Scopolamine-induced Memory Impairment Research Articles

Fermented rice peptides attenuate scopolamine-induced memory impairment in mice by regulating neurotrophic signaling pathways in the hippocampus

This study investigated the preventive effects of fermented rice peptides (FRPs) against scopolamine-induced memory impairment in mice and their potential mechanisms. Mice were pretreated with FRPs (25 and 100 mg/kg body weight) via intraperitoneal injection for 7 days, followed by intraperitoneal injection of scopolamine. FRP pretreatment suppressed scopolamine-induced cognitive impairment in passive-avoidance test and significantly upregulated levels of brain-derived neurotrophic factor (BDNF) and induced the phosphorylation of cAMP response element binding (CREB) protein and extracellular signal-regulated kinase (ERK) in the hippocampus of scopolamine-treated mice. Additionally, scopolamine-treated mice showed significantly decreased acetylcholine levels and increased acetylcholine-esterase activity in the hippocampus as compared with controls; however, these changes were suppressed by FRP pretreatment. Among the fractions separated by size-exclusion chromatography, the non-glycosylated peptide fraction of FRP suppressed H2O2-induced neuronal damage in SK-N-SH cells via upregulated BDNF levels. Our findings demonstrated that FRP prevented memory impairment, and that the underlying mechanism might involve regulation of the ERK/CREB/BDNF signaling pathway. These results suggest FRP as a potential agent for the prevention of age-related cognitive decline and dementia.

Elaeagnus glabra f. oxyphylla Attenuates Scopolamine-Induced Learning and Memory Impairments in Mice by Improving Cholinergic Transmission via Activation of CREB/NGF Signaling

We aimed to investigate the therapeutic effects of an Elaeagnus glabra f. oxyphylla (EGFO) ethanol extract in mice with scopolamine-induced memory dysfunction. Fifty male mice were randomly divided into a normal control group, a scopolamine-treated group, a scopolamine and EGFO extract-treated group, and a scopolamine and tacrine-treated group. EGFO (50 or 100 mg/kg/day) was received for 21 days. Step-through passive avoidance and Y-maze tests were performed to examine the effects of treatment on learning and memory impairments. Acetylcholine (Ach) levels and acetylcholinesterase (AchE) activity were measured via an enzyme-linked immunosorbent assay (ELISA). Levels of choline acetyltransferase (ChAT), nerve growth factor (NGF), cAMP response element-binding protein (CREB), and apoptosis-related protein expression were determined via Western blot analysis. EGFO pretreatment significantly attenuated scopolamine-induced memory impairments, relative to findings observed in the scopolamine-treated group. Levels of cholinergic factors in the brain tissues were markedly attenuated in the scopolamine-treated group. EGFO treatment also attenuated neural apoptosis in scopolamine-treated mice by decreasing the expression of apoptosis-related proteins such as Bax, Bcl2, cleaved caspase-3, and TUNEL staining. These results suggest that EGFO improves memory and cognition in a mouse model of memory impairment by restoring cholinergic and anti-apoptotic activity, possibly via activation of CREB/NGF signaling.

Neuroprotective effects of novel nanosystems simultaneously loaded with vinpocetine and piracetam after intranasal administration

AimsThe study aim was to test the efficacy of a novel created hybrid nanosystem compared to other nanosystems in treatment of scopolamine induced memory impairment. Main methodsThe fabrication and characterization of nanoformulations (microemulsion, liposomes, ethosomes, transfersomes and transethosomes) coencapsulating two cognitive enhancers; piracetam and vinpocetine delivered intranasally, in addition to a novel nanocomposite microemulsion/vesicular nanoformulation was described. Key findingsFormulations delivered the drugs across sheep nasal mucosa, with cumulative percentage reaching 29.99% for vinpocetine and 57.78% for piracetam. While the solution form of the drugs was totally ineffective, the selected transethosomal, microemulsion and nanocomposite formulations reversed the scopolamine induced effect on the step through latency of passive avoidance test and the spontaneous alternation behavior in Y maze test, further confirmed by histopathlogical examination. All three nanoformulations significantly decreased the acetylcholinesterase activity and the extent of lipid peroxidation by 32–42%. The nanocomposite formulation was superior to the microemulsion and transethosomal formulations in its anti-inflammatory and antiapoptotic effects, delineated by higher extent of inhibition of COX-2 and caspase 3 expression respectively. SignificanceResults support the hypothesis that the novel microemulsion/vesicular nanocomposite system is a promising neuroprotective modality for intranasal brain targeting which is worthy of exploitation in other brain diseases.

Cortico-hippocampal memory enhancing activity of hesperetin on scopolamine-induced amnesia in mice: role of antioxidant defense system, cholinergic neurotransmission and expression of BDNF.

Alzheimer disease (AD) is an age related neurodegenerative disease causing severe cognitive and memory decline in elderly people. Flavonoids play neuroprotective role by inhibiting and/or modifying the self-assembly of the amyloid-β (Aβ) or tau peptide into oligomers and fibrils. This study sought to investigate the effect of hesperetin (HPT) on scopolamine-induced memory impairments in mice. Mice were orally pretreated with HPT (1, 5 or 50mg/kg) or vehicle (normal saline; 10ml/kg) for 3 consecutive days. One hour post-treatment on day 3, scopolamine (3mg/kg, i.p.) was administered 5min before locomotor activity (open field test) and memory function (novel object recognition test (NORT) for 2 consecutive days and Morris water maze task (MWM) for 5 consecutive days). Levels of oxidative stress markers / brain derived neurotrophic factors (BDNF) and acetylcholinesterase activity were determined in the hippocampus and prefrontal cortex after completion of MWM task. Scopolamine caused no significant change in mice exploration of the familiar or novel object in the test session whereas the HPT-treated mice spent more time exploring the novel object more than familiar object in NORT. Scopolamine also increased the escape latency in acquisition phase and decreases time spent in target quadrant in probe phase which were ameliorated by the pretreatment with HPT. Scopolamine-induced alteration of oxidant-antioxidant balance, acetylcholinesterase activity and neurogenesis in the hippocampus and prefrontal cortex were attenuated by HPT treatment. This study showed that HPT ameliorated non-spatial/spatial learning and memory impairment by scopolamine possibly through enhancement of antioxidant defense, cholinergic and BDNF signaling.

Sulforaphane-Enriched Broccoli Sprouts Pretreated by Pulsed Electric Fields Reduces Neuroinflammation and Ameliorates Scopolamine-Induced Amnesia in Mouse Brain through Its Antioxidant Ability via Nrf2-HO-1 Activation

Activated microglia-mediated neuroinflammation plays a key pathogenic role in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ischemia. Sulforaphane is an active compound produced after conversion of glucoraphanin by the myrosinase enzyme in broccoli (Brassica oleracea var) sprouts. Dietary broccoli extract as well as sulforaphane has previously known to mitigate inflammatory conditions in aged models involving microglial activation. Here, we produced sulforaphane-enriched broccoli sprouts through the pretreatment of pulsed electric fields in order to trigger the biological role of normal broccoli against lipopolysaccharide-activated microglia. The sulforaphane-enriched broccoli sprouts showed excellent potency against neuroinflammation conditions, as evidenced by its protective effects in both 6 and 24 h of microglial activation in vitro. We further postulated the underlying mechanism of action of sulforaphane in broccoli sprouts, which was the inhibition of an inflammatory cascade via the downregulation of mitogen-activated protein kinase (MAPK) signaling. Simultaneously, sulforaphane-enriched broccoli sprouts inhibited the LPS-induced activation of the NF-κB signaling pathway and the secretions of inflammatory proteins (iNOS, COX-2, TNF-α, IL-6, IL-1β, PGE2, etc.), which are responsible for the inflammatory cascades in both acute and chronic inflammation. It also upregulated the expression of Nrf2 and HO-1 in normal and activated microglia followed by the lowered neuronal apoptosis induced by activated microglia. Based on these results, it may exhibit anti-inflammatory effects via the NF-κB and Nrf2 pathways. Interestingly, sulforaphane-enriched broccoli sprouts improved the scopolamine-induced memory impairment in mice through Nrf2 activation, inhibiting neuronal apoptosis particularly through inhibition of caspase-3 activation which could lead to the neuroprotection against neurodegenerative disorders. The present study suggests that sulforaphane-enriched broccoli sprouts might be a potential nutraceutical with antineuroinflammatory and neuroprotective activities.

Inhibition of Oxidative Neurotoxicity and Scopolamine-Induced Memory Impairment by γ-Mangostin: In Vitro and In Vivo Evidence.

Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L. (Guttifereae), α- and γ-mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of γ-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of γ-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of α-mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered γ-mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that γ-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, α-mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that γ-mangostin, not α-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only γ-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited β-secretase activity. Furthermore, we observed that the oral administration of γ-mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of γ-mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, γ-mangostin could serve as a potentially preferable candidate over α-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer's disease.

Agathisflavone isolated from Schinus polygamus (Cav.) Cabrera leaves prevents scopolamine-induced memory impairment and brain oxidative stress in zebrafish (Danio rerio)

BackgroundAgathisflavone, a biflavonoid isolated from Schinus polygamus (Cav.) Cabrera leaves been reported to promote various biological activities such as anti-inflammatory properties, promoting cognition and preventing cancer, antioxidant and antiapoptotic activities. PurposeHere, we tested the hypothesis whether anxiety, amnesia, and brain oxidative stress induced by scopolamine could be counteracted in zebrafish model by agathisflavone and tried to ascertain the underlying mechanism. MethodsAgathisflavone (1, 3 and 5 µg/l) was administered by immersion to zebrafish once daily for 8 days period. Anxiety and memory impairment were induced with scopolamine (100 µM) and measured with the novel tank diving test (NTT) and the Y-maze test. Zebrafish were divided into seven groups (n = 20/group): first group - control, second group - scopolamine (100 μM), the third, fourth and fifth group - agathisflavone treatment groups (FAB, 1 µg/l, 3 µg/l, and 5 µg/l), the sixth group - imipramine (IMP, 20 mg/l, as the positive control in NTT test), and the seventh group - donepezil group (DP, 10 mg/l, as the positive control in Y-maze test). The identification of the agathisflavone was done by spectroscopy, and the structure of the compound was confirmed by (-) Electrospray Ionisation Mass Spectrometry (ESI-MS). The brain oxidative status and acetylcholinesterase (AChE) activity were also investigated. ResultsAgathisflavone from Schinus polygamus (Cav.) Cabrera leaves was identified. Also, we demonstrated that agathisflavone significantly reversed scopolamine-induced behavioral score alteration in the NTT and Y-maze tests. Consequently, agathisflavone promoted inhibition of AChE activity and restored the brain antioxidant status. ConclusionOur results demonstrate that agathisflavone promotes brain antioxidant action and ameliorates scopolamine-induced anxiety and memory deficits in zebrafish.

Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice.

Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.

Effect of ethanolic extract of leaves of Solanum trilobatum on scopolamine-induced memory impairment in Sprague Dawley rats

Objective: The objective of the study is to determine the effect of ethanolic extract of leaves of Solanum trilobatum (EEST) on scopolamine-induced memory impairment in Sprague Dawley (SD) rats. Materials and Methods: The leaves of S. trilobatum were extracted with ethanol and used for the study. The SD rats were divided into six groups each consist of six animals, namely normal control; scopolamine control; donepezil treated 3 mg/kg; and EEST treated 100, 200, and 400 mg/kg, respectively. Except normal control, all other animals were administered with intraperitoneal injection of scopolamine (1 mg/kg body weight) for 21 days to induce memory impairment. Donepezil and EEST were administered once daily through oral gavage for 21 consecutive days. On prestudy, 7th, 14th, and 21st days of the experiment, the animals' locomotor activity, muscle grip strength and escape latency time (ELT) were measured. At the end of the study, blood samples were collected from all the animals and they were sacrificed; the organs such as brain, liver, lung, heart, kidney, and stomach were harvested, and absolute organ weight was measured. Blood samples were used for the biochemical analysis. Results: The rats treated with EEST 100, 200, and 400 mg/kg did not show any change in locomotor activity and grip strength and significantly reduced motor resistance. The animals treated with donepezil showed a significant reduction in ELT. The animals treated with EEST 100 and 200 mg/kg showed significant increases in ELT, whereas animals treated with EEST 400 mg/kg did not show significant changes in ELT compared with that of prestudy. At the end of the study, EEST-treated animals did not show significant changes in biochemical parameters, whereas donepezil-treated animals showed a significant increase in cholesterol level compared with control animals. Furthermore, EEST did not affect regular body weight gain, absolute and relative organ weight. Conclusion: EEST did not show neuroprotective effect at lower doses in rats, but the high dose (400 mg/kg) prevented scopolamine-induced memory impairment, and this effect is not significant when compared with standard donepezil.

Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats

IntroductionWe investigated the effects of zerumbone (1 and 10 mg/kg) against hyperactivity, anxiety and memory impairment in scopolamine-induced dementia in Sprague-Dawley rats. MethodsOpen field tests, elevated plus maze and Morris water maze were performed to assess general locomotor activity, anxiety-like behaviours and learning and memory processes respectively in rats pretreated with scopolamine. ResultsScopolamine-treated rats showed high total activity, stereotype, and total distance travelled in the open field arena, reduced number of entries to open arms, decreased the percentage of time spent in open arms and higher escape latency time in the Morris water maze test. Interestingly, single administration of zerumbone (1 and 10 mg/kg) reversed the hyperactivity, anxiety-like behaviours, and learning impairment effects of scopolamine in the three experimental model studied respectively. DiscussionOur findings demonstrated that the scopolamine-induced impairment of learning and memory was reversed by the administration of zerumbone. As a conclusion, our findings presented the positive effects of zerumbone on dementia-like behaviours in the animal model used and could possibly contribute for future research to manage hyperactivity, anxiety, and learning disabilities.

Safflower (Carthamus tinctorius L.) seed attenuates memory impairment induced by scopolamine in mice via regulation of cholinergic dysfunction and oxidative stress.

Cholinergic dysfunction and oxidative stress are the most common causes of Alzheimer's disease (AD). Safflower seed contains various anti-oxidant and cholinergic improvement compounds, such as serotonin and its derivatives. In the present study, we investigated the protective effects and mechanisms of a safflower seed extract on scopolamine-induced memory impairment in a mouse model. The safflower seed extract was orally administered at a dose of 100 mg kg-1 day-1, and then behavior tests (such as T-maze and novel object recognition tests) were conducted. Acetyl cholinesterase (AChE) activity, reactive oxygen species (ROS) production, and antioxidant enzymes in the brain were measured. In behavior tests, the novel route exploration and object recognition were improved by the administration of the safflower seed extract, which suggests that the safflower seed extract improves memory function in the scopolamine-treated mouse model. In addition, the safflower seed extract-administered group showed inhibition of the AChE activity and improved cholinergic dysfunction. Furthermore, the administration of the safflower seed extract resulted in lower ROS production and higher antioxidant enzyme levels as compared to the scopolamine-treated group, suggesting the protective role of the safflower seed extract against oxidative stress. The results of the present study suggest that the safflower seed extract improves scopolamine-induced memory deficits via the inhibition of cholinergic dysfunction and oxidative stress. Therefore, safflower seeds might become a promising agent for memory improvement in AD patients.

Pharmacological evaluation of Hibiscus abelmoschus against scopolamine-induced amnesia and cognitive impairment in mice

Objective: Progressive loss of memory has a prominent role in devastating neurodegenerative diseases such as amnesia, dementia and Alzheimer's disease. The present study was, thus, designed to investigate the potential of Hibiscus abelmoschus (H. abelmoschus) in scopolamine-induced amnesic Swiss Albino mice. Materials and Methods: Phytochemical and acute toxicity studies of H. abelmoschus ethanolic extract (HAEE) were performed. Memory loss was induced by scopolamine (1 mg/kg, i.p), a muscarinic antagonist, and evaluated by using Morris water maze (MWM), elevated plus maze (EPM) and modified passive avoidance tests on Swiss Albino mice. Besides this, locomotor activity, serum biochemical parameters such as total cholesterol and triglyceride levels were evaluated. Lipid peroxidation (LPO), glutathione (GSH) level and catalase (CAT) activity were also checked. HAEE at a dose of 200 and 400 mg/kg body weight administered orally to the animals. Donepezil hydrochloride (1 mg/kg) was taken as standard. Results: Pre-treatment of mice with HAEE significantly reversed scopolamine-induced memory impairments, as evidenced by a significant decrease in escape latency in the MWM task, transfer latency in EPM task and an increase in step-down latency in the modified passive avoidance task. HAEE also exhibited a remarkable cholesterol and triglyceride-lowering property in the present study. Moreover, treatment with HAEE (200 and 400 mg/kg, p.o) to scopolamine-induced rats significantly decreased the LPO and increased the GSH and catalase levels. Conclusion: The memory restorative effects of H. abelmoschus in amnesia may involve its multiple functions including antioxidative and lipid-lowering properties and the presence of phytoconstituents. Thus, H. abelmoschus may act as memory enhancer and may also be useful as a supportive adjuvant in the treatment of impaired memory functions.

Scopolamine 유발 기억 손상 마우스 모델에서 국산 산사와 중국산 산사의 항건망 효과 비교

Scopolamine 유발 기억 손상 마우스 모델에서 국산 산사와 중국산 산사의 항건망 효과 비교

The Effect of Ethanol Extract of Beta vulgaris Leaves on Rats with Scopolamine-Induced Cognitive Deficiency

Background: The current study evaluated the effect of ethanol extract of Beta vulgaris leaves on scopolamine-induced memory impairments. Methods: Animals were randomly divided into five groups including 10 rats. The control group received distillated water, the scopolamine group received scopolamine (1 mg/kg, intraperitoneally (IP) daily for 15 days. The extract-treated groups received B. vulgaris leaves extract at 50, 100, and 200 mg/kg IP 30 minutes after administration of scopolamine. After a 15-day treatment, passive avoidance memory, brain antioxidant capacity, and malondialdehyde (MDA) level were evaluated in each rat. Results: Scopolamine-treated rats showed shorter step-through latency (STL) than the control rats, but not significantly (P > 0.05). Groups treated with 100 and 200 mg/kg of B. vulgaris leaf extract had significantly longer STL than scopolamine-treated rats (P < 0.05). Administration of B. vulgaris leaf extract (200 mg/kg) into scopolamine-treated rats significantly improved brain antioxidant capacity. Conclusions: The results of the current study indicated that the ethanol B. vulgaris extract at 200 mg/kg showed positive activity against the adverse effects of scopolamine.

The Effect of Intrahippocampal Insulin Injection on Scopolamine-induced Spatial Memory Impairment and Extracellular Signal-regulated Kinases Alteration.

Introduction:It is well documented that insulin has neuroprotective and neuromodulator effects and can protect against different models of memory loss. Furthermore, cholinergic activity plays a significant role in memory, and scopolamine-induced memory loss is widely used as an experimental model of dementia. The current study aimed at investigating the possible effects of insulin against scopolamine-induced memory impairment in Wistar rat and its underlying molecular mechanisms.Methods:Accordingly, animals were bilaterally cannulated in CA1, hippocampus. Intrahippocampal administration of insulin 6 MU and 12 MU in CA1 per day was performed during first 6 days after surgery. During next four days, the animal’s spatial learning and memory were assessed in Morris water maze test (three days of learning and one day of retention test). The animals received scopolamine (1 mg/kg) Intraperitoneally (IP) 30 minutes before the onset of behavioral tests in each day. In the last day, the hippocampi were dissected and the levels of MAPK (mitogen-activated protein kinases) and caspase-3 activation were analyzed by Western blot technique.Results:The behavioral results showed that scopolamine impaired spatial learning and memory without activating casapase-3, P38, and JNK, but chronic pretreatment by both doses of insulin was unable to restore this spatial memory impairment. In addition, scopolamine significantly reduced Extracellular signal-Regulated Kinases (ERKs) activity and insulin was unable to restore this reduction. Results revealed that scopolamine-mediated memory loss was not associated with hippocampal damage.Conclusion:Insulin as a neuroprotective agent cannot restore memory when there is no hippocampal damage. In addition, the neuromodulator effect of insulin is not potent enough to overwhelm scopolamine-mediated disruptions of synaptic neurotransmission.

Lactobacillus johnsonii CJLJ103 Attenuates Scopolamine-Induced Memory Impairment in Mice by Increasing BDNF Expression and Inhibiting NF-��B Activation

In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ) could alleviate cholinergic memory impairment in mice. Oral administration of LJ alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression and CREB phosphorylation in the hippocampi of the brain, as well as suppressed TNF-α expression and NF-κB activation. LJ also increased BDNF expression in corticosterone-stimulated SH-SY5Y cells and inhibited NF-κB activation in LPS-stimulated microglial BV2 cells. However, LJ did not inhibit acetylcholinesterase activity. These findings suggest that LJ, a member of human gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF expression and inhibiting NF-κB activation.

Amelioration of Cognitive Deficit by Embelin in a Scopolamine-Induced Alzheimer's Disease-Like Condition in a Rat Model.

Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) is one of the active components (2.3%) found in Embelia ribes Burm fruits. As determined via in vitro AChE inhibition assay, embelin can inhibit the acetylcholinesterase enzyme. Therefore, embelin can be utilized as a therapeutic compound, after further screening has been conducted for its use in the treatment of Alzheimer’s disease (AD). In this study, the nootropic and anti-amnesic effects of embelin on scopolamine-induced amnesia in rats were evaluated. Rats were treated once daily with embelin (0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg) and donepezil (1 mg/kg) intraperitoneally (i.p.) for 17 days. During the final 9 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. Besides that, behavioral analysis was carried out to assess the rats’ learning and memory functions. Meanwhile, hippocampal tissues were extracted for gene expression, neurotransmitter, and immunocytochemistry studies. Embelin was found to significantly improve the recognition index and memory retention in the novel object recognition (NOR) and elevated plus maze (EPM) tests, respectively. Furthermore, embelin at certain doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) significantly exhibited a memory-enhancing effect in the absence of scopolamine, besides improving the recognition index when challenged with chronic scopolamine treatment. Moreover, in the EPM test, embelin treated rats (0.6 mg/kg) showed an increase in inflection ratio in nootropic activity. However, the increase was not significant in chronic scopolamine model. In addition, embelin contributed toward the elevated expression of BDNF, CREB1, and scavengers enzymes (SOD1 and CAT) mRNA levels. Next, pretreatment of rats with embelin mitigated scopolamine-induced neurochemical and histological changes in a manner comparable to donepezil. These research findings suggest that embelin is a nootropic compound, which also possesses an anti-amnesic ability that is displayed against scopolamine-induced memory impairment in rats. Hence, embelin could be a promising compound to treat AD.

Antioxidant hydrolyzed peptides from Manchurian walnut (Juglans mandshurica Maxim.) attenuate scopolamine-induced memory impairment in mice.

Walnut protein, which is obtained as a by-product of oil expression, has not been used efficiently. Although walnuts are beneficial for cognitive functioning, the potential of their protein composition in strengthening learning and memory functions remains unknown. In this study, the inhibition of memory impairment by the Manchurian walnut hydrolyzed peptide (MWHP) was evaluated. Small-molecular-weight MWHP (<3 kDa) achieved the optimal antioxidative activity. Therefore, MWHP (<3 kDa) was subjected to the following mice trials to evaluate its attenuation effect on memory impairment. In the Morris water maze test, MWHP shortened the total path for searching the platform, reduced the escape latency, and increased the dwelling distance and time in the coverage zone. MWHP also prolonged the latency and diminished errors in the passive avoidance response tests. These behavioral tests demonstrated that MWHP could inhibit scopolamine-induced memory impairment. MWHP improved memory by reducing oxidative stress, inhibiting apoptosis, regulating neurotransmitter functions, maintaining hippocampal CA3 pyramidal neurons, and increasing calmodulin-dependent protein kinase II levels in brain tissues. Experimental results proved that MWHP exhibits potential in improving memory and should be used to develop novel functional food. © 2018 Society of Chemical Industry.

DOCOSAHEXAENOIC ACID ADMINISTRATION AMELIORATES SCOPOLAMINE-INDUCED MEMORY IMPAIRMENT IN MICE

Objective: The main objective of this work was to study the memory-enhancing activity of docosahexaenoic acid (DHA) supplementation in normal memory function and scopolamine-induced impaired memory in mice.Methods: The gum acacia suspension of DHA was administered by gavage at the dose of 200 and 300 mg/kg in mice for 30 days to evaluate memory-enhancing potential on normal and scopolamine-induced impaired memory in albino mice. Escape latency in Morris water maze (MWM) and transfer latency (TL) in elevated plus maze (EPM) were recorded, respectively. Mice were given four trial sessions per day to locate the platform for 4 days in MWM model. Scopolamine 1 mg/kg was injected i.p. to produce memory impairment in mice.Result: DHA suspension at the dose of 300 mg/kg showed significant reduction of escape latency and TL as compared to control group, and the effect was comparable to that of standard nootropic agent piracetam at the dose of 100 mg/kg in normal and scopolamine-treated mice. However, DHA at the dose of 200 mg/kg showed significant memory-enhancing effect in only scopolamine-induced impaired memory model.Conclusion: The study revealed that the chronic administration of DHA exhibited significant memory-enhancing activity against both normal as well as scopolamine-treated impaired memory mice groups, however, this effect was more marked on scopolamine-induced memory impairment as compared to normal memory function.

Beneficial effects of Urtica dioica on scopolamine-induced memory impairment in rats: protection against acetylcholinesterase activity and neuronal oxidative damage

This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3–5) the plant extract (20, 50, or 100 mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control. Scopolamine decreased the latency to enter the dark in passive avoidance test. Besides, it also increased AChE activity and malondialdehyde (MDA) concentration in the hippocampal and cortical tissues while decreased thiols content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain (p < 0.01–p <0.001). Treatment by the extract reversed all the effects of scopolamine (p < 0.05–p <0.001). According to the results of present study, the beneficial effects of U. dioica on memory can be attributed to its protective effects on oxidative damage of brain tissue and AChE activity.