Amnesia In Mice Research Articles

Genistein Ameliorates Scopolamine-Induced Amnesia in Mice Through the Regulation of the Cholinergic Neurotransmission, Antioxidant System and the ERK/CREB/BDNF Signaling.

Genistein (GE) was reported to exert a wide spectrum of biological activities, including antioxidant, anti-inflammatory, anti-mutagenic, anticancer, and cardio-protective effects. In addition, both clinical and preclinical studies have recently suggested GE a potential neuroprotective and memory-enhancing drug against neurodegenerative diseases. The animal model of scopolamine (Scop)-induced amnesia is widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases. However, there is no report about the effects of GE on Scop-induced amnesia in mice. Therefore, the present study was carried out to investigate the beneficial effects and potential mechanism of GE against Scop-induced deficits in mice. The mice were orally pretreated with either GE (10, 20, and 40 mg/kg) or donepezil (1.60 mg/kg) for 14 days. After the pretreatment, the open field test was conducted to assess the effect of GE on the locomotor activity of mice. Thereafter, mice were daily injected with Scop (0.75 mg/kg) intraperitoneally to induce memory deficits and subjected to the cognitive behavioral tests including the Object Location Recognition (OLR) experiment and Morris Water Maze (MWM) task. After the behavioral tests, biochemical parameter assay and western blot analysis were used to examine the underlying mechanisms of its action. The results showed that GE administration significantly improved the cognitive performance of Scop-treated mice in OLR and Morris water maze tests, exerting the memory-enhancing effects. Additionally, GE remarkably promoted the cholinergic neurotransmission and protected against the oxidative stress damage in the hippocampus of Scop-treated mice, as indicated by decreasing AChE activity, elevating ChAT activity and Ach level, increasing SOD activity, lowering the level of MDA and increasing GSH content. Furthermore, GE was found to significantly upregulate the expression levels of p-ERK, p-CREB and BDNF proteins in the hippocampus of Scop-treated mice. Taken together, these results for the first time found that GE exerts cognitive-improving effects in Scop-induced amnesia and suggested it may be a potential candidate compound for the treatment of some neurodegenerative diseases such as Alzheimer’s Disease (AD).

Lemon Grass Tea Enhanced Memory Function and Attenuated Scopolamine-Induced Amnesia in Mice Via Inhibition of Oxidative Stress and Acetyl-Cholinesterase Activity

ABSTRACTThe aqueous leaf extract of Cymbopogon citratus (CYC) was evaluated for memory functions on scopolamine (SCO)-induced amnesia in mice. Male mice received CYC (25, 50, or 100 mg kg−1) or saline (10 mL kg−1) orally for 7 consecutive days. In the interaction studies, the mice were given CYC (25, 50, or 100 mg kg−1, p.o) 30 min before SCO (3 mg kg−1, i.p) for 7 consecutive days. Thirty minutes after the last treatment in each case, memory function was evaluated using Y-maze and object recognition tests. The biomarkers of oxidative stress (malondialdehyde and glutathione) and acetyl-cholinesterase activity in the brain of SCO-treated mice were also determined. CYC increased memory performance and attenuated SCO-induced amnesia in mice. The extract also attenuated increased oxidative stress and acetyl-cholinesterase activity induced by SCO. Findings of this study suggested the potential use of the aqueous leaf extract of C. citratus as a phytotherapeutic agent for memory decline.

Evaluation of learning and memory effect of atorvastatin and simvastatin in alprazolam induced amnesia in mice

Background: The study was undertaken to evaluate the learning and memory effect of lipid lowering drugs atorvastatin and simvastatin in alprazolam induced amnesic mice.Methods: The study was carried out on albino mice, divided into 4 groups of 6 animals each (either sex, 3-4 months of age, weight 25-30g). Amnesia was induced by administering Alprazolam (2mg/kg for 14 days) in all 4 groups from 1st to 14th day. In addition, group 2, 3 and 4 received Piracetam (400mg/kg), Atorvastatin (5mg/kg) and Simvastatin (5mg/kg) from 8th to 14th day respectively. The learning and memory of the animals was assessed by employing Elevated plus maze (EPM) and Step-down type passive avoidance (SDA) model.Results: Results were compared among the different groups using one way-ANOVA followed by post hoc Tukey’s test. The measured parameters were compared with standard drug Piracetam. In EPM model Atorvastatin (p<0.049) and Simvastatin (p<0.007) were comparable with standard drug Piracetam, whereas in SDA model only simvastatin group (p<0.001) showed significant result.Conclusions: In EPM model, both the statins showed significant improvement in learning and memory in alprazolam induced amnesic mice. However further studies are required to support these observations.

In Vitro Anti-cholinesterase and Cognitive Enhancing Properties of Essential Oils from Piper nigrum L. and Monodora myristica (Gaertn) Dunal

Aging in humans generally is associated with deterioration of cognitive abilities, particularly of learning and memory leading to dementia, including Alzheimer’s disease. A number of herbal medicines are reported to improve brain function and intelligence. In the present study, the ameliorating effects of essential oil extracted from Piper nigrum and Monodora myristica on learning and memory in Scopolamine induced amnesic mice were determined using two cognitive behavioural paradigms: the Step-Through Passive Avoidance and Morris-Water Maze test. Essential oils were obtained by hydro-distillation using a Clavenger-type apparatus and their profiles analyzed by GC-MS. Inhibitory effects on AChE and BuChE were investigated by Ellman’s method. The animals were assessed for performance by measuring the Step-Through Latency Time (SLT) and Escape Latency Time (ELT). Brain cholinesterase activities were assayed in brain tissues from the mice. The results showed that M. myristica and P. nigrum oils were characterized by 51 (94.76%) and 61 (90.65%) components, respectively. M. myristica is dominated by α-phellandrene (18.13%), while P. nigrum is dominated by β-pinene (5.92%) and caryophyllene (4.55%). Both oils at 416 µg/ml elicited significant inhibitory (p>0.05) activity with M. myristica exhibiting a stronger inhibition against AChE and BuChE than P. nigrum. This trend was also exhibited significantly (p>0.05) in both ELT and the SLT when compared to scopolamine-treated group. In conclusion, the seeds of M. myristica and P. nigrum are potential sources of active metabolites with anti-cholinesterase and cognition enhancing properties, but M. myristica exhibited a higher activity. Â

Novel lactopeptides in fermented dairy products improve memory function and cognitive decline.

Alongside the rapid growth in aging populations, prevention of age-related memory decline and dementia has become a high priority. Several epidemiological and clinical studies have concluded that fermented dairy products can help to prevent cognitive decline; furthermore, intake of Camembert cheese prevents Alzheimer's pathology in model mice. To elucidate molecular mechanisms underlying the preventive effects of fermented dairy products, here we screened peptides from digested fermented dairy products for ability to improve memory function in a scopolamine-induced amnesia mouse model. We found that Trp-Tyr (WY)-containing peptides from whey protein improved memory function in the mice, and the effects were confirmed in aged mice. The WY-containing peptides directly inhibited monoamine oxidase-B activity and increased dopamine levels in brain tissue. Pretreatment with dopamine receptor antagonist abolished the improvement in memory function due to WY-containing peptides. These results suggest that WY-containing peptides in fermented dairy products increase monoamine levels by inhibiting monoamine oxidase-B activity, helping to prevent age-related cognitive decline.

The phosphodiesterase 5 inhibitor, KJH‐1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage

Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine-induced cognitive dysfunction, using memory-related behavioural tests and biochemical assays. In mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively. KJH-1002, a novel and potent inhibitor of PDE5 (IC50 0.059±0.04nmol·L-1 ), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased cGMP levels in the cortex and the scopolamine-reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain-derived neurotrophic factor in the cortex and hippocampus were restored by KJH-1002 treatment. In addition, KJH-1002 administration increased the activities of SOD, glutathione peroxidase and glutathione reductase, and decreased the level of malondialdehyde. KJH-1002 restored cognitive function in scopolamine-induced amnesia mice by activating the cGMP/CREB signalling pathway and attenuating oxidative stress. The beneficial effects of KJH-1002 on cognition indicate its potential as a therapeutic candidate for Alzheimer's disease.

PHARMACOLOGICAL EVIDENCE FOR THE ANTIAMNESTIC EFFECTS OF ROOTS OF DESMODIUM TRIQUETRUM DC IN MICE

Desmodium triquetrum DC. (Leguminosae) is widely used in Ayurveda for treating various neurological disorders. In the present study, the effectiveness of aqueous extract of roots of D. triquetrum in mice in attenuating scopolamine-induced amnesia was investigated. Passive avoidance paradigm was used to assess long-term memory. In order to delineate the possible mechanism through which D. triquetrum elicits the anti-amnesic effects, we studied its influence on central cholinergic activity by estimating the acetylcholine content of the whole brain and acetylcholinesterase activity at different regions of the mouse brain, viz., cerebral cortex, midbrain, medulla oblongata and cerebellum. Pretreatment with D. triquetrum (50, 100 and 200 mg/kg, p.o.) for seven successive days, reversed scopolamine induced amnesia in mice. D. triquetrum increased mice brain acetylcholine content and decreased acetyl cholinesterase activity in a similar fashion to the standard cerebro-protective drug piracetam. The aqueous extract of roots D. triquetrum can be used to delay the onset and reducing the severity of the symptoms of dementia and Alzheimer's disease.

Neuroprotective Effects of Soy Isoflavones on Scopolamine-Induced Amnesia in Mice.

In the recent years, interest in soybean as a neuroprotective nutrient in the management of Alzheimer’s disease (AD) has increased and soy isoflavones (SI), as kinds of soybean phytochemicals, are thought to be biologically active components that confer this beneficial effect against neurodegenerative diseases. However, the neuroprotective effect of SI is not well understood. Therefore, the present study (30 days) was conducted to investigate the neuroprotective effects of soy isoflavones (SI) on scopolamine (SCOP)-induced memory impairments in Institute of Cancer Research (ICR) mice (aged 4 weeks) and to elucidate its underlying mechanisms of action. SI (40 mg/kg) administration improved the cognitive performance of SCOP-treated mice in an object location recognition task and the Morris water maze test. SI (40 mg/kg) administration significantly enhanced cholinergic system function and suppressed oxidative stress levels in the hippocampus of SCOP-treated mice. Furthermore, SI (40 mg/kg) treatment markedly upregulated the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression levels in the hippocampus. Taken together, these results demonstrated that soy isoflavones exerted a significant neuroprotective effect on cognitive dysfunctions induced by scopolamine, suggesting that soy isoflavones could be a good candidate for possible treatment of neurodegenerative diseases, such as Alzheimer’s disease (AD).

Vdac1 Downregulation Causes Mitochondrial Disintegration Leading to Hippocampal Neurodegeneration in Scopolamine-Induced Amnesic Mice.

Our previous report on hippocampal proteome analysis suggested the involvement of voltage-dependent anion channel (Vdac) 1 in scopolamine-induced amnesia. Further silencing of Vdac1 in young mice reduced the recognition memory. Vdac1 is a porin protein present abundantly on outer mitochondrial membrane. It acts as a transporter of energy metabolites ATP/ADP and Ca2+ ions and helps in communication between mitochondrial matrix and cytosol. As Vdac1-associated energy metabolism may be affected during amnesia, we determined the downstream function of Vdac1 in the present study. The expression of Vdac1 and total ATP level was decreased in the hippocampus of scopolamine-induced amnesic mice. Also, the mitochondrial membrane potential, cristae organization, and morphology were disrupted leading to increased ROS generation and reduced SOD and catalase activity. On the other hand, there was increase in the expression of pro-apoptotic marker proteins (Bax, Bad, Casp 3), leading to rising degenerated neuronal cells in the dentate gyrus and Cornu ammonis 3 and 1 subregions of the hippocampus during amnesia. Further, to check whether Vdac1 downregulation is associated with neurodegeneration, we infused Vdac1 siRNA stereotaxically in the hippocampus of normal young mice. As compared to control, Vdac1 silencing decreased ATP level and mitochondrial membrane potential leading to increase in the number of degenerated neuronal cells in subregions of the hippocampus. Taken together, our study shows that downregulation of Vdac1 causes neurodegeneration through mitochondrial disintegration in the hippocampus of scopolamine-induced amnesic mice.

Neuroprotective Activity of Sesbania grandifolara Seeds Extract Against Celecoxib Induced Amnesia in Mice

Neuroprotective Activity of Sesbania grandifolara Seeds Extract Against Celecoxib Induced Amnesia in Mice

Antioxidant, anticholinesterase and antifatigue effects of Trichilia catigua (catuaba)

BackgroundTrichilia catigua A. Juss. (Meliaceae) is a species known as catuaba and used in folk medicine for the treatment of fatigue, stress, impotence and memory deficit. The main phytochemical compounds identified in the barks of T. catigua are flavalignans, flavan-3-ols and flavonoids which are associated with its antioxidant activity. Pre-clinical studies with T. catigua extracts have identified many pharmacological properties, such as anti-inflammatory, antidepressant, antinociceptive, pro-memory and neuroprotective against ischemia and oxidative stress. This study was designed in order to compare the chemical composition and in vitro antioxidant and anticholinesterase activity of four different polarity extracts and selected the one most active for in vivo studies in rodent models of stress, fatigue and memory.MethodsHexane, chloroform, hydroalcoholic and aqueous extracts from bark of Trichilia catigua were analyzed by RPHPLC-DAD-ESI-MS/MS. Antioxidant activity was assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay and acetylcholinesterase inhibition by Ellman’s modified method. In vivo studies (stress, fatigue and memory) were carried out with adult male mice and rats treated with hydroalcoholic extract in doses of 25–300 mg/kg (p.o.).ResultsWe confirmed the presence of cinchonain IIa, Ia and Ib, as main constituents in the four extracts, while procyanidins were detected only in hydroalcoholic extract. Antioxidant and anticholinesterase activity were observed for all extracts, with most potent activity found on the hydroalcoholic extract (EC50 = 43 μg/mL and IC50 = 142 μg/mL for DPPH scavenger and acetylcholinesterase inhibition, respectively). The treatment of laboratory animals with hydroalcoholic extract did not protect rats from cold immobilization stress and did not prevent the scopolamine-induced amnesia in mice. However, the treatment of mice with the hydroalcoholic extract partially reduced the fatigue induced by treadmill, since the highest dose increased the spontaneous locomotor activity and reduced the deficit on grip strength after the forced exercise (p < 0.05), in some observation times.ConclusionsThese data suggest the hydroalcoholic extract as the most suitable for plant extraction and partially support the folk use of T. catigua as antifatigue drug.Graphical abstract.Trichilia catigua hydroalcoholic extract exhibits antioxidant and anticholinesterase activity in vitro and reduces the fatigue induced by forced exercise.

Ameliorative potential of desalted Salicornia europaea L. extract in multifaceted Alzheimer\u2019s-like scopolamine-induced amnesic mice model

The Salicornia europaea L. (SE) plant is a halophyte that has been widely consumed as a seasoned vegetable, and it has been recently reported to counteract chronic diseases related to oxidative and inflammatory stress. In this study, we performed an initial phytochemical analysis with in vitro biochemical tests and chromatographic profiling of desalted and enzyme-digested SE ethanol extract (SE-EE). Subsequently, we evaluated the anti-neuroinflammatory and ameliorative potential of SE-EE in LPS-inflicted BV-2 microglial cells and scopolamine-induced amnesic C57/BL6N mice, respectively. SE-EE possess considerable polyphenols and flavonoids that are supposedly responsible to improve its bio-efficacy. SE-EE dose-dependently attenuated LPS-induced inflammation in BV-2 cells, significantly repressed behavioural/cognitive impairment, dose-dependently regulated the cholinergic function, suppressed oxidative stress markers, regulated inflammatory cytokines/associated proteins expression and effectively ameliorated p-CREB/BDNF levels, neurogenesis (DCX stain), neuron proliferation (Ki67 stain) in scopolamine-administered mice. Thus, SE-EE extract shows promising multifactorial disease modifying activities and can be further developed as an effective functional food, drug candidate, or supplemental therapy to treat neuroinflammatory mediated disorders.

Antiamnesic and Neuroprotective Effects of Leaves of Mimusops elengi on Brain Aging and Chemically Induced Amnesia in Mice

Antiamnesic and Neuroprotective Effects of Leaves of Mimusops elengi on Brain Aging and Chemically Induced Amnesia in Mice

Synergistic Effect of the Combination of Ethanolic Extract of Piper cubeba and Polyherbal Formulation Triphala on Learning and Memory Enhancement against Scopolamine Induced Amnesia in Mice

Alzheimer’s disease is the fourth most common cause of death which estimated that, by 2030 more than 65 million people of world will be living with dementia. Cognition enhancers attenuate some aspects of brain dysfunction by acting on cholinergic system but having limited use. About 75-80% of world population still mainstay on use of traditional medicine. In the present study, ethanolic extract of Piper cubeba L. (Piperaceae) and its combination with Ayurvedic preparation triphala was evaluated for learning and memory enhancement activity against scopolamine induced amnesia. The passive avoidance behavioral model showed significant (P&lt;0.001) decrease in step down latency for scopolamine injected group whereas extract treated group significantly (P&lt;0.01) apposed the action of scopolamine. However, combination of extract and triphala exhibited more significant (P&lt;0.001) action. Similarly, in Y-maze task, there was significant (P&lt;0.001) increase in percentage same arm returns, decreased alternate arm returns and spontaneous alternations in scopolamine treated group, indicating memory impairment and these changes were significantly (P&lt;0.001) reversed in extract as well as its combination with triphala treated group, suggesting improvement in learning and short term memory function. The extract also exhibited significant reduction in total cholesterol level against Triton-WR 1339 induced acute hypercholesterolemia which represents inhibition of deposition of cellular Aβ- protein and thus reduces the risk of Alzheimer’s disease. Thus, it concludes that, combination of ethanolic extract of Piper cubeba and triphala exhibited synergistic effect on improvement of learning and memory function by modulating cholinergic function in hippocampus region of brain.

Transcriptional co-repressor SIN3A silencing rescues decline in memory consolidation during scopolamine-induced amnesia.

Epigenetic modifications through methylation of DNA and acetylation of histones modulate neuronal gene expression and regulate long-term memory. Earlier we demonstrated that scopolamine-induced decrease in memory consolidation is correlated with enhanced expression of hippocampal DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in mice. DNMT1 and HDAC2 act together by recruiting a co-repressor complex and deacetylating the chromatin. The catalytic activity of HDACs is mainly dependent on its incorporation into multiprotein co-repressor complexes, among which SIN3A-HDAC2 co-repressor is widely studied to regulate synaptic plasticity. However, the involvement of co-repressor complex in regulating memory loss or amnesia is unexplored. This study examines the role of co-repressor SIN3A in scopolamine-induced amnesia through epigenetic changes in the hippocampus. Scopolamine treatment remarkably enhanced hippocampal SIN3A expression in mice. To prevent such increase in SIN3A expression, we used hippocampal infusion of SIN3A-siRNA and assessed the effect of SIN3A silencing on scopolamine-induced amnesia. Silencing of SIN3A in amnesic mice reduced the binding of HDAC2 at neuronal immediate early genes (IEGs) promoter, but did not change the expression of HDAC2. Furthermore, it increased acetylation of H3K9 and H3K14 at neuronal IEGs (Arc, Egr1, Homer1 and Narp) promoter, prevented scopolamine-induced down-regulation of IEGs and improved consolidation of memory during novel object recognition task. These findings together suggest that SIN3A has a critical role in regulation of synaptic plasticity and might act as a potential therapeutic target to rescue memory decline during amnesia and other neuropsychiatric pathologies.

Ebselen inhibits the activity of acetylcholinesterase globular isoform G4 in vitro and attenuates scopolamine-induced amnesia in mice.

There is a well-known relationship between the cholinergic system and learning, memory, and other common cognitive processes. The process for researching and developing new drugs has lead researchers to repurpose older ones. This study investigated the effects of ebselen on the activity of acethylcholinesterase (AChE) isoforms in vitro and in an amnesia model induced by scopolamine in Swiss mice. In vitro, ebselen at concentrations equal or higher than 10 μM inhibited the activity of cortical and hippocampal G4/AChE, but not G1/AChE isoform. Treatment of mice with ebselen (50 mg/kg, i.p.) was effective against impairment of spatial recognition memory in both Y-maze and novel object recognition tests induced by scopolamine (1 mg/kg, i.p.). Ebselen (50 mg/kg) inhibited hippocampal AChE activity in mice. The present study demonstrates that ebselen inhibited the G4/AChE isoform in vitro and elicited an anti-amnesic effect in a mouse model induced by scopolamine. These findings reveal ebselen as a potential compound in terms of opening up valid therapeutic avenues for the treatment of memory impairment diseases.

Effect of Rosuvastatin on learning and memory in scopolamine induced amnesia in Mice

Effect of Rosuvastatin on learning and memory in scopolamine induced amnesia in Mice

Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA-PCL-OH boost delivery of bacosides to the brain.

In the present study, engineered lactoferrin (Lf)-conjugated pH and redox-sensitive polymersomes derived from the triblock copolymer polyethylene glycol-S-S-polylactic acid-polycaprolactone (PEG-S-S-PLA-PCL-OH) have been used to deliver bacosides to the brain. Bacosides are classified as triterpenoid saponins and are used in Indian Ayurveda for reversal of amnesia; however, no study has extensively demonstrated their efficacy as a nano-formulation in an animal model. The polymer was synthesized by ring opening polymerization of lactide and ε-caprolactone. The nanoparticles obtained by nanoprecipitation showed a core-shell morphology, with an average size of 110 nm, by transmission electron microscopy (TEM). The colloidal stability, hemocompatibility and cytocompatibility of the polymersomes proved their biocompatibility. pH and disulfide linkages in the polymeric chain accelerated the disintegration of the polymersomes at pH 6.6 and at pH 6.6 with glutathione (GSH) in comparison to pH 7.4, supporting their degradation behavior. Supermagnetic iron oxide nanoparticles (SPIONs, 74.99 μg mg-1 polymer) encapsulated into the polymersomes demonstrated their uptake in a mouse model by MRI. Furthermore, bacosides encapsulated in the polymersomes (10% loading) showed significant memory loss reversal in chemically induced amnesic mice, supported by the gene expression profiles of Arc, BDNF and CREB as well as by histopathology.

Anti-Radical and Neuroprotective Potential of &amp;lt;i&amp;gt;Ficus infectoria&amp;lt;/i&amp;gt; in Scopolamine Induced Memory Impairment in Mice

Ficus infectoria has a wide distribution in Bangladesh, Nepal, Pakistan, Sri Lanka, Southwest China and Indochina and is an enrich source of phytochemicals thereby possess antibacterial, antifungal and hyperglycaemic activities. In this study, we attempted to examine the cognitive ability of methanolic and ethanolic extract of F. infectoria fruit extract in scopolamine induced memory impairment in mice by using preliminary phytochemical and antioxidant tests, and the cognitive ability of the methanolic and ethanolic fruit extract of F. infectoria. Fruit extract was analyzed in scopolamine amnesia mice using passive avoidance approach. Piracetam was used as a reference drug (200 mg/Kg). Further confirmation was provided by means of mice brain homogenate biochemical tests. Maximum phytochemical, antioxidant activity and nootropic ability were observed in the ethanolic fruit extract of F. infectoria. Plant extract was used at three doses i.e. 75 mg/Kg, 150 mg/Kg and 300 mg/Kg and exhibited nootropic abilities in all tests used. Enhanced SDL value i.e. (291.2 ± 0.33+++###) was observed by the administration of plant extract at all dose range in comparison to reference drug i.e. piracetam (252.8 ± 1.60###) used in the study. The plant extract utilization has showed increase in total protein (25.08 ± 0.26+++### mg/g of tissue) and reduced glutathione content (33.0 ± 0.46+++### nmoles/mg of protein) and vice versa while low malondialehyde (MDA) (9.18 ± 0.17+++### nmoles/mg of protein) and AChE activity (0.067 ± 0.009+++### M/min/g protein). However, opposite situation was observed in the scopolamine amnesia mice. Hence it was concluded the plant extract possessed neuroprotective activity in the scopolamine induced cognitive decline in mice thereby used as cost effective natural medicines in near future.

20(S)-protopanaxadiol (PPD) alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of Egr-1, c-Fos and c-Jun in mice

20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved. In this study, mice were pretreated with PPD (20 and 40 μmol/kg) and donepezil (1.6 mg/kg) intraperitoneally (i.p) for 14 days. Then, open field test was used to assess the effect of PPD on the locomotor activity and mice were daily injected with SCOP (0.75 mg/kg) to induce cognitive deficits and then subjected to behavioral tests by object location recognition (OLR) experiment and Morris water maze (MWM) task. The cholinergic system function, oxidative stress biomarkers and protein expression of Egr-1, c-Fos, and c-Jun in mouse hippocampus were examined. PPD was found to significantly improve the performance of amnesia mice in OLR and MWM tests. PPD regulated cholinergic function by inhibiting SCOP-induced elevation of acetylcholinesterase (AChE) activity, decline of choline acetyltransferase (ChAT) activity and decrease of acetylcholine (Ach) level. PPD suppressed oxidative stress by increasing activities of antioxidant enzymes such as superoxide dismutase (SOD) and lowering maleic diadehyde (MDA) level. Additionally, PPD significantly elevated the expression of Egr-1, c-Fos, and c-Jun in hippocampus at protein level. Taken together, all these results suggested that 20(S)-protopanaxadiol (PPD) may be a candidate compound for the prevention against memory loss in some neurodegenerative diseases such as Alzheimer's disease (AD).