were evaluated using elevated plus maze (EPM), passive avoidance and motor activity paradigms. Brain ChE activity and serum biochemical parameters like total cholesterol, total triglycerides and glucose were evaluated.

Results:

It was observed that PA at the above-mentioned doses after 7 and 14 days of administration in the respective groups significantly reversed scopolamine (1 mg/kg i.p.)-induced amnesia, as evidenced by a decrease in the transfer latency in the EPM task and step-down latency in the passive avoidance task. PA reduced the brain ChE activity in rats. PA also exhibited a remarkable cholesterol and triglyceride lowering property and slight increase in glucose levels in the present study.

Conclusion:

Because diminished cholinergic transmission and increase in cholesterol levels appear to be responsible for the development of amyloid plaques and dementia in Alzheimer patients, PA may prove to be a useful memory-restorative agent. It would be worthwhile to explore the potential of this plant in the management of Alzheimer’s disease.     

The ameliorating effect of the extract of the flower of Prunella vulgaris var.lilacina on drug-induced memory impairments in mice

Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and its flowers are used to treat inflammation in traditional Chinese medicine. In the present study, we studied the effects of the ethanolic extract of the flower of P. vulgaris var. lilacina (EEPV) on drug-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. EEPV (25 or 50 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (P < 0.05). In the Morris water maze task, EEPV (25 mg/kg, p.o.) significantly shortened escape latencies in training-trials. Furthermore, swimming times within the target zone during the probe-trial were significantly increased as compared with scopolamine-treated mice (P < 0.05). In addition, the reduced latency induced by MK-801 treatment in the passive avoidance task was ameliorated by EEPV (25 mg/kg, p.o.) (P < 0.05). Additionally, the ameliorating effect of EEPV on scopolamine-induced memory dysfunction was antagonized by a sub-effective dose of MK-801. These results suggest that EEPV would be useful for treating cognitive impairments induced by cholinergic dysfunction, and that it exerts its effects via NMDA receptor signaling.     

Ranuncoside’s attenuation of scopolamine-induced memory impairment in mice via Nrf2 and NF-ĸB signaling

Scopolamine is a well-known pharmacological agent responsible for causing memory impairment in animals, as well as oxidative stress and neuroinflammation inducer which lead to the development of Alzheimer disease. Although a cure for Alzheimer’s disease is unavailable. Ranuncoside, a metabolite obtained from a medicinal plant has demonstrated antioxidant and anti-inflammatory properties in vitro, making it a promising treatment with potential anti-Alzheimer disease properties. However, as ranuncoside has not been evaluated for its antioxidant and anti-neuroinflammatory properties in any in vivo model, our study aimed to evaluate its neurotherapeutic efficacy against scopolamine-induced memory impairment in adult male albino mice.Mice were randomly divided into four experimental groups. Mice of group I was injected with saline, group II was injected with scopolamine (1 mg/kg/day) for 3 weeks. After receiving a daily injection of scopolamine for 1 week, the mice of group III were injected with ranuncoside (10 mg/kg) every other day for 2 weeks along with scopolamine daily and group IV were injected with ranuncoside on 5th alternate days. Behavioral tests (i.e., Morris water maze and Y-maze) were performed to determine the memory-enhancing effect of ranuncoside against scopolamine's memory deleterious effect. Western blot analysis was also performed to further elucidate the anti-neuroinflammatory and antioxidant effects of ranuncoside against scopolamine-induced neuroinflammation and oxidative stress.Our results showed memory-enhancing, anti-neuroinflammatory effect, and antioxidant effects of ranuncoside against scopolamine by increasing the expression of the endogenous antioxidant system (i.e., Nrf2 and HO-1), followed by blocking neuroinflammatory markers such as NF-κB, COX-2, and TNF-α. The results also revealed that ranuncoside possesses hypoglycemic and hypolipidemic effects against scopolamine-induced hyperglycemia and hyperlipidemia in mice as well as scopolamine’s hyperglycemic effect. In conclusion, our findings suggest that ranuncoside could be a potential agent for the management of Alzheimer’s disease, hyperglycemia, and hyperlipidemia.     

Novel bis-(-)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC₅₀ values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC₅₀ values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD.     

Design,synthesis, biological evaluation,and docking study of 4‐isochromanone hybrids bearing N‐benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II)

A series of novel 4‐isochromanone compounds bearing N‐benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti‐AChE activity with an IC₅₀ value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti‐Alzheimer's disease agents.     

Production and on-line acetylcholinesterase bioactivity profiling of chemical and biological degradation products of tacrine

The present paper describes a methodology for rapid assessment of chemical and biological degradation products of tacrine and their bioactivity for acetylcholinesterase (AChE). Analysis was achieved by utilizing liquid chromatography coupled to parallel high resolution mass spectrometry and an on-line continuous-flow AChE bioassay for biochemical detection. Key advantage of the strategy described involves the straightforward chemical production of large quantities of products of which many were the same as formed during the biological degradation by cytochromes P450 (CYPs). For this, chemical degradation of tacrine was evaluated under acidic, basic and oxidative conditions as well as elevated temperatures and light exposure. Chemical degradation products were only formed after 2 h under reflux with 3% hydrogen peroxide, where more than 50% of tacrine was converted to degradation products. Many of these products showed bioactivity. Mostly, mono-, di- or tri-oxygenated compounds were observed. This study demonstrated that the combination of chemical and biological degradation provides valuable information indicating that assessment of biological activity is important not only for biological degradation products, but also for chemical degradation products when formed. Furthermore, chemical degradation can be used to produce conveniently and in relatively large quantities clean mixtures of compounds that are also produced during metabolic incubations.     

Crocus Sativus L. (Saffron) in Alzheimer’s Disease Treatment: Bioactive Effects on Cognitive Impairment

Crocus sativus L. (saffron) appears to own neuroprotective effects on cognitive impairment in patients with Alzheimer’s disease (AD). The purpose of this work is to review evidence and mechanisms of saffron-induced therapeutic outcomes and measureable cognitive benefits in AD.The literature was reviewed, and preclinical and clinical studies were identified. In vitro and in vivo preclinical studies were selected according to these criteria: 1) development of saffron pharmacological profile on biological or biophysical endpoints; 2) evaluation of saffron efficacy using animal screens as an AD model, and 3) duration of the studies of at least 3 months. As for the clinical studies, the selection criteria included: 1) patients aged ≥ 60, 2) AD diagnosis according to National Institute on Aging-Alzheimer''s Association (NIAAA) criteria, and 3) appropriate procedures to assess cognitive, functional, and clinical status. A total of 1477 studies published until November 2020 were identified during an initial phase, of which 24 met the inclusion criteria and were selected for this review.Seventeen in vitro and in vivo preclinical studies have described the efficacy of saffron on cognitive impairment in animal models of AD, highlighting that crocin appears to be able to regulate glutamate levels, reduce oxidative stress, and modulate Aβ and tau protein aggregation. Only four clinical studies have indicated that the effects of saffron on cognitive impairment were not different from those produced by donepezil and memantine and that it had a better safety profile.Saffron and its compounds should be further investigated in order to consider them a safer alternative in AD treatment.     

Effects of carbachol on lead-induced impairment of the long-term potentiation/depotentiation in rat dentate gyrus in vivo.

The present study aims at evaluating the impairment of LTP and depotentiation (DP) of LTP induced by acute lead exposure, and the effects of peripheral carbachol (CCh) application on LTP/DP of acute and chronic lead-exposed rats in dentate gyrus in vivo. Rats (80-100 days) were acutely exposed to lead by intraperitoneal injection of 0.2% lead acetate (PbAc) solution (1.5mg/100g) and/or CCh (1 micro g/100g). Rats were chronically exposed to lead from parturition through adulthood (80-100 days) by the drinking of 0.2% PbAc solution and/or CCh (1 micro g/100g) chronic intraperitoneal injection one week. The input-output (I/O) function, paired-pulse reaction (PPR), excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in response to stimulation applied to the lateral perforant path. Results showed that: first, acute lead exposure significantly depressed the amplitudes of LTP/DP of both EPSP slope and PS amplitude. Second, CCh significantly increased the amplitudes of both EPSP LTP/DP and PS LTP of acute Pb-exposed rats. After CCh treatment, the magnitudes of EPSP LTP/DP and PS LTP of acute Pb-exposed rats showed no significant difference with controls. Third, Chronic CCh application also reversed chronic Pb-induced impairment of PS LTP and EPSP DP of LTP. As CCh does not cross blood-brain barrier in healthy animals, the data suggest that CCh may traverse BBB in Pb-exposed animals and cure Pb-induced dysfunction of learning and memory.     

Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders

Histone acetylation/deacetylation is a master regulation of gene expression. Among the enzymes involved in this process, the CREB-binding protein (CBP) displays important functions during central nervous system development. Increasing evidence shows that CBP function is altered during neurodegenerative processes. CBP loss of function has now been reported in several diseases characterized by neurological disorders such as the Rubinstein-Taybi syndrome or polyglutamine-related pathologies (Huntington's disease). Our recent work suggests that CBP loss of function could also be involved in Alzheimer's disease and amyotrophic lateral sclerosis. In a simplified apoptotic model of primary neurons, we described CBP as a substrate of apoptotic caspases, an alternative to its classical proteasomal degradation. In these neuronal death contexts, histone acetylation levels were decreased as well. Altogether, these data point to a central role of CBP loss of function during neurodegeneration. In order to restore proper acetylation levels, a proposed therapeutic strategy relies on HDAC inhibition. Nevertheless, this approach lacks of specificity. Therefore new drugs targeted at counteracting CBP loss of function could stand as a valid therapeutic approach in neurodegenerative disorders. The challenge will be to respect the fine-tuning between cellular HAT/HDAC activities.     

Reversible inhibition of acetylcholinesterase by eseroline,an opioid agonist structurally related to physostigmine (eserine) and morphine

The action of eseroline—(3aS, 8aR)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b] indol-5-ol—salicylate was tested on preparations of ChE from different sources and on the longitudinal muscle of guinea-pig ileum. While eseroline is extremely weak-acting on horse serum BuChE (K_i = 208 ± 42 μM), it is a rather strong competitive inhibitor of AChE's, its K_i being 0.15 ± 0.08 μM, 0.22 ± 0.10 μM and 0.61 ± 0.12 μM in electric eel, human RBC and rat brain, respectively. Eseroline inhibitory action on AChE is independent of the duration of pre-incubation and appears fully developed in less than 15 sec. This action is also rapidly reversible; after pre-incubation followed by dilution, maximum enzymic activity is regained within 15 sec. The electrically-evoked contractions of the longitudinal strip were inhibited by concentrations of eseroline in the range 0.2–15 μM, while they were increased by concentrations over 20 μM. In the same preparation, without electrical stimulation, but in the presence of naloxone, eseroline induced contractions at concentrations higher than 5 μM. This effect was antagonized by atropine. The inhibitory activity of eseroline parallels, as regards selectivity, potency and kinetics, that of the phenolic anticurare agent edrophonium, while it differs markedly from that of physostigmine.     

Antioxidants significantly affect the formation of different classes of isoprostanes and neuroprostanes in rat cerebral synaptosomes

Lipid peroxidation has been implicated in the pathogenesis of a number of diseases, including neurodegenerative disorders. Evidence that antioxidants can affect the clinical course of neurodegenerative diseases is limited. In the present study, we examined the ability of five common antioxidants or antioxidant combinations, alpha-tocopherol, gamma-tocopherol, ascorbic acid, GSH ethyl ester, and a combination of ascorbate and alpha-tocopherol, to modulate lipid peroxidation in peroxidizing rat cerebral synaptosomes, a well-characterized model of oxidant injury. In these studies, we quantified isoprostanes (IsoPs) derived from arachidonic acid as an index of whole tissue oxidation and neuroprostanes (NeuroPs) formed from docosahexaenoic acid as a marker of selective neuronal peroxidation. We report that these various antioxidants displayed markedly different capacities to inhibit IsoP and NeuroP formation with the most potent effects on IsoPs observed for ascorbate, GSH ethyl ester, and the alpha-tocopherol-ascorbate combination. alpha-Tocopherol was slightly less potent and gamma-tocopherol significantly less effective. The concentration-response relationships were significantly different for NeuroP formation with the antioxidants being significantly less potent than for IsoP generation. In particular, alpha-tocopherol did not inhibit NeuroP formation at concentrations up to 100 microM. We also determined that tocopherols, in particular alpha-tocopherol, act in vitro as reducing agents to convert IsoP and NeuroP endoperoxides to reduced F-ring compounds, a finding we have observed previously in vivo in brain. These studies are of importance because they have further defined the role of antioxidants to modulate the formation of lipid peroxidation products in peroxidizing brain tissue. In addition, they suggest that alpha-tocopherol may not be a particularly effective agent to inhibit oxidant stress in the terminal compartment of neurons in the central nervous system.     

N-(2-Cyanoethyl)tranylcypromine,a Potential Prodrug of Tranylcypromine: Its Disposition and Interaction with Catecholamine Neurotransmitters in Brain

The disposition of the N-cyanoethyl analogue of tranylcypromine (TCP) and the TCP formed from it have been studied in the rat brain following intraperitoneal (ip) administration (0.1 mmol/kg) and the resultant data compared with those obtained following an equimolar dose of TCP. Brain concentrations of the neurotransmitter amines dopamine (DA) and noradrenaline (NA) have also been determined, as well as the percentage inhibition of monoamine oxidase (MAO) types A and B. Our results indicate that the N-cyanoethyl analogue may be a useful prodrug of TCP, providing lower but more sustained concentrations of TCP in brain. Brain levels of DA were increased in a similar pattern after CE-TCP or TCP. Brain levels of NA were decreased by TCP at most time intervals, while CE-TCP produced a much less pronounced effect. Both CE-TCP and TCP inhibited MAO-A and MAO-B, with maximum inhibition occurring 60 min after CE-TCP dosing and 30 min after dosing with TCP, times at which brain concentrations of CE-TCP and TCP were at the maximum.     

Effects of Xanthoceraside on learning and memory impairment in mice induced by i.c.v.Aβ_(1-42)

Objective To investigate the improvement of Xanthoceraside on learning and memory impairment in mice induced by intracerebroventricular injection of Aβ1-42(i.c.v.Aβ1-42)and the possible mechanisms of its protection against AD.Methods Y-maze test,water-maze test and step-down test were used to investigate the learning and memory ability of mice;Biochemical analysis was used to detect the activity of CAT,T-AOC,ATPase and the content of MDA.Results The results showed that Xanthoceraside could significantly increase the alternation behavior in Y-maze test,shorten swimming time in water maze test and increase the latency and decrease the number of errors and the total time of shock in step-down test.Xanthoceraside markedly increased the activity of CAT,T-AOC,ATPase,at the same time,decreased the content of MDA.Conclusions Xanthoceraside can improve learning and memory impairment in mice induced by i.c.v.Aβ1-42 significantly.The mechanism may be associated with the protection against damage induced by free radicals;the inhibition of membrane lipid peroxidation and the improvement of metabolism of brain.