Administration Of Scopolamine Research Articles

A comprehensive analysis of in-hospital adverse events after scopolamine administration: insights from a retrospective cohort study using a large nationwide inpatient database

BackgroundScopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.MethodsA large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to examine the impact of perioperative scopolamine use on in-hospital adverse events. Patients were divided into age groups and compared to a control group. The primary outcomes assessed were delirium, pneumonia, in-hospital death, new antipsychotic use, readmission, and new onset urinary retention within 7 days post-surgery. 1:1 propensity score matching was performed to reduce bias. Relative risk and risk differences with 95% confidence intervals were estimated.ResultsAfter 1:1 propensity score matching, we identified a total of 403,816 (201,908 pairs) perioperative scopolamine users and nonusers. The cohorts of 20–29, 30–39, 40–49, 50–59, 60–69, and 70 + contained 22,910 (11,455 pairs), 44,170 (22,085 pairs), 58,590 (29,295 pairs), 71,660 (35,830 pairs), 88,386 (44,193 pairs), and 118,100 (59,050 pairs) patients respectively. Across older age cohorts, after propensity score matching, perioperative scopolamine recipients had significantly increased relative risk and risk difference of delirium, pneumonia, in-hospital mortality, new antipsychotic use, readmission, and new-onset urinary retention.ConclusionsIn this cohort study, perioperative scopolamine usage was associated with a significantly increased risk of in-hospital adverse events, both within the 70 + age cohort and among the 20–29, 30–39, 40–49, 50–59, and 60–69 age cohorts after major surgery. These findings highlight the need for careful assessment of scopolamine’s risks and benefits, especially for patients aged 40 and older. Scopolamine may be most suited for post-discharge nausea and vomiting in ambulatory patients and clinicians should reassess its standard use for postoperative nausea and vomiting, favoring shorter-acting agents with fewer side effects.

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.

Ambroxol Improves Amyloidogenic, NF-κB, and Nrf2 Pathways in a Scopolamine-Induced Cognitive Impairment Rat Model of Alzheimer's Disease.

Ambroxol (ABX) is used to manage excessive production of mucus in the respiratory system. The present study sought to assess the neuroprotective potential of ambroxol by influencing the amyloidogenic, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways in a rat model of Alzheimer's disease (AD) induced by scopolamine. The AD pathology was induced by chronic administration of scopolamine. The rats were given scopolamine at a dose of 2 mg/kg via intraperitoneal injection daily for 14 days, followed by treatment (ABX 121.5, 135, and 180 mg/kg orally and 5 mg/kg orally of donepezil) for the next 28 days while continuing to receive daily scopolamine injection. The behavior of the rats was evaluated using Modified Y-Maze and Novel object recognition tasks. Analyses were carried out on AD pathological markers [Amyloid beta peptide 1-40, Amyloid beta peptide 1-42, acetylcholinesterase, beta-secretase 1 (BACE1), total tau, and p-tau], inflammatory markers [NF-κB, tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interferon γ], antioxidant markers (Nrf2 and heme Oxygenase 1 (HO-1)], along with synaptophysin and glial fibrillary acidic protein (GFAP) immunohistochemistry and histopathological assessment of the hippocampus. Our findings indicated that ABX reduced impairment in behavior. Levels of Acetylcholinesterase, BACE1, amyloid beta 1-40, amyloid beta 1-42, total tau, p-tau, NF-κB, IFN-γ, IL-6, and TNF-α decreased significantly. There was a significant increase in the levels of HO-1 and Nrf2. It stopped the neuronal degeneration, raised synaptophysin immunoreactivity, and lowered GFAP immunoreactivity. The current research indicates that ambroxol may possess senomorphic properties by impacting the transcription factors NF-κB and senescence-associated secretory phenotype (SASP). Consequently, it could provide neuroprotection through alterations in the Nrf2 and NF-κB signaling pathways in AD.

Comparison of Malondialdehyde, Acetylcholinesterase, and Apoptosis-Related Markers in the Cortex and Hippocampus of Cognitively Dysfunctional Mice Induced by Scopolamine.

Objectives: Until now, many researchers have conducted evaluations on hippocampi for analyses of cognitive dysfunction models using scopolamine. However, depending on the purposes of these analyses, there are differences in the experimental results for the hippocampi and cortexes. Therefore, this study intends to compare various analyses of cognitive dysfunction after scopolamine administration with each other in hippocampi and cortexes. Methods: Scopolamine was administered at three dosages in mice: 0.5, 1, and 3 mg/kg. And this study evaluates the differences in cognitive function and the expression of malondialdehyde (MDA), acetylcholinesterase (AChE), and brain-derived neurotrophic factor (BDNF) in mice's hippocampi and cortexes based on scopolamine dosages. Results: The Morris water maze test was conducted between 1 and 3 h after scopolamine injection to assess its duration. A significant decrease in behavioral ability was evaluated at 1 h, and we observed a similar recovery to the normal group at 3 h. And the Morris water maze escape latency showed differences depending on scopolamine concentration. While the escape waiting time in the control group and scop 0.5 administration group remained similar to that seen before administration, the administration of scop 1 and 3 increased it. In the experimental group administered scop 1 and 3, cerebral MDA levels in the cerebral cortex significantly increased. In the hippocampus, the MDA level in the scopolamine-administered groups slightly increased compared to the cortex. A Western blotting assay shows that Bax and Bcl-xl showed a tendency to increase or decrease depending on the concentration, but BDNF increased in scop 0.5, and scop 1 and 3 did not show a significant decrease compared to the control at the cerebral cortex. In the hippocampus, BDNF showed a concentration-dependent decrease in expression. Conclusions: This study's findings indicate that chemical analyses for MDA and AChE can be performed in the cerebral cortex, while the hippocampus is better suited for protein analysis of apoptosis and BDNF.

Evaluating Antioxidant Enzyme Parameters in Rats Treated with Berberine-Loaded Bovine Serum Albumin Nanoparticles and Scopolamine

Abstract Introduction/Objective Introduction: Berberine (BER) has garnered attention for its antioxidant properties demonstrated in various studies, showing its ability to scavenge or inhibit reactive oxygen species (ROS) and reactive nitrogen species (RNS), including nitric oxide, superoxide anion, and peroxynitrites. Methods/Case Report Methods: Forty-two male Wistar rats were randomly assigned to seven groups, each comprising 6 rats: Sham control (no treatment), BSA-NPs orally administered, BRB-NPs orally administered, SCO intraperitoneally injected, BER followed by SCO injection, BSA-NPs with SCO injection, and BER-NPs with SCO injection. Treatments were administered daily for 28 days. The cholinergic status was evaluated by assessing acetylcholinesterase (AChE) activity in brain homogenates, and brain homogenate Aβ-42 levels were measured using the ELISA technique. Additionally, brain prooxidant markers (NO, TBARS, XO), nonenzymatic antioxidants (GSH), and enzymatic antioxidants (GPx, GST, and SOD) were measured. Results (if a Case Study enter NA) Results: The study revealed that treatment with BRB NPs resulted in the lowest AChE activity and Aβ-42 levels. Scopolamine administration significantly increased brain NO, TBARS, and XO activity, accompanied by a progressive depletion in GSH content (p<0.05). Treatment with BRB-free or BSA decreased NO levels, while the BSA or BRB-NPs groups exhibited higher brain TBARS levels than the sham group. All treated groups exhibited similar activity to the sham control, except for the BSA-treated group. Furthermore, all treated groups showed comparable GSH levels to the sham control, except for the scopolamine group. Treatment with BRB NPs normalized GPx activity and showed the highest GST activity. The BRB-NPs treated group also exhibited the highest SOD level. The p-value was <0.001 among all studied groups. Conclusion Conclusion: Injection of SCO induced oxidative impairments in brain tissue, evidenced by increased prooxidants such as NO and depletion of antioxidant capacity (GPx, GST, and GSH). SCO also disrupted glutathione metabolism, enhancing the level of lipid peroxidation in the brain. Treatment with BRB-NPs or free BRB progressively increased antioxidant capacity and mitigated the harmful effects of oxidative damage in the brain by reducing prooxidant levels.

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).

Protective effects of licofelone on scopolamine-induced spatial learning and memory impairment by enhancing parkin-dependent mitophagy and promotion of neural regeneration and in adult mice

Inhibition of COX and LOX could contribute to memory formation and prevention of neurodegeneration, by alleviation of neuroinflammation and improvement of mitochondrial homeostasis. We aimed to assess the effect of licofelone, a dual COX and 5-LOX inhibitor on memory formation, neural apoptosis, neural regeneration, and mitophagy in acute and chronic dosages, given that licofelone could regulate nitric oxide levels. Y-maze and Passive Avoidance tests were used to evaluate memory function in NMRI mice using the EthoVision setting, following scopolamine administration (1 mg/kg, i.p.) as an acute amnestic drug. Hippocampi were used to evaluate the levels of apoptosis via TUNEL assay, neural regeneration via immunohistochemistry method detecting doublecortin and nestin, and mitophagy via Western blot of mitophagy proteins Parkin and ATG5. While acute high-dose licofelone (20 mg/kg) could reverse amnestic effects of scopolamine in passive avoidance test (p = 0.0001), Chronic licofelone (10 mg/kg for 10 consecutive days) could improve performance in Y-maze (p = 0.0007). Molecular analysis revealed that the chronic form of the drug could enhance neural regeneration in CA1 and SGZ regions, reset mitophagy levels as much as the healthy state, and reduce apoptosis rate. Licofelone appears to show a desirable anti-amnestic profile in a low dose chronically; it is hence recommended for future clinical studies on the prevention of neuroinflammation and memory deficit.

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.

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.

Neuroprotective Effects of Dehydroepiandrosterone and Hericium erinaceus in Scopolamine-induced Alzheimer's Diseases-like Symptoms in Male Rats.

The neuroprotective effects of Dehydroepiandrosterone (DHEA) and Hericium erinaceus (H. erinaceus) mushroom extract against scopolamine-induced Alzheimer's disease-like symptoms in male Wistar rats were investigated. Sixty-four male Wistar rats were divided into eight groups (n = 8). Scopolamine (SCO) was intraperitoneally injected at a dose of 1 mg/kg/day for 10 days. The treatment groups orally received DHEA (250 mg/kg/day) and/or H. erinaceus (300 mg/kg/day) for 14 days. Afterward, the Morris water maze (MWM) and novel object recognition tests were implemented. Then, animals were anesthetized and the brain tissue samples were separated. Levels of lipid peroxidation (LPO), total antioxidant capacity (TAC), catalase activity (CAT), and brain-derived neurotrophic factor (BDNF) were determined. Also, histopathological studies were evaluated in the brain tissue samples. Administration of SCO significantly decreased spatial and cognitive memory (p < 0.001). Not only did SCO injection significantly increase the levels of the LPO but also the SCO markedly reduced the levels of the TAC, CAT activity, and the BDNF in the brain tissue. On the other hand, a combination of the DHEA and H. erinaceus showed higher efficacy than the DHEA or H. erinaceus in attenuating behavioral anomalies and improving the antioxidant defense system and BDNF levels. Histological examination was well correlated with biochemical findings regarding SCO neurodegeneration and DHEA and/or H. erinaceus neuroprotection. Interestingly, ADHE and/or H. erinaceus may due to their potential neurotrophic properties be used as a new and beneficial concurrent therapy in the treatment of Alzheimer's disease-like symptoms caused by SCO.

Neuroprotective effects of Paederia foetida Linn. on scopolamine-induced cognitive impairment in rats.

Alzheimer's disease (AD) poses a significant health-care challenge, often linked to cognitive decline caused by oxidative stress. This study investigated the potential neuroprotective effects of the Paederia foetida leaf extract (PFE) in rats that exhibited scopolamine-induced dementia mimicking AD. Forty-two male rats were treated with either donepezil (0.5 mg/kg) or PFE at doses of 250, 500, and 1000 mg/kg for 14 days before and 14 days after the beginning of Alzheimer's-like symptoms after 14 consecutive days of scopolamine administration. Behavioral tests, including the open-field test for locomotor activity and the Morris water maze task for learning and memory assessment, were conducted. Neuronal cell counts and biochemical assays were performed to further analyze outcomes. All groups exhibited normal locomotor activity. The scopolamine group displayed longer escape latency times, reduced time in the target quadrant, decreased number of surviving neurons, and increased malondialdehyde and decreased glutathione levels compared with the control group. However, pre-treatment with 1000 mg/kg PFE notably mitigated the neurotoxic effects of scopolamine. The neuroprotective properties of PFE are highlighted, suggesting its potential as a promising treatment strategy for AD.

Subchronic administration of scopolamine reverses UCMS-induced behavior in mice via eEF2 protein dephosphorylation

BackgroundThe cholinergic system has been increasingly linked to the pathophysiology of mood disorders such as depression, with the potential involvement of nicotinic and/or muscarinic receptors. Conventional antidepressants usually require weeks of daily dosing to achieve a full antidepressant response. In contrast, clinical studies have shown that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, can induce potent and rapid antidepressant effects, requiring only a few days of treatment. This study aimed to examine the suitability of the unpredictable chronic mild stress (UCMS) model of depression to reproduce the above scopolamine antidepressant activity patterns.MethodsRapid and sustained antidepressant-like effects were assessed by using the splash test, sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST) in animals undergoing the UCMS procedure and stress-naïve C57BL/6J mice. Western Blotting was used to measure tropomyosin receptor kinase B (TrkB), mammalian target of rapamycin (mTOR), eukaryotic elongation factor (eEF2) and postsynaptic density protein 95 (PSD95) levels.ResultsScopolamine induced antidepressant-like effects in a dose-dependent manner only after subchronic, but not single, administration in the UCMS model of depression in C57BL/6J mice without affecting locomotor activity. Specifically, scopolamine administered at a dose of 0.3 mg/kg for four consecutive days significantly reversed the UCMS-induced depressive-like behavior, such as apathy, anhedonia, and behavioral despair, while scopolamine, given at the same dose but only once, did not relieve the above symptoms. Scopolamine treatment was accompanied by eEF2 protein dephosphorylation and its subsequent reactivation in the prefrontal cortex (PFC).ConclusionSubchronic administration of scopolamine is needed to ameliorate UCMS-induced depressive-like behavior. The suggested mechanism of scopolamine action covers eEF2 protein activity in the PFC.

Memory enhancing and neuroprotective effects of apomorphine in a rat model of dementia.

Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1mg/kg could be a potential therapeutic agent to treat dementia and related disorders.

Ferulago Angulata methanolic extract ameliorates scopolamine-induced memory impairment through the inhibition of hippocampal monoamine oxidase activity.

Ferulago angulata is a medicinal herb from the Apiaceae family known for its antioxidant, anti-apoptotic, and neuroprotective properties. This study aimed to assess the effects of F. angulata extract on neurobehavioral and biochemical parameters in scopolamine-induced amnesic rats. Fifty-six male Wistar rats were divided into seven groups and orally treated with F. angulata extract (100, 200, 400mg/kg) and Rivastigmine (1.5mg/kg) for 10 days. Starting on the sixth day of treatment, the Morris water maze behavioral study was conducted to evaluate cognitive function, with scopolamine administered 30min before training. Biochemical assays, including monoamine oxidase and oxidative stress measures, were performed on hippocampal tissue. Results showed that extract treatment significantly attenuated scopolamine-induced memory impairment in a dose-dependent manner. Following scopolamine administration, malondialdehyde levels and monoamine oxidase A/B activity increased, while total thiol content and catalase activity decreased compared to the control group. Pretreatment with F. angulata extracts ameliorated the scopolamine-induced impairment in all factors. Toxicological evaluation of liver, lung, heart, and kidney tissues did not indicate any side effects at high doses. The total extract of F. angulata prevents scopolamine-induced learning and memory impairment through antioxidant mechanisms and inhibition of monoamine oxidase. These results suggest that F. angulata extract is effective in the scopolamine model and could be a promising agent for preventing dementia, especially Alzheimer's disease.

Neuroprotective properties of UV-C treated Bacopa floribunda leaves: in vitro and in vivo studies

This study investigated the effect of UV-C irradiation on antioxidant, cholinergic and neuroprotective properties of Bacopa floribunda leaves in scopolamine-induced rats. In vitro study was done by the determination of phenolics, flavonoid, total antioxidant capacity, 2, 2-diphenyl-1-picrylhydrazyl scavenging activity, inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Loss of memory was induced in Wistar rats pre-treated with extracts of Bacopa floribunda using scopolamine (2 mg/kg) administered intraperitoneally. Behavioural studies using elevated plus maze (EPM) and biochemical analysis on the were carried out. Exposure to UV-C radiation increased the phenolics, flavonoid, antioxidant and inhibitory properties against AChE and BChE of the Bacopa floribunda leaves. The administration of scopolamine caused significant increase in the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, but decrease in the activities of antioxidant enzymes and enhanced generation of malondialdehyde and nitric oxide in vivo. The loss of memory and Biochemical analysis in scopolamine-induced rats was ameliorated by treatment with UV-C treated Bacopa floribunda (TBF) extracts. Treatment with TBF improved memory retention and ameliorated oxidative damage in hippocampus of scopolamine treated rats.

The role of the cholinergic system in the memory-protecting effects of metformin in a model of scopolamine-induced memory impairment in aged rats

PurposeAs the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions. MethodsMetformin was administered orally to male Wistar rats (20–22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis. ResultsImpaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity. ConclusionOur results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect.

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.

Effects of extracts and manna of Echinops cephalotes on impaired cognitive function induced by scopolamine in mice.

Alzheimer's disease (AD) is a neurodegenerative disease specified by chronic and irreversible destruction of neurons. This study aimed to evaluate the effects of different extracts (aqueous, hydroalcoholic, hexane, and ethyl acetate) and manna of Echinops cephalotes (EC) on impaired cognitive function induced by scopolamine in mice. EC is shown to have anti-cholinesterase-butyrylcholinesterase activities. In this study, aqueous and hydroalcoholic extracts, hexane and ethyl acetate fractions of EC (25, 50, 100 mg/kg, i.p.), and the manna (25, 50, 100 mg/kg, gavage) were administered for 14 days alongside scopolamine (0.7 mg/kg, i.p.). Rivastigmine (reference drug) was administered for 2 weeks i.p. Mice were tested for their memory function using two behavioral models, object recognition test (ORT) and passive avoidance test (PAT). Administration of scopolamine significantly impaired memory function in both behavioral models. In the PAT model, all extracts at 50 and 100 mg/kg significantly reversed the effect of memory destruction caused by scopolamine. At a lower dose of 25 mg/kg, however, none of the extracts were able to significantly change the step-through latency time. In the ORT model, however, administration of all extracts at 50 and 100 mg/kg, significantly increased the recognition index. Only the manna and the aqueous extract at 25 mg/kg were able to reverse scopolamine-induced memory impairment. These results suggest that all forms of EC extracts improve memory impairment induced by scopolamine comparably to rivastigmine. Whether the effects are sustained over a longer period remains to be tested in future work.

The Effect of a Tribulus-Based Formulation in Alleviating Cholinergic System Impairment and Scopolamine-Induced Memory Loss in Zebrafish (Danio rerio): Insights from Molecular Docking and In Vitro/In Vivo Approaches.

Tribulus terrestris L. (Tt) has been recently gaining attention for its pharmacological value, including its neuroprotective activities. In this study, we explore the neuroprotective effects of a Tribulus terrestris extract in a zebrafish (Danio rerio) model of scopolamine (SCOP)-induced memory impairment and brain oxidative stress. SCOP, an anticholinergic drug, was employed to replicate fundamental aspects of Alzheimer's disease (AD) in animal models. The fish were treated with ethanolic leaf extract (ELE) from Tt (1, 3, and 6 mg/L) for 15 days. SCOP (100 µM) was administered 30 min before behavioral tests were conducted. Molecular interactions of the major compounds identified via UPLC-PDA/MS in Tt fractions with the active site of acetylcholinesterase (AChE) were explored via molecular docking analyses. Terrestrosin C, protodioscin, rutin, and saponin C exhibited the most stable binding. The spatial memory performance was assessed using the Y-maze test, and memory recognition was examined using a novel object recognition (NOR) test. Tt extract treatment reversed the altered locomotion patterns that were caused by SCOP administration. Biochemical analyses also verified Tt's role in inhibiting AChE, improving antioxidant enzyme activities, and reducing oxidative stress markers. The present findings pave the way for future application of Tt as a natural alternative to treat cognitive disorders.

THE INFLUENCE OF MESENCHYMAL STEM CELLS ON THE DYNAMICS OF REGULATOR OF ENDOTHELIAL PROLIFERATION EXPRESSIONS IN THE BRAIN STRUCTURES OF RATS WITH EXPERIMENTAL ALZHEIMER-TYPE DEMENTIA

Background. Despite numerous studies, the assessment of the functional state of the vascular endothelium by determining the localization of cells, producers of the endothelial proliferation factor, and measuring the intensity of its production in the brain of rats with dementia of Alzheimer type is of great relevance.&#x0D; Objective: to investigate the impact of mesenchymal stem cells on the functional state of the endothelium of brain vessel in rats with Alzheimer-type dementia by assessing the optical density of brain structures expressing the endothelial proliferation factor.&#x0D; Results. In neurons of the CA1 zone of the hippocampus in gr. SС-14 and in In SС-28, SС-28-MSC, the optical density of cytoplasm marked by endothelial proliferation factor, compared to the control, was 3.6, 1.5, and 2.0 times lower, respectively, and in cortical neurons it did not differ from the control level. After injections of mesenchymal stem cells in all studied groups, there was a decrease in the optical density of labeled factor proliferation of the endothelium of the cytoplasm of cortical neurons and more significantly - in hippocampus neurons (especially in the SС-14-MSC group).&#x0D; Conclusions. In rats with scopolamine-induced dementia of the Alzheimer's type, after 14 days of the "regeneration" period, compared to controls the expression level of vascular factor in hippocampal neurons was significantly lower than that in cortical neurons, which is associated with their greater degree of damage depending on the duration of scopolamine administration, Less active production and more significant reception of endothelial proliferation factor by endotheliocytes was accompanied by a decrease in the optical density of the correspondingly labeled plasma. The introduction of mesenchymal stem cells, probably due to stimulation by the growth factors in them, leads to the activation of the proliferation of the vascular endothelium and a decrease in the synthesis of the own factor of endothelial proliferation.