Scopolamine-induced Memory Impairment In Mice Research Articles

Blackcurrant (Ribes nigrum L.) improves cholinergic signaling and protects against chronic Scopolamine-induced memory impairment in mice.

Blackcurrant (Ribes nigrum L.) is a berry rich in anthocyanins, bioactive compounds known for their antioxidant and neuroprotective properties that benefit human health. This study aimed to investigate the effects of blackcurrant and its association with Donepezil on memory impairment, cholinergic neurotransmission, and antioxidant systems in a mouse model of amnesia induced by chronic administration of Scopolamine. Adult male Swiss mice were given saline, blackcurrant (50 mg/kg, orally), and/or Donepezil (5 mg/kg, orally) and/or Scopolamine (1 mg/kg, intraperitoneally). Behavioral tests revealed that blackcurrant and/or Donepezil prevented the learning and memory deficits induced by Scopolamine. In the cerebral cortex and hippocampus, blackcurrant and/or Donepezil treatments prevented the increase in acetylcholinesterase and butyrylcholinesterase activities induced by Scopolamine. Scopolamine also disrupted the glutathione redox system and increased levels of reactive species; nevertheless, blackcurrant and/or Donepezil treatments were able to prevent oxidative stress. Furthermore, these treatments prevented the increase in gene expression and protein density of acetylcholinesterase and the decrease in gene expression of the choline acetyltransferase enzyme induced by Scopolamine. Findings suggest that blackcurrant and Donepezil, either alone or in combination, have anti-amnesic effects by modulating cholinergic system enzymes and improving the redox profile. Therefore, blackcurrant could be used as a natural supplement for the prevention and treatment of memory impairment in neurodegenerative diseases.

Protocatechuic Acid from Euonymus alatus Mitigates Scopolamine-Induced Memory Impairment in Mice.

The increasing prevalence of age-related neurodegenerative disorders owing to the aging population worldwide poses substantial challenges. This study investigated the neuroprotective effects of protocatechuic acid (PCA), a compound found in various fruits, vegetables, and grains, using a scopolamine-induced hypomnesia mouse model. Six-week-old male C57BL/6J mice were orally administered PCA at doses of 10 and 100 mg/kg body weight per day for two weeks, along with intraperitoneal injections of scopolamine. Learning and memory abilities were assessed using the passive avoidance, Morris water maze, and Y-maze behavioral assays. Biochemical analyses evaluated the levels of oxidative stress markers, including 8-hydroxydeoxyguanosine (8-OHdG) in the blood and malondialdehyde (MDA) in the brain, as well as phase II antioxidant proteins in the hippocampus. Histological examination was conducted to determine hippocampal integrity. Our results demonstrated that PCA administration at 10 mg/kg body weight per day or higher for two weeks (i) significantly ameliorated scopolamine-induced learning and memory impairments, as evidenced by improved performance in behavioral tasks, (ii) reduced plasma 8-OHdG levels and cerebral MDA levels in a dose-dependent manner, (iii) increased antioxidant protein expressions in the hippocampal tissue, and (iv) mitigated histological damage in the hippocampal region of the brain. These findings suggest that oral administration of PCA provides neuroprotective effects against oxidative stress-induced learning and memory impairments, possibly through upregulating antioxidant machinery. Therefore, PCA may serve as a promising dietary supplement for mitigating cognitive deficits associated with neurodegenerative diseases.

Walnut-Derived Peptides Ameliorate Scopolamine-Induced Memory Impairments in a Mouse Model via Activation of Peroxisome Proliferator-Activated Receptor γ-Mediated Excitotoxicity.

We investigated the protective effect of walnut peptides and YVPFPLP (YP-7) on scopolamine-induced memory impairment in mice and β-amyloid (Aβ)-induced excitotoxic injury in primary hippocampal neurons, respectively. Additionally, the protective mechanism of YP-7 on neuronal excitotoxicity was explored. Mouse behavioral and hippocampal slice morphology experiments indicate that YP-7 improves the learning and memory abilities of cognitively impaired mice and protects synaptic integrity. Immunofluorescence, western blotting, and electrophysiological experiments on primary hippocampal neurons indicate that YP-7 inhibits neuronal damage caused by excessive excitation of neurons induced by Aβ. HT-22 cell treatment with peroxisome proliferator-activated receptor γ (PPARγ) activators and inhibitors showed that YP-7 activates PPARγ expression and maintains normal neuronal function by forming stable complexes with PPARγ to inhibit the extracellular regulated protein kinase pathway. Therefore, YP-7 can ameliorate glutamate-induced excitotoxicity and maintain neuronal signaling. This provides a theoretical basis for active peptides to ameliorate excitotoxicity and the development of functional foods.

Folic acid ameliorated the scopolamine-induced memory impairment in mice and the neuroprotective mechanisms

Current research on the neuroprotective regulatory mechanism of folic acid (FA) is limited to a single DNA methylation pathway. Consequently, this study aimed to explore the neuroprotective effect of FA on memory-impaired mice and its molecular mechanism. This study explored the preventive function of FA in enhancing memory impairment in scopolamine-induced mice using behavioral tests, histological staining techniques, Fourier transform infrared microscopy, immunofluorescence, and Western blotting. We found that FA improved behavioral performance, ameliorated oxidative stress, repaired neuronal damage in hippocampal CA1, CA3 regions and increased the number of Nissl body, increased unsaturated lipid levels, and activated long-term potentiation (LTP) pathway (p-CaMKII, p-CREB, BDNF) and synaptic plasticity (PSD95, Syn) in mice, which indicated that FA mitigates scopolamine-induced memory impairment by suppressing oxidative stress, upregulating the LTP pathway, and enhancing unsaturated lipid levels. These results suggested a preventive and dose-dependent effect of folic acid on memory impairment.

Vanillin derivatives as antiamnesic agents in scopolamine-induced memory impairment in mice

Amnesia is a major health problem prevalent in almost every part of the world specifically in old age peoples. Vanillin analogues have played an important role in the field medicines. Some of them have been documented to be promising inhibitors of cholinesterases and could therefore, be used as antidepressant, anti-Alzheimer and as neuroprotective drugs. In this connection, the present study was designed to synthesize new vanillin analogues (SB-1 to SB-6) of varied biological potentials. The synthesized compounds were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and as scavengers of DPPH and ABTS free radicals followed by behavioural antiamnesic evaluation in mice. The compounds; SB-1, SB-3, SB-4 and SB-6 more potently inhibited AChE with IC50 values of 0.078, 0.157, 0.108, and 0.014 μM respectively. The BChE was more potently inhibited by SB-3 with IC50 of 0.057 μM. Moreover, all of the tested compounds exhibited strong antioxidant potentials with promising results of SB-3 against DPPH with IC50 of 0.305 μM, while SB-5 was most active against ABTS with IC50 of 0.190 μM. The in-vivo studies revealed the improvement in memory deficit caused by scopolamine. Y-Maze and new object recognition test showed a considerable decline in cognitive dysfunctions. In Y-Maze test the spontaneous alteration of 69.44 ± 1% and 84.88 ± 1.35% for SB-1 and 68.92 ± 1% and 80.89 ± 1% for SB-3 at both test doses were recorded while during the novel object recognition test the Discrimination Index percentage of SB-1 was more pronounced as compared to standard drug. All compounds were found to be potent inhibitors of AChE, BChE, DPPH, and ABTS in vitro however, SB-1 and SB-3 were comparatively more potent. SB-1 was also more active in reclamation of memory deficit caused by scopolamine. SB-1 and SB-3 may be considered as excellent drug candidates for treating amnesia subjected to toxicological evaluations in other animal models.

The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aβ(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aβ(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Scopolamine-Induced Memory Impairment in Mice: Effects of PEA-OXA on Memory Retrieval and Hippocampal LTP.

Transient global amnesia, both persistent and transient, is a very common neuropsychiatric syndrome. Among animal models for amnesia and testing new drugs, the scopolamine test is the most widely used for transient global amnesia (TGA). This study examined the scopolamine-induced deficits in working memory, discriminative memory, anxiety, and motor activity in the presence of intranasal PEA-OXA, a dual antagonist of presynaptic α2 and H3 receptors. Male C57BL/6 mice were treated with intraperitoneal scopolamine (1 mg/kg) with or without pre-treatment (15 min) or post-treatment (15 min) with intranasal PEA-OXA (10 mg/kg). It was seen that scopolamine induced deficits of discriminative and spatial memory and motor deficit. These changes were associated with a loss of synaptic plasticity in the hippocampal dentate gyrus: impaired LTP after lateral entorhinal cortex/perforant pathway tetanization. Furthermore, hippocampal Ach levels were increased while ChA-T expression was reduced following scopolamine administration. PEA-OXA either prevented or restored the scopolamine-induced cognitive deficits (discriminative and spatial memory). However, the same treatment did not affect the altered motor activity or anxiety-like behavior induced by scopolamine. Consistently, electrophysiological analysis showed LTP recovery in the DG of the hippocampus, while the Ach level and ChoA-T were normalized. This study confirms the neuroprotective and pro-cognitive activity of PEA-OXA (probably through an increase in the extracellular levels of biogenic amines) in improving transient memory disorders for which the available pharmacological tools are obsolete or inadequate and not directed on specific pathophysiological targets.

Anticholinesterase and antioxidant activity of Drynaria quercifolia and its ameliorative effect in scopolamine-induced memory impairment in mice

Ethnopharmacological relevanceDrynaria quercifolia is an epiphytic fern distributed all over Bangladesh with traditional use in treating neurological disorders and other ailments. Although several pharmacological activities of D. quercifolia have been investigated, the neuroprotective potential of this plant is still unexplored. Aim of studyIn this study, we evaluated the in vitro anticholinesterase and antioxidant activities of D. quercifolia and the neuroprotective effect in scopolamine-induced memory-impaired mouse model. Materials and methodsThe crude methanol extract (DCM) of the plant was fractionated to prepare n-hexane (DHF), chloroform (DCF), ethyl acetate (DEF), and aqueous (DAF) factions. All the fractions were evaluated for anticholinesterase activity by modified Ellman's method and the antioxidant activity by several in vitro assays such as DPPH and hydroxyl free radicals scavenging, reducing power, and inhibition of brain lipid peroxidation. The effect of the most active fractions (both DCF and DEF) on learning and memory was assessed in scopolamine-induced mouse model of memory-impairment by Morris water maze tasks. Biochemical assays were performed in brain tissue. The active compound was isolated and characterized by chromatographic, spectroscopic, and molecular docking methods. ResultsPhytochemical analysis demonstrated a high content of phenolic and flavonoid in DEF. In vitro studies revealed a strong antioxidant power of DEF and anticholinesterase activity of DCF. Both the DCF and DEF significantly (P˂0.05) reduced the escape latency time in the Morris's water maze tasks, and increased the time spent in the northeast quadrant in the probe trial. Biochemical data demonstrated that treatment with DCF and DEF at different doses significantly (P˂0.0001) inhibited acetylcholinesterase activity, restored GSH levels, and reduced MDA levels in the brain of scopolamine-induced memory-impaired mice, indicating the protective effect of D. quercifolia, possibly by acetylcholinesterase inhibition and oxidative stress prevention. Chromatographic methods of separation led to he isolation of catechin and protocatechuric acid from DEF and 3,4-dihydroxy benzoic acid from DCF. The structure of the compounds was determined by studies of their 1H-NMR spectra. Molecular docking as well as in vitro study suggests the anticholinesterase and antioxidant activity of the isolated compounds. ConclusionOur study suggested that the extracts of D. quercifolia, due to anticholinesterase and antioxidant activity, ameliorate the scopolamine-induced memory impairment in mice and thus may represent therapeutics in the treatment of Alzheimer's disease.

Antiamnesic Effects of Novel Phthalimide Derivatives in Scopolamine-Induced Memory Impairment in Mice: A Useful Therapy for Alzheimer's Disease.

Phthalimides have diverse bioactivities and are attractive molecules for drug discovery and development. Here, we explored new synthesized phthalimide derivatives (compounds 1-3) in improving memory impairment associated with Alzheimer's disease (AD), using in vitro and ex vivo acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition and in vivo models, including Y-maze test and novel object recognition test (NORT). Compounds 1-3 exhibited significant AChE activity with IC50 values of 10, 140, and 18 μM and BuChE with IC50 values of 80, 50, and 11 μM, respectively. All compounds 1-3 showed excellent antioxidant potential in DPPH and ABTS assays with IC50 values in the range of 105-340 and 205-350 μM, respectively. In ex vivo studies, compounds 1-3 also significantly inhibited both enzymes in a concentration-dependent manner along with significant antioxidant activities. In in vivo studies, compounds 1-3 reversed scopolamine-induced amnesia as indicated by a significant increase in the spontaneous alternation in the Y-maze test and an increase in the discrimination index in the NORT. Molecular docking was also conducted for compounds 1-3 against AChE and BuChE, which showed that compounds 1 and 3 have excellent binding with AChE and BuChE as compared to 2. These findings suggest that compounds 1-3 possess significant antiamnesic potential and may serve as useful leads to develop novel therapeutics for the symptomatic management and treatment of AD.

Neuroprotective Property of Tecoma Stans Flower Extract in Scopolamine Induced Amnesia and Chlorpromazine Induced Rigidity in Laboratory Animals

Background and Aim Tecoma stans Linn is an important medicinal plant exhibiting anticancer antioxidant antimicrobial anti-proliferative properties. The present work was designed to investigate the neuroprotective efficacy of methanolic extract of Tecoma stans flowers METSF in laboratory animal models.Methodology The extract of Tecoma stans flowers was investigated against motor coordination test elevated plus maze and by morris water maze. The standard drugs various doses of METSF was administered to experimental animals to assess the motor coordination test using rotarod apparatus retention of memory in mice using elevated plus maze and learning amp memory study by morris water maze.Results The animals administered with drug and METSF showed a increase in muscle grip action on the 0 day 7th day 14th day and 21st day compared to positive control animals. Pretreatment with drug and test extract at different doses showed a reduction of LPO and nitrite levels in brain when compared to positive control animals. On administration of standard and test extract at changed doses showed a marked increase in levels of GSH and Total protein when matched to positive control animals. In elevated plus maze model the Donepezil and METSF of various doses significantly reversed decreased the TL scopolamine-induced memory impairment in mice as compared to scopolamine-treated groups. The scopolamine-administered mice showed a significant improvement in the ELT as compared to normal control group animals. However the administration of METSF at different doses and standard drug Donepezil was found to reduce the ELT significantly as compared to that of scopolamine-treated animals.Conclusion The protective property of METSF may be due to preventing the oxidative stress and potent anti-oxidant property.

Cognitive Enhancing Activity of Fermented Aloe arborescens Extract on Scopolamine-induced Memory Impairment in Mice

Background Alzheimer’s disease (AD) is a type of dementia that leads to loss of memory and learning ability. Aloe arborescens is a traditional medicinal plant in Europe and Africa. It has been reported that A. arborescens showed anti-inflammatory, anti-cancer, antioxidant, and anti-obesity effects. Previously, we reported that fermented A. arborescens extract had neuroprotective activity in glutamate-insulted HT22 cells. Materials and Methods In this study, we evaluated its cognitive enhancing activity by using scopolamine-induced memory impairment in mice as a model system. Morris water maze test was carried out to evaluate spatial memory enhancing activity and a passive avoidance test was performed to evaluate an effect on learning memory. A. arborescens was extracted with methanol in an ultrasonic extraction device and fermented with Lactobacillus brevis. Fermented A. arborescens extract was treated to scopolamine-insulted Institute of Cancer Research (ICR) mice at a concentration of 100, 200, and 300 mg/kg, respectively. Results The fermented A. arborescens extract significantly improved the scopolamine-insulted memory impairment. Fermented A. arborescens extract inhibited acetylcholine esterase activity and boosted brain-derived neurotrophic factor and phosphorylated cAMP-response element-binding protein (p-CREB) expression. These results showed that fermented AA extract improved memory impairment through the increase of the BDNF and p-CREB signal pathway. Conclusion According to these results, we considered that the fermented A. arborescens extract can be a useful candidate for new nutraceuticals for improving memory impairment.

Antarctic krill peptides improve scopolamine-induced memory impairment in mice

The study aims to investigate the repair effects of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) and Ser-Asn-Val-Phe-Asp-Met-Phe (SNVFDMF) peptides on scopolamine-caused memory impairment in mice. Behavioral experiments have revealed that Antarctic krill peptides can ameliorate scopolamine caused memory impairment by changing the behavior of mice. In comparison with the scopolamine group, the two peptides at a dose of 40 mg/kg could improve memory impairment. The serum SOD activity (82.82 ± 0.19 vs 79.47 ± 2.42 U/mg prot) and hippocampal ACh level (101.46 ± 3.23 vs 99.85 ± 7.13 μg/mg prot) of SSDAFFPFR were higher than those of SNVFDMF. Hippocampal AChE activity (0.20 ± 0.03 vs 0.53 ± 0.02 U/mg prot), hippocampal MDA level (1.56 ± 0.01 vs 1.63 ± 0.05 nmol/mg prot) and the serum MDA level (3.38 ± 0.24 vs 3.88 ± 0.21 nmol/mg prot) was lower than that of SNVFDMF. The state of mouse hippocampal cells was further observed by a microscopic imaging system. In addition, western blot analysis showed that SSDAFFPFR could significantly inhibit the expression of Bax, caspase-3, and p53, and promote the expression of BCL-XL, CREB, and BDNF, thus protecting hippocampal neurons in mice. In conclusion, the Antarctic krill peptide can repair scopolamine-induced memory impairment in mice.

Protective Effects of Dapsone on Scopolamine-Induced Memory Impairment in Mice: Involvement of Nitric Oxide Pathway

Introduction: The leading cause of memory impairment is dementia-related disorders. Since current treatments for memory impairment target the neuroinflammatory pathways, we selected dapsone, an anti-inflammatory agent, to evaluate its effects on scopolamine-induced memory impairment in mice and the underlying role of nitric oxide (NO). Methods: Scopolamine (1 mg/kg, intraperitoneal [i.p.]) was used for induction of memory impairment. The animals received various doses of dapsone (0.1, 0.3, 1, 5, and 10 mg/kg, i.p.). Duration and number of arms visits in the Y-maze and step-through latency in the passive-avoidance were documented. To evaluate the underlying signaling pathway, N(ω)-nitro-L-arginine methyl ester (a nonspecific NO synthase [NOS] inhibitor), aminoguanidine (a specific inducible NOS inhibitor), and 7-nitroindazole (a specific neuronal NOS inhibitor) were administered 30 min after dapsone administration. Results: Dapsone (5 mg/kg) substantially improved memory acquisition in scopolamine-induced memory impairment. Additionally, NOS inhibitors considerably reversed the observed neuroprotective effects of dapsone, accompanied by the elevation of NO levels. Conclusion: Dapsone revealed a neuroprotective effect against scopolamine-induced memory impairment in mice, possibly through the nitrergic pathway.

Effects of Moringa oleifera in Two Independents Formulation and as Neuroprotective Agent Against Scopolamine-Induced Memory Impairment in Mice

BackgroundThe cognitive deficit has frequently been found in the elderly population. Several studies have shown that every single part of Moringa oleifera, including leaves, roots, and seeds, has abundant micronutrients, such as flavonoids, which improve the neurobehavioral capacity. However, herb parts that display optimal neuropharmacological properties remain unknown.ObjectiveWe investigate whether M. oleifera seed oil (MOO) or aqueous M. oleifera leaves extracts (MOEs) may ameliorate memory impairment in mice induced with scopolamine (Sco). Additionally, the phytochemical analyses of those two independent formulations were analyzed.MethodsIn this study, 2 ml/kg body weight (BW) of MOO and 500 mg/kg BW of MOE were orally administered to the mice for 28 days, followed by intraperitoneal injection of Sco (1 mg/kg) at the day 22–28 to induce cognitive impairment in those mice.ResultsThe Sco group showed memory retention impairment represented by the Y-maze and novel object recognition tests, significant enhancement of acetylcholine esterase (AChE) activity in hippocampus tissue (p < 0.0001), and increased the level of total antioxidant capacity (TAOC) in serum. Interestingly, the Sco-induced memory defect was improved and completely blunted the AChE exacerbation in Sco+MOO-treated mice (p < 0.0001), although the TAOC level was comparable among the groups. Mechanistically, both tropomyosin receptor kinase B (TrkB), as a brain-derived neurotrophic factor-receptor, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) protein expressions were enhanced with the hippocampus isolated from the Sco group. Nonetheless, pretreatment with MOO only, but not with MOE, ameliorated the enhanced protein expression levels of TrkB and NF-κB (p < 0.05 and p = 0.09, respectively).ConclusionOur data reveal that MOO is preferable to MOE as a neuroprotective as evidenced by improving memory impairment. This effect, at least in part, through inhibiting the AChE and NF-κB activities and modulating the TrkB expression level.

Stephania japonica Ameliorates Scopolamine-Induced Memory Impairment in Mice through Inhibition of Acetylcholinesterase and Oxidative Stress.

Alzheimer's disease (AD) is a progressive neurological disorder characterized by loss of memory and cognition. Stephania japonica is being used as traditional medicine in the treatment of different neurological problems. In this study, we evaluated the anticholinesterase and antioxidant activities of the crude methanol extract of S. japonica and its fractions in vitro and the neuroprotective effect of the most active fraction in the scopolamine-induced mouse model of memory impairment. Among the crude extract and its fractions, chloroform fraction exerted strong inhibition of acetylcholinesterase and butyrylcholinesterase enzymes with IC50 values of 40.06 and 18.78 µg/mL, respectively. Similarly, the chloroform fraction exhibited potent antioxidant activity and effectively inhibited the peroxidation of brain lipid in vitro. The phytochemical profile revealed the high content of polyphenolics and alkaloids in the chloroform fraction. Pearson's correlation studies showed a significant association of anticholinesterase and antioxidant activity with alkaloid and phenolic contents. Kinetic analysis showed that the chloroform fraction exhibited a noncompetitive type of inhibition. In experimental mice, the chloroform fraction restored the impaired learning and memory induced by scopolamine as evidenced by a significant decrease in latency time and increase of quadrant time in probe trial in Morris water maze task. The chloroform fraction also significantly reduced the activity of acetylcholinesterase and oxidative stress in mice. Our results suggest that the chloroform fraction of S. japonica may represent a potential candidate for the prevention and treatment of AD.

A Mixture of Ginkgo biloba L. Leaf and Hericium erinaceus (Bull.) Pers. Fruit Extract Attenuates Scopolamine-Induced Memory Impairments in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by loss of memory and cognitive impairment via dysfunction of the cholinergic nervous system. In cholinergic dysfunction, it is well known that impaired cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling are major pathological markers and are some of the strategies for the development of AD therapy. Therefore, this study is aimed at evaluating whether a mixture comprising Ginkgo biloba L. leaf (GL) and Hericium erinaceus (Bull.) Pers. (HE) fruit extract (GH mixture) alleviated cognitive impairment induced in a scopolamine-induced model. It was discovered that GH reduced neuronal apoptosis and promoted neuronal survival by activating BDNF signaling in an in vitro assay. In addition, the GH (p.o. 240 mg/kg) oral administration group significantly restored the cognitive deficits of the scopolamine-induced mouse group (i.p. 1.2 mg/kg) in the behavior tests such as Y-maze and novel object recognition task (NORT) tests. This mixture also considerably enhanced cholinergic system function in the mouse brain. Furthermore, GH markedly upregulated the expressed levels of extracellular signal-regulated kinase (ERK), CREB, and BDNF protein levels. These results demonstrated that GH strongly exerted a neuroprotective effect on the scopolamine-induced mouse model, suggesting that an optimized mixture of GL and HE could be used as a good material for developing functional foods to aid in the prevention of neurodegenerative diseases, including AD.

Anti-amnesic effects of withaferin A, a steroidal lactone isolated from Withania adpressa, on scopolamine-induced memory impairment in mice

Natural secondary metabolites have long served as sources of drugs against various health disorders, among them neurodegenerative diseases especially Alzheimer’s disease (AD). Withanolides, isolated from Withania species , have shown acetylcholinesterase inhibition activity and their neuroprotective effects may be beneficial in the treatment of cholinergic system associated diseases, such as AD. This study was undertaken to highlight the neuroprotective effects of withaferin A (WA), isolated from W. adpressa leaves, using a scopolamine-induced memory impairment model in mice. The in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition potentials of WA were assessed. The learning and memory enhancing activities of WA at different doses (1, 3 and 5 mg/kg) were investigated utilizing Novel Object Recognition (NOR) and Barnes maze (BM). WA substantially inhibited AChE and BuChE enzymes with IC 50 values of 45.5 ± 0.14 and 68.2 ± 0.27 µg/mL, respectively. Noteworthy, rotarod results revealed no significant differences between WA and control groups. Also, learning, and spatial memory performance in NOR and BM tests were improved compared to the control groups. Furthermore, the activity of acetylcholinesterase in the brain was significantly inhibited ( p < 0.05) by WA at the three tested doses. WA possessed certain affinity in both enzymes with low binding energy compared to the reference drug donepezil in a molecular docking study. This study displays that WA could be used for enhancing learning and memory impairment and appears to be a promising candidate for Alzheimer’s disease treatment.

Sea Cucumber Peptides Attenuated the Scopolamine-Induced Memory Impairment in Mice and Rats and the Underlying Mechanism

Social stress and unhealthy diets lead to memory impairment, triggering health problems. This study aimed to determine the mitigating effect and regulation mechanism of sea cucumber peptides (SCP) against memory impairment. Here, scopolamine-induced memory impairment in mouse and rat models was used based on behavioral tests, a histological staining technique, Fourier transform infrared microscopy, and gas-chromatographic analysis as well as a Western blotting method. SCP improved the behavioral performance and regulated the disorder of the cholinergic system in mouse models in a dose-dependent manner. Therefore, the underlying mechanism was explored in high-dose SCP using mouse and rat models. SCP repaired damaged neuronal cells, enhanced the Nissl body number, increased the unsaturated lipid level, and activated the long-term potentiation (LTP) pathway (p-CaMKII, p-CREB, and BDNF), both in the mouse and rat hippocampus. The results indicated that SCP upregulated the LTP pathway and unsaturated lipid level to combat scopolamine-induced memory impairment, suggesting that SCP was a potential candidate for neurological recovery.

Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ1-42 aggregation effectively ranged from 45.9-94.5 % at 20 μM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self-induced Aβ1-42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

Phenolic Profiling and Therapeutic Potential of Certain Isolated Compounds from Parkia roxburghii against AChE Activity as well as GABAA α5, GSK-3β, and p38α MAP-Kinase Genes.

Parkia roxburghii belongs to the family Mimosaceae; it has been used since ancient times as a cure for different health complications; such as inflammatory and gynecological diseases and hemiplegia. In this investigation, a reversed-phase-high-performance liquid chromatography (RP-HPLC) profile was carried out for P. roxburghii; also, the isolated bioactive compounds including quercetin, catechin, and biochaninA were individually and/or in combination investigated for their inhibitory effects on scopolamine-induced memory impairments in mice, implying that they have the ability to reduce the neurodegenerative effects of scopolamine and thus could be employed as a more effective therapeutic agent in the treatment of Alzheimer’s disease (AD) in humans. The possible interactions of Parkia flavonoids with acetylcholinesterase (AChE), γ-aminobutyric acid A receptor, alpha5 (GABAA α5), glycogen synthase kinase-3 (GSK-3), p38 mitogen-activated protein kinase (p38MAP-kinase), signal-regulated kinase (ERK), and protein-serine/threonine kinase (Akt) were then determined using molecular docking.