Scopolamine-induced Amnesia Research Articles

Biological Evaluation of Cucumis trigonus (Roxb.) for Memory Enhancing Activity in Scopolamine-induced Amnesia in Mice

Introduction: Plants have been employed for centuries to enhance human health due to their cost-effectiveness and minimal adverse effects. Numerous plants exhibit a wide spectrum of pharmacological activities, and various herbal medicines are currently being investigated for their memory-enhancing properties. Method: Cucumis trigonus (Roxb.), commonly known as Kachari or Bitter gourd, is one such plant with diverse pharmacological attributes. Historically, the fruits of C. trigonus have been utilized for addressing various conditions like leprosy, pyrexia, icterus, hyperglycemia, chronic cough, bronchitis, abdominal fluid accumulation, anemia, obstipation, diverse gastrointestinal disease, and cognitive impairment. The current investigation aims to explore the memory enhancement properties of C. trigonus, rooted in its traditional applications, particularly against scopolamine-induced amnesia in mice. Morris water maze and elevated plus maze paradigms were employed to evaluate cognitive performance. Furthermore, the research examined acetylcholine neurotransmission, oxidative stress markers, and cerebral histopathology. Result: The results showed that C. trigonus ethanol extract (dose- 150 or 300 mg/kg., p.o.), markedly (p<0.05) improved memory in scopolamine-induced amnesia in mice and significantly (p<0.05) elevated hippocampus acetylcholine concentration. These findings revealed that the ethanol extract of C. trigonus fruits mitigates memory deficits and demonstrates neuroprotective efficacy analogous to the reference drug Piracetam. Additionally, the extract showed notable in vivo antioxidant activity. The occurrence of flavonoids and phenols is likely to be responsible for its memory-enhancing effects due to their antioxidant properties, which help to prevent the loss of neurons. Conclusion: These results support the efficacy and potential of C. trigonus ethanol extract as an affordable alternative form of herbal medicine for the treatment of Amnesia.

Analysis of Differential microRNA Expression in the Hippocampus of Scopolamine-Induced Amnesic Mouse Model.

Amnesia is characterized by memory deficits linked to various neurodegenerative pathologies and can be induced by the administration of scopolamine, a cholinergic antagonist. Scopolamine-induced amnesia is a well-studied pharmacological animal model that simulates memory impairment caused by aging, brain illnesses, neuropathologies, and trauma. However, the molecular mechanism of amnesia, more importantly in terms of microRNA (miRNA) regulation, is not well understood. Therefore, this study aimed to analyze miRNA profiles in the hippocampus of both control mice and those treated with scopolamine (amnesic mice). Initially, a short cDNA library was prepared for each sample and then sequenced on the Illumina platform. Among the total differentially expressed miRNAs, 113 were significantly upregulated and 96 were downregulated in the scopolamine group in comparison to the control group. Ten upregulated and ten downregulated miRNAs were validated to confirm the reliability of the sequencing results using qRT-PCR (quantitative real-time PCR). Furthermore, we performed a target prediction analysis intersecting the results from TargetScan, miRDB (miRNA database), and Miranda to analyze the targets of the dysregulated miRNAs. We also conducted a pathway analysis to investigate the molecular, cellular, and biological functions of these targets. miRNA‒target interactions were found to play roles in various signaling pathways during amnesia. These results provide an initial insight for the contribution of miRNAs to scopolamine-induced amnesia, as well as their possible application as markers of disease pathology.

Tat-Beclin-1 Ameliorates Memory by Improving Neuronal Cytoarchitecture and Mitigating Mitochondrial Dysfunction in Scopolamine-Induced Amnesic Male Mice.

Mitophagy, the targeted breakdown of damaged mitochondria, plays a vital role in maintaining cellular homeostasis. As impairment of mitophagy leads to neurodegeneration and memory decline, the current study explores the therapeutic potential of an autophagy inducer Tat-Beclin-1 during scopolamine-induced amnesia. Tat-Beclin-1 improved contextual and recognition memory and also mitochondrial ultrastructure by restoring mitochondrial length and area and reducing the number of fragmented mitochondria. Tat-Beclin-1 upregulated the expression of genes associated with mitophagy (PTEN-induced kinase 1, Parkin, Lamp2, and LC3), mitochondrial fusion (Mfn1, Mfn2, and optic atrophy1), and fission (dynamin-related protein 1 and Fis1) in amnesic mice. Subsequently, these results were supported by a decreased level of p-Drp1 (S616) and Drp 1 ratios and an increased level of Mfn2, LC3BI, and BII in Tat-Beclin-1-treated mice. Moreover, Tat-Beclin-1 maintained mitochondrial membrane potential and complex I/V activity in amnesic mice. Tat-Beclin-1 enhanced myelination and diminished the activity of acetylcholinesterase and caspase-3 activity. Sholl analysis revealed augmented dendritic branching and length, elevated dendritic spine density, and upregulated the expression of synaptophysin and PSD95 proteins, indicating neuronal plasticity enhancement by Tat-Beclin-1. Thus, these findings provide valuable insights into the therapeutic potential of Tat-Beclin-1, addressing mitochondrial dysfunction to mitigate cognitive impairment associated with amnesic conditions.

Berberine and Berberine Nanoparticles Mitigate Scopolamine-Induced Amnesia in Rats

Abstract Introduction/Objective Berberine (BER) has garnered attention in research for its multifaceted biochemical and pharmacological properties, positioning it as a promising natural remedy. Conversely, scopolamine (SCO) functions as a non-selective muscarinic receptor antagonist, disrupting central cholinergic neurotransmission and impairing learning and short-term memory. Methods/Case Report Forty-two male Wistar rats were procured from the National Research Center in Cairo, Egypt, and allocated randomly into seven groups, each comprising six rats. The groups were as follows: Sham Control (no treatment), BSA Control (received oral administration of 1 ml Bovine Serum Albumin-NP solution daily for 28 days), BRB-NP Control (received oral administration of BRB-NP nanoparticles at 5 mg/kg/day for 28 days), Induced Group (intraperitoneal injection of SCO at 2 mg/kg dissolved in saline once daily for 28 days), BER Treated Group (received BER at 50 mg/kg suspended in saline followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days), BSA Treated Group (received oral administration of 1 ml BSA-NP solution followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days), and BER-NP Treated Group (received oral administration of BER-NP at 5 mg/kg followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days). Whole blood was collected via heart puncture, and brain tissue was promptly extracted for brain homogenate preparation. Routine biochemical assays were conducted on serum and brain samples. Results (if a Case Study enter NA) Statistically significant differences were observed among the seven experimental rat groups concerning plasma AST, albumin, total protein, and triglyceride levels, while differences in ALT and total cholesterol were non-significant. Regarding brain parameters, significant differences were noted among groups in total protein, cholesterol, phospholipids, and uric acid levels. Conclusion Treatment with BRB NPs or free berberine led to a progressive increase in brain protein levels and a decrease in cholesterol content (p<0.05). Additionally, SCO administration resulted in a gradual reduction in brain phospholipid content, while treatment with BER NPs, regardless of the rat’s condition, exhibited the highest phospholipid levels (p<0.05). Furthermore, administration of BSA or free BRB improved brain uric acid levels (p<0.05).

Neuropharmacological Assessment of Sulfonamide Derivatives of Para-Aminobenzoic Acid through In Vivo and In Silico Approaches

Background/Objectives: Alzheimer’s disease (AD), a complex neurogenerative disorder, manifests as dementia and concomitant neuropsychiatric symptoms, including apathy, depression, and circadian disruption. The pathology involves a profound degeneration of the hippocampus and cerebral cortex, leading to the impairment of both short-term and long-term memory. The cholinergic hypothesis is among the various theories proposed, that assume the loss of the cholinergic tract contributes to the onset of AD and proves clinically effective in managing mild to moderate stages of the disease. This study explores the potential therapeutic efficacy of sulfonamide-based butyrylcholinesterase inhibitors in mitigating scopolamine-induced amnesia in rats. Methods: Behavioral assessments utilizing Y-maze, Barnes maze, and neurochemical assays were conducted to evaluate the effectiveness of the test compounds. Results: Results demonstrated a significant reduction in the impact of scopolamine administration on behavioral tasks at a dose of 20 mg/kg for both compounds. Correspondingly, neurochemical assays corroborated these findings. In silico docking analysis on rat butyrylcholinesterase (BChE) was performed to elucidate the binding mode of the compounds. Subsequent molecular dynamics studies unveiled the formation of stable complexes between the test compounds and rat BChE. Conclusions: These findings contribute valuable insights into the potential therapeutic role of sulfonamide-based butyrylcholinesterase inhibitors in addressing memory deficits associated with AD, emphasizing their in silico molecular interactions and stability.

Rhoifolin, baicalein 5,6-dimethyl ether and agathisflavone prevent amnesia induced in scopolamine zebrafish (Danio rerio) model by increasing the mRNA expression of bdnf, npy, egr-1, nfr2α, and creb1 genes

The increasing attention towards age-related diseases has generated significant interest in the concept of cognitive dysfunction associated with Alzheimer's disease (AD). Certain limitations are associated with the current therapies, and flavonoids have been reported to exhibit multiple biological activities and anti-AD effects in several AD models owing to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties. In this study, we performed an initial in silico predictions of the pharmacokinetic properties of three flavonoids (rhoifolin, baicalein 5,6-dimethyl ether and agathisflavone). Subsequently, we evaluated the antiamnesic and antioxidant potential of flavonoids in concentrations of 1, 3, and 5 μg/L in scopolamine (100 μM)-induced amnesic zebrafish (Danio rerio) model. Zebrafish behavior was analyzed by novel tank diving test (NTT), Y-maze, and novel object recognition test (NOR). Acetylcholinesterase (AChE) activity, brain antioxidant status and the expression of bdnf, npy, egr1, nrf2α, creb1 genes, and CREB-1 protein level was measured to elucidate the underlying mechanism of action. Our flavonoids improved memory and decreased anxiety-like behavior of scopolamine-induced amnesia in zebrafish. Also, the studied flavonoids reduced AChE activity and brain oxidative stress and upregulated the gene expression, collectively contributing to neuroprotective properties. The results of our study add new perspectives on the properties of flavonoids to regulate the evolution of neurodegenerative diseases, especially AD, by modulating the expression of genes involved in the regulation of synaptic plasticity, axonal growth, and guidance, sympathetic and vagal transmission, the antioxidant response and cell proliferation and growth.

In vivo neuroprotective effect of Guaiacum officinale leaf extracts in scopolamine-induced cognitive impairment model

ABSTRACT The phytochemical composition and neuroprotective potential of the ethanolic extract of Guaiacum officinale leaves against scopolamine-induced amnesia were investigated. Spatial memory was evaluated through the Morris water maze, while the entire brain was assessed for acetylcholinesterase (AchE), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The presence of glycosides, alkaloids, steroids, terpenoids, flavonoids, and saponins was detected in the ethanolic extract through phycological analysis. The findings suggested that the ethanolic extract alleviated scopolamine-induced spatial memory impairments caused by scopolamine and decreased the AchE activity. The study also detailed MDA, SOD, transfer latency periods, and acetylcholine esterase levels in both normal and extract-treated groups.

Anxiolytic and Antidepressant Effects of Tribulus terrestris Ethanolic Extract in Scopolamine-Induced Amnesia in Zebrafish: Supported by Molecular Docking Investigation Targeting Monoamine Oxidase A.

Plants of the genus Tribulus have been used in folk medicine for wound healing, alleviating liver, stomach, and rheumatism pains, and as cognitive enhancers, sedatives, antiseptics, tonics, and stimulants. The present work aimed to evaluate whether Tribulus terrestris (Tt) administered for 15 days attenuated cognitive deficits and exhibited anxiolytic and antidepressant profiles in scopolamine-induced amnesia in zebrafish. Animals were randomly divided into six groups (eight animals per group): (1)-(3) Tt treatment groups (1, 3 and 6 mg/L), (4) control, (5) scopolamine (SCOP, 0.7 mg/kg), and (6) galantamine (Gal, 1 mg/L). Exposure to SCOP (100 µM) resulted in anxiety in zebrafish, as assessed by the novel tank diving test (NTT) and novel approach test (NAT). When zebrafish were given SCOP and simultaneously given Tt (1, 3, and 6 mg/L once daily for 10 days), the deficits were averted. Molecular interactions of chemical compounds from the Tt fractions with the monoamine oxidase A (MAO-A) were investigated via molecular docking experiments. Using behavioral experiments, we showed that administration of Tt induces significant anxiolytic-antidepressant-like effects in SCOP-treated zebrafish. Our result indicated that flavonoids of Tt, namely kaempferol, quercetin, luteolin, apigetrin, and epigallocatechin, could act as promising phytopharmaceuticals for improving anxiety-related disorders.

Discovery and structure − activity relationships of 2,4,5-trimethoxyphenyl pyrimidine derivatives as selective D5 receptor partial agonists

Dopamine receptors are therapeutic targets for the treatment of various neurological and psychiatric disorders, including Parkinson’s and Alzheimer’s. Previously, PF-06649751 (tavapadon), PF-2562 and PW0464 have been discovered as potent and selective G protein-biased D1/D5 receptor agonists with optimal pharmacokinetic properties. However, no selective D5R agonist has been reported yet. In this context, we designed and synthesized forty non-catecholamines-based pyrimidine derivatives and identified four pyrimidine derivatives as selective D5R partial agonists. Using cAMP-based GloSensor assay in transiently transfected HEK293T cells with human D1 or D5 receptors, we discovered that compound 5c (4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine) exhibited modest D5R agonist activity. This leads us to explore various modifications of this scaffold to improve the D5 agonist potency and efficacy. Using molecular docking, and rational design followed by their evaluation at D1 and D5 receptors for agonist activity, we identified three new derivatives, 5j, 5h, and 5e. The most potent compound of this series 5j (4-(4-iodophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-amine), exhibited EC50 of 269.7 ± 6.6 nM. Mice microsomal stability studies revealed that 5j is quite stable (>70 % at 1 hr). Furthermore, pharmacokinetic analysis of 5j (20 mg/kg, p.o) in C57BL/6j mice showed that 5j is readily absorbed via oral route of dosing and also enters into the brain (plasma Tmax: 1 h, Cmax: 51.10 ± 13.51 ng/ml; Brain Tmax: 0.5 h, Cmax: 22.54 ± 4.08 ng/ml). We further determined the in-vivo effect of 5j on cognition in scopolamine-induced amnesia in C57BL/6j mice. We observed that 5j (10 mg/kg, p.o) alleviated scopolamine-induced impairment in short-term memory and social recognition, which were blocked by D1/D5 antagonist SCH23390 (0.1 mg/kg, i.p.). Furthermore, 5j did not exhibit any cytotoxicity (up to 10 µM) or in vivo acute toxicity up to 200 mg/kg (p.o). These results strongly suggest that 5j could be further developed for treating neurological disorders wherein the D5 receptors play pivotal roles.

Ameliorative potential of ethanol extract of Calyptrochilum emarginatum leaves on scopolamine-induced amnesia in male swiss mice

Ethnopharmacological relevanceCalyptrochilum emarginatum (Afzel. Ex Sw.) Schltr. (Orchidaceae) is a traditional medicinal plant known for its antimicrobial properties and efficacy in managing convulsive fever and menstrual disorders and addressing conditions such as malaria, tuberculosis, and cough. Aim of the studyThe study aims to examine the memory-enhancing and neuroprotective properties of ethanol extract of Calyptrochilum emarginatum leaves (EECEL) in scopolamine-induced amnesia mice model. Materials and methodsForty-two male mice were divided into six groups (n = 7). Group 1 served as control, administered distilled water (10 mL/kg, p. o), group 2 received scopolamine only (3 mg/kg, i. p.), groups 3 to 6 received pretreatments of EECEL (50, 100, and 200 mg/kg, p. o.) and donepezil (1 mg/kg, p. o.) 30 min before scopolamine (3 mg/kg), for seven days. Following treatments, behavioral (learning and memory) assessments were carried out, while biochemical (acetylcholinesterase activity, oxidative stress markers, inflammatory cytokines markers) and histological evaluations were done after euthanasia. ResultsScopolamine significantly impaired spatial, long term and recognition memory. Nevertheless, administration of EECEL (50, 100, and 200 mg/kg orally) enhanced memory function in mice, as observed in the Y maze [F (5, 30) = 20.23, p < 0.0001], Morris water maze [F (10, 90) = 3.105, p = 0.0019; [F (5, 30) = 21.13, p < 0.0001]], and novel object recognition tasks [F (5, 30) = 37.22, p < 0.0001)]. Scopolamine-treated mice exhibited significant dysfunction in the cholinergic system, as evidenced by elevated AChE activity [0.099 ± 0.005 vs. 0.063 ± 0.004 mol/min/g] with an elevation in oxidative stress. On the other hand, administration of EECEL counteracted these consequences by reducing AChE activity, mitigating oxidative damage, reducing pro-inflammatory cytokines, and preventing degeneration of neurons. ConclusionThe results demonstrated that EECEL effectively mitigates scopolamine-induced memory impairment via an oxido-inflammatory mechanism and modulation of the central cholinergic system.

Moderate capsaicin-containing kochujang alleviates memory impairment through the gut-brain axis in rats with scopolamine-induced amnesia

This study investigated the efficacy and mechanism of traditionally made kochujang(TMK) with different capsaicin levels to alleviate memory impairment in rats with scopolamine-induced amnesia. Sprague-Dawley male rats were administered scopolamine (2 mg/kg bw/day) intraperitoneally to suppress the parasympathetic nervous system(PNS) and induce memory impairment. The rats were divided into four experimental groups, each consuming a diet containing 1 % kochujang in a 43-energy% high-fat diet(HFD) for 8 weeks. The TMK samples used for the study were categorized according to their capsaicin(CPS) content as follows: Low-CPS(0.5 mg%), medium-CPS(1.2 mg%), and high-CPS(1.7 mg%). In addition, factory-made kochujang (FMK; 1.1 mg% capsaicin) was also tested. The effects of kochujang were compared with the Control group(scopolamine), Positive-control(scopolamine+donepezil), and Normal-control(saline) fed HFD. Kochujang consumption reduced body weight and fat mass compared to the Control group. Compared to the Control, memory function measured using passive avoidance, water maze, and novel object recognition tests was enhanced in kochujang-fed rats, especially in the Medium-CPS group, similar to Positive-control. The Medium-CPS and Positive-control groups also exhibited inhibition of hippocampal cell death and increased cholesterol and triglyceride contents and mRNA expression of TNF-α and IL-1β in the brain tissue compared to the Control group. Additionally, TMK elevated short-chain fatty acid, particularly, butyrate concentration in the portal vein. Scopolamine disturbed large intestine cell morphology and gut microbiota composition, and kochujang improved them. Kochujang in the medium-CPS (1.2 mg%) had a more significant impact on the gut microbiota in the interaction analysis between gut microbiota and memory function. In conclusion, kochujang, especially with medium-CPS (1.2 mg%), is a potential dietary intervention to mitigate memory impairment and promote overall cognitive health through improving eubiosis, potentially linked to the gut-brain axis in PNS-suppressed rats.

Neuroprotective Effect of Ashtanga Ghrita on Spatial Learning and Memory in Scopolamine-Induced Amnesia in Rat Model

Neuroprotective Effect of Ashtanga Ghrita on Spatial Learning and Memory in Scopolamine-Induced Amnesia in Rat Model

Ethanolic extract of Actinidia chinensis var. delicious fruit ameliorates scopolamine-induced cognitive impairment in rats

AimThe present study was to assess the anti-amnesic effect of Actinidia chinensis var deliciosa in a rat model of scopolamine-induced amnesia. Method36 rats were divided into 6 groups and assigned name to each group i.e. Group 1 rats (normal control) received 1 ml/kg normal saline for 14 days intraperitoneally (i.p.). Group 2 rats received scopolamine (3 mg/kg, i.p.) 30 min prior to the trial on the 14th day. Group 3 rats received 3 mg/kg/day of donepezil as pre-treatment for 14 days and scopolamine (3 mg/kg, i.p.) 30 min before the trial on the 14th day. Group 4, 5, and 6 rats received Actinidia chinensis var deliciosa (200, 400, and 600 mg/kg/day) for 14 days and scopolamine (3 mg/kg, i.p) 30 min before the trial on the 14th day respectively. On day 15, 6 rats from each group were sacrificed and the brain tissue of these rats was isolated for the estimation of biochemical parameters, and histopathological examination. ResultScopolamine-treated rats demonstrated increased escape latency and lipid peroxidation levels in the hippocampus compared to the control group (p < 0.001). However, pre-treatment with Actinidia chinensis var deliciosa extract (ACEE) at various doses and the standard drug donepezil significantly improved these parameters. Histopathological examination revealed that ACEE and donepezil protected against pyramidal cell degeneration, neuronophagia, and vascular inflammation in scopolamine-treated rats. Discussion: Actinidia chinensis var deliciosa showed promising anti-amnesic activity against scopolamine-induced amnesia in rats. This could be attributed to its brain acetylcholinesterase level and alteration in neurotransmitter level.

Evaluation of nootropic and neuroprotective properties of Siddha drug Poorana Chandrothaya Chenthuram (PCC) in scopolamine-induced amnesia in mice

BackgroundPoorana Chandrothaya Chenthuram (PCC) is a gold-based Siddha drug, for treating diverse diseases. Rooted in centuries-old traditional use, Siddha texts categorize PCC as a kayakarpa entity that emphasizes holistic well-being. AimThis study assesses the nootropic potential of Poorana Chandrothaya Chenthuram (PCC) in scopolamine-induced amnesic mice, and elucidate the underlying mechanisms, specifically focusing on the modulation of cholinergic system and anti-oxidant effects. MethodsPreliminary finger printing with FTIR was done. Scopolamine-induced memory impaired mice were administered PCC (15 or 30 mg/kg) for 28 days. Memory assessments were done using elevated plus-maze and passive avoidance tasks. RT-PCR gauged mRNA expression levels of AChE, MChR, BAX, and BCL2 in brain samples were also done. ResultsFTIR confirmed the presence of functional groups in PCC. In the EPM test, pre-treatment with PCC (15 and 30 mg/kg) significantly reduced the time taken (p < 0.05 and 0.01, respectively), comparable to the reference control, piracetam. The PAT revealed a significant increase (p < 0.01) in the time taken to step down from the escape platform which demonstrates that significant efficacy in reversing scopolamine-induced amnesia in mice. Gene expression studies reported a significant up-regulation (p < 0.01) in AChE, MChR, and BAX mRNA expressions, along with a down-regulation in BCL2 expression compared to normal mice. ConclusionThis study demonstrates the anti-amnesic activity of the Siddha drug PCC, elucidating its mechanism involving a reduction in AChE levels and an augmentation of antioxidant levels in which implicates modulation of cholinergic and apoptotic pathways. In-depth exploration of PCC's neuroprotective properties may unveil novel avenues for combating memory and cognitive decline.

Evaluation of the Therapeutical Effect of Matricaria Chamomilla Extract vs. Galantamine on Animal Model Memory and Behavior Using 18F-FDG PET/MRI.

The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic profile determined by an enriched MCE has not been performed before. The present experiments compared metabolic quantification in characteristic cerebral regions and behavioral characteristics for normal, only diseased, diseased, and MCE- vs. Galantamine (Gal)-treated Wistar rats. A memory deficit was induced by four weeks of daily intraperitoneal Sco injection. Starting on the eighth day, the treatment was intraperitoneally administered 30 min after Sco injection for a period of three weeks. The memory assessment comprised three maze tests. Glucose metabolism was quantified after the 18F-FDG PET examination. The right amygdala, piriform, and entorhinal cortex showed the highest differential radiopharmaceutical uptake of the 50 regions analyzed. Rats treated with MCE show metabolic similarity with normal rats, while the Gal-treated group shows features closer to the diseased group. Behavioral assessments evidenced a less anxious status and a better locomotor activity manifested by the MCE-treated group compared to the Gal-treated group. These findings prove evident metabolic ameliorative qualities of MCE over Gal classic treatment, suggesting that the extract could be a potent neuropharmacological agent against amnesia.

Appraisal of the Neuroprotective Potentials of Isoeugenol Using In-vitro, In-vivo and In-silico Approaches

Appraisal of the Neuroprotective Potentials of Isoeugenol Using In-vitro, In-vivo and In-silico Approaches

Exploring the neuropharmacological potential of empagliflozin on nootropic and scopolamine-induced amnesic model of Alzheimer’s like conditions in rats

Background Alzheimer’s disease (AD) is one of the most challenging and prevalent neurodegenerative disorder globally with a rising prevalence, characterized by progressive cognitive decline, memory loss, and behavioural changes. Current research aims to determine the nootropic and anti-amnesic effect of Empagliflozin (EMPA) against scopolamine-induced amnesia in rats, by modulating the cholinergic and N-Methyl D-Aspartate (NMDA) receptors. Methods Rats were treated once daily with an EMPA (5 and 10 mg/kg) and donepezil (2.5 mg/kg) for successive 26 days. During the final 13 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. Results EMPA was found to be significantly reduce escape latency, increase time spent in the target quadrant, and enhanced the number of target zone crossings in the Morris water maze (MWM) test, indicating improved spatial memory. Moreover, EMPA increased the recognition index and the number of spontaneous alternations in the novel object recognition (NOR) and Y-maze tests, respectively, suggesting enhanced memory. Discussion Interestingly doses of EMPA (5 mg/kg, 10 mg/kg) exhibited memory-enhancing effects even in the absence of scopolamine-induced impairment. Biochemical analysis revealed that EMPA elevated the levels of glutathione (GSH), a potent antioxidant, while decreasing lipid peroxidation (LPO) activity and increasing catalase (CAT) levels, indicating its antioxidative properties. Interestingly molecular docking studies revealed that EMPA fit perfectly in the active sites of M1 muscarinic acetylcholine (mACh) and NMDA receptors. These results indicated that the nootropic and antiamnesic effect of EMPA is possibly mediated via M1 and NMDA receptors and might be a remedy for AD.

Manasamitra Vatakam on Scopolamine-Induced Amnesia in Female Wistar Rats

ABSTRACT Background: Neurodegenerative diseases induce amnesia, and effective treatment is still elusive. Aims and Objectives: The present study highlights the ameliorating effects of Manasa Mitra Vatakam (MMV) using behavioral parameters on scopolamine-induced memory loss in female Wistar rats. Materials and Methods: MMV was compared with DPZ as a standard in the present study to determine the behavioral parameters through elevated plus maze (Hebb William maze/rectangular maze)and locomotor activity in scopolamine-induced memory loss in female Wistar rats. Results and Discussion: The results of the study illustrate the effectiveness of MMV in reversing memory dysfunction and memory-enhancing effects. Conclusion: The study paves the way for exploring research in CNS disorders and its potential application in drug-induced neurotoxicity.

Coal-Derived Humic Substances: Insight into Chemical Structure Parameters and Biomedical Properties.

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.

Dihydroergotamine Increases Histamine Brain Levels and Improves Memory in a Scopolamine-Induced Amnesia Model.

The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.