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Introduction: The pathophysiological mechanism of Alzheimer's disease (AD) has not been clearly identified, and effective treatment methods have not yet been established. Scopolamine causes cholinergic dysfunction in the brain, including the accumulation of amyloid-beta plaques, thereby increasing oxidative stress and neuroinflammation, mimicking AD. Glial cells such as astrocytes have recently been identified as possible biomarkers for AD. Photobiomodulation (PBM) elicits a beneficial biological response in cells and tissues. PBM effects on the central nervous system (CNS) have been widely researched, including effects on astrocyte activity. Methods: In the present study, PBM was performed using light at the nearinfrared wavelength of 825 nm. The Morris water maze and Y-maze tests were employed to evaluate cognitive function decline in a scopolamineinduced memory dysfunction model and its improvement with PBM. In addition, alteration of the mitogen-activated protein kinase (MAPK) pathway and immunofluorescence expression levels of active astrocytes were observed in the hippocampus, which is one of the areas affected by AD, to evaluate the mechanism of action of PBM. Results: A reduction in the neuronal cell death in the hippocampus caused by scopolamine was observed with PBM. Moreover, alteration of a MAPK pathwayrelated marker and changes in glial fibrillary acidic protein (an active astrocyte marker) expression were observed in the PBM-treated group. Finally, significant correlations between functional and histological results were found, validating the results. Discussion: These findings indicate the possibility of behavioral and histological improvement due to PBM in scopolamine-induced CNS alteration, which mimics AD. This improvement could be related to neuroinflammatory modulation and altered astrocyte activity. [ABSTRACT FROM AUTHOR]

The article discusses a retracted study on the potential of Santacruzamate A (STA) in treating Alzheimer's disease (AD) by targeting endoplasmic reticulum (ER) stress pathways. The study found that STA could alleviate Aβ-induced toxicity in cells and improve cognitive deficits in mice by modulating ER stress and apoptotic pathways. By inhibiting unfolded protein response (UPR) and ER stress, STA showed promise in treating AD by regulating ER retention signal receptors and mitochondrial assembly proteins. The findings suggest that STA, a carbamate derivative, may hold potential in treating neurodegenerative disorders by targeting ER stress pathways. [Extracted from the article]

Background/Objectives: Alzheimer's disease (AD) is an age-related degenerative brain disorder characterized by a progressive decline in cognitive function and memory. This study aimed to evaluate whether rutin hydrate (RH) has neuroprotective effects in an AD-like learning and memory impairment rat model induced by scopolamine (SCO). Methods: The rats were administered with RH (100 mg/kg) and SCO (1.5 mg/kg) and underwent behavioral tests, including the Morris water maze test, Y-maze test, and passive avoidance test, to evaluate their learning and memory abilities. Additionally, long-term potentiation (LTP) was induced to observe changes in the field excitatory postsynaptic potential (fEPSP) activity. Results: RH treatment attenuated the SCO-induced shortening of step-through latency in the passive avoidance (PA) test, increased the percentage of alternation in the Y-maze, and increased the time spent in the target zone in the Morris water maze (MWM). Moreover, RH increased the total activity of fEPSP following theta burst stimulation and attenuated the SCO-induced blockade of fEPSP. RH also ameliorated the SCO-induced decrease in the expression levels of the BDNF, TrkB, ERK, CREB, and Bcl-2 proteins and the increase in the Bax protein level in the rat hippocampus. This demonstrates that RH has beneficial neuroprotective effects in the brain, improving learning, memory, and synaptic plasticity in rats. Conclusions: Our results highlight the molecular and cellular mechanisms through which RH exerts its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders. RH could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD. [ABSTRACT FROM AUTHOR]

Asiatic acid (AA) has previously shown its neuroprotective effects, but low oral bioavailability limits its penetration into the brain. This study aimed to investigate the effect of intranasal AA administration in mice with memory dysfunction induced by scopolamine. Mice received either intranasal AA (INAA), oral AA (POAA3 or POAA30), or donepezil, followed by scopolamine for 10 days. Morris water maze (MWM) was performed on days 0–5, 30 min after treatment. Locomotor activity was conducted on day 6 followed by brain collection. In MWM, INAA treatment had significantly reduced escape latency on days 2–4, while POAA3 decreased escape latency on day 3 and POAA30 and donepezil decreased escape latency on day 4. INAA inhibited acetylcholinesterase activity, increased catalase protein expression, and decreased malondialdehyde levels in the brain tissue. Therefore, intranasal administration of AA produced a rapid onset in the protection of learning and memory deficits induced by scopolamine through acetylcholinesterase inhibition and antioxidant effect. [ABSTRACT FROM AUTHOR]

Background and Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: The neuroprotective properties of PFE are highlighted, suggesting its potential as a promising treatment strategy for AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Agastache rugosa, a traditional Asian herbal medicine, is primarily used for digestive problems; yet, its cognitive benefits remain unexplored. This study evaluated the anti-amnesic effects of A. rugosa extract (ARE) on scopolamine (SCO)-induced memory impairment in mice. Mice received 100 or 200 mg/kg ARE orally for 5 days, followed by SCO injection. The ARE demonstrated significant antioxidant (DPPH IC50: 75.3 µg/mL) and anti-inflammatory effects (NO reduction). Furthermore, the ARE significantly improved memory performance in the passive avoidance test (escape latency: 157.2 s vs. 536.9 s), the novel object recognition test (novel object preference: 47.6% vs. 66.3%) and the Morris water maze (time spent in the target quadrant: 30.0% vs. 45.1%). The ARE reduced hippocampal acetylcholinesterase activity (1.8-fold vs. 1.1-fold) while increasing choline acetyltransferase (0.4-fold vs. 1.0-fold) and muscarinic acetylcholine receptor subtype I (0.3-fold vs. 1.6-fold) expression. The ARE improved hippocampal neurogenesis via doublecortin- (0.4-fold vs. 1.1-fold) and KI-67-positive (6.3 vs. 12.0) cells. Therefore, the ARE exerts protective effects against cognitive decline through cholinergic system modulation and antioxidant activity, supporting its potential use as a cognitive enhancer. [ABSTRACT FROM AUTHOR]

While Ginsenoside Re has been shown to protect the central nervous system, reports of its effects on memory in the model of scopolamine-induced memory impairment are rare. The aim of this study was to investigate the effects of Ginsenoside Re on scopolamine (SCOP)-induced memory damage and the mechanism of action. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days and with or without Ginsenoside Re for 14 days. As evidenced by behavioral studies (escape latency and cross platform position), brain tissue morphology, and oxidative stress indicators after Ginsenoside Re treatment, the memory damage caused by SCOP was significantly ameliorated. Further mechanism research indicated that Ginsenoside Re inhibited cell apoptosis by regulating the PI3K/Akt/Nrf2 pathway, thereby exerting a cognitive impairment improvement effect. This research suggests that Ginsenoside Re could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress and cell apoptosis.

Background/Objectives: Alzheimer’s disease (AD) is an age-related degenerative brain disorder characterized by a progressive decline in cognitive function and memory. This study aimed to evaluate whether rutin hydrate (RH) has neuroprotective effects in an AD-like learning and memory impairment rat model induced by scopolamine (SCO). Methods: The rats were administered with RH (100 mg/kg) and SCO (1.5 mg/kg) and underwent behavioral tests, including the Morris water maze test, Y-maze test, and passive avoidance test, to evaluate their learning and memory abilities. Additionally, long-term potentiation (LTP) was induced to observe changes in the field excitatory postsynaptic potential (fEPSP) activity. Results: RH treatment attenuated the SCO-induced shortening of step-through latency in the passive avoidance (PA) test, increased the percentage of alternation in the Y-maze, and increased the time spent in the target zone in the Morris water maze (MWM). Moreover, RH increased the total activity of fEPSP following theta burst stimulation and attenuated the SCO-induced blockade of fEPSP. RH also ameliorated the SCO-induced decrease in the expression levels of the BDNF, TrkB, ERK, CREB, and Bcl-2 proteins and the increase in the Bax protein level in the rat hippocampus. This demonstrates that RH has beneficial neuroprotective effects in the brain, improving learning, memory, and synaptic plasticity in rats. Conclusions: Our results highlight the molecular and cellular mechanisms through which RH exerts its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders. RH could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD.

Background and Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: The neuroprotective properties of PFE are highlighted, suggesting its potential as a promising treatment strategy for AD.

Simple Summary: High-resolution magnetic resonance imaging (MRI) is essential for detecting subtle pathologies in the bladder, but it can be affected by movement from peristalsis of the urinary, gastrointestinal, and reproductive systems. Spasmolytics such as buscolysin and glucagon help to reduce motion artifacts, potentially leading to clearer images. The aim of our study was to analyze and compare the properties, benefits, and side effects of these substances to improve patient preparation for bladder MRI exams. Although both substances have similarities, butylscopolamine is preferred due to its lower cost, with glucagon serving as an alternative for those with medical contraindications. We also reviewed recent studies on the use of spasmolytics in MRI of pelvic organs. Our findings indicate that the inconsistent results regarding the utility of spasmolytics highlight the need for further research to determine whether their application truly enhances MRI accuracy and quality for the examination and staging process. Accurate assessment of muscular layer infiltration of the urinary bladder wall is crucial for diagnostic precision and is significantly influenced, among other factors, by the elimination of motion artifacts. This review explores the potential benefits of using spasmolytic agents to achieve improved imaging results. Specifically, it examines two commonly available pharmaceutical preparations: butylscopolamine (buscolysin) and glucagon. The review highlights the similarities and differences between these agents and discusses the optimal methods of administration to enhance urinary bladder imaging. By addressing these factors, the article aims to provide insights into improving diagnostic accuracy in clinical practice. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder, marked by cognitive impairment. Currently, the available treatment provides only symptomatic relief and there is a great need to design and formulate new drugs to stabilize AD. In the search for a new anti-Alzheimer's drug, 3,5-bis(2-hydroxyethyl)-1,3,5-thiadiazinane-2-thione (THTT), a tetrahydro-2H-1,3,5-thiadiazine-2-thione derivative, was investigated against a scopolamine-induced Alzheimer's model. The selected test compound was administered intraperitoneally in three doses (15 mg/kg, 30 mg/kg, and 45 mg/kg). The test compound exhibited an IC50 value of 69.41 µg/mL, indicating its ability to inhibit the acetylcholinesterase enzyme. An antioxidant DPPH assay revealed that the IC50 value of the test compound was 97.75 µg/mL, which shows that the test compound possesses antioxidant activity. The results of behavior tests including the Y-maze and elevated plus maze (EPM) show that the test compound improved short-term memory and spatial memory, respectively. Furthermore, in the Morris water maze (MWM) and light/dark model, the test compound shows improvements in learning and memory. Moreover, the results of histological studies show that the test compound can protect the brain against the harmful effects of scopolamine. Overall, the findings of our investigation suggest that our chosen test compound has disease-modifying and neuroprotective activities against the scopolamine-induced Alzheimer's model. The test compound may be beneficial, subject to further elaborate investigation for anti-amyloid disease-modifying properties in AD. [ABSTRACT FROM AUTHOR]

One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with onboard memory for direct high-resolution recording of brain activity for >48 h. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). The mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between the drug treatments. Hypoactivity was globally observed as a consistent outcome in the MK801-treated mice and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological, and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in, e.g., drug discovery and models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes. [ABSTRACT FROM AUTHOR]

Population aging around the world is rapidly progressing; as a result, cognitive decline developing into dementia is becoming a social problem. There is no drug that can cure dementia, and though drugs that alleviate the symptoms of dementia have been developed, they also have side effects. Therefore, we conducted a study on improving cognitive function using natural products that have secured safety. We confirmed the effect of an extract of Scrophularia buergeriana on scopolamine-induced cognitive impairment through mouse behavioral experiments, and we observed metabolic changes in the cortex and hippocampus via brain tissue dissection after the behavioral experiment. Mitigating effects of S. buergeriana on cognitive impairment caused by scopolamine were observed in passive avoidance and Morris water maze tests. A metabolic analysis revealed biomarkers related to the alleviating effect of cognitive impairment. Niacinamide, tyrosine, uridine, and valine in the cortex and GABA, choline, creatine, formate, fumarate, hypoxanthine, leucine, myo-inositol, pyroglutamate, and taurine in the hippocampus were identified as biomarker candidates for recovering cognitive impairment. In addition to behavioral experiments, this metabolomics study using specific regions of the brain may be helpful in understanding the effects of cognitive improvement. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's Disease (AD) is the most prevalent cause of dementia globally and its frequency increases as the world's population ages. AD is one of the largest healthcare issues of the 21st century as the primary cause of dementia and neurodegenerative illnesses. An acquired loss of cognitive function across many cognitive areas is referred to as dementia. The animal studies conducted in this research article to determine whether chemical compounds cause AD may be useful in understanding the disease's mechanism and treatment options. Objectives: The current study assessed the effectiveness of C-Phycocyanin (C-PC) from Spirulina platensis and ethanolic extract of Clerodendreme inerme against scopolamine-induced Alzheimer's in mice. Since Clerodendreme inerme and C-PC are rich in active chemical constituents, they function as beneficial antioxidants. These constituents include saponins, oil, fat, phenolic compounds, tannins, alkaloids, flavonoids, glycosides, terpenoids, steroids, amino acids, proteins and carbs. Thus, an assessment of the anti-Alzheimer properties of the ethanolic extract from Clerodendreme inerme and C-Phycocyanin from Spirulina platensis was conducted. Materials and Methods: The study was designed to evaluate prophylactic effect of Spirulina platensis and Clerodendreme inerme against Scopolamine induced Alzheimer's in mice. Piracetam (200 mg/kg) was used as a standard. The extracts from the plant and leaves of Spirulina platensis and Clerodendreme inerme were screened for anti-alzheimer potential in scopolamine induced Alzheimer's in mice by administering 0.4 mg/kg b.w/day i.p. as test dose. Behavioral Assessments as well as serum levels of AchE, in vitro and Bio-chemical parameters were assessed. Results: Treated with ethanolic extracts of Clerodendreme inerme, C-PC of Spirulina platensis, it demonstrated a dose-dependent reduction in escape latency time and an increase in time spent in the target quadrant. Clerodendreme inerme and C-PC of Spirulina platensis both reduce the escape latency time and transfer latency time in EPM in a dose-dependent manner. AD rodents treated with ethanolic extracts of Clerodendreme inerme, C-PC of Spirulina platensis demonstrated a dose-dependent rise in percentage change in the Y maze test. Apart from behavioral assessments, extracts from ethanolic extract of Clerodendreme inerme, SP demonstrated a dose-dependent decrease in AchE level, since the loss of ACh resulting from AChE's hydrolytic action causes cognitive impairment. AD rodents that were pretreated with ethanolic extract of Clerodendreme inerme, SP there is an increase in catalase and lipid peroxidation. Conclusion: The study concludes that Spirulina platensis and Clerodendreme inerme extracts have a significant anti-Alzheimer activity. This is likely because the extracts contain a variety of nutrients, including saponins, oil, fat, phenolic compounds, tannins, alkaloids, flavonoids, glycosides, terpenoids, amino acids, steroids, proteins and carbs. [ABSTRACT FROM AUTHOR]

Introduction: Hyoscyamus muticus L. subsp falezlez (Coss.) Maire is a Saharan species rich in tropane alkaloids (especially hyoscyamine). Hyoscyamine is raced into atropine, whose interest in pharmacy is considerable. The objective is to dose Hyoscyamus muticus L. subsp falezlez (Coss.) Maire alkaloids from the stations of Algerian Sahara (Abadla, Adrar, and Tamanrasset), to exploit the data in the valorization of this species as a potential source of industrial production of atropine. Method: The determination of tropane alkaloids (Hyoscyamine and scopolamine) concerned the whole plant (spontaneous and cultivated) and the various organs and was carried out by colorimetric method and High-performance liquid chromatography (HPLC). Results: The colorimetric assay showed that the highest level of alkaloids was observed in the Adrar Sbaa station (2.83 %) in the leaf organ. However, the stem organ showed an average level of alkaloids in all harvesting stations (from 0.5 to 0.98 %). The HPLC assay confirmed the alkaloid and hyoscyamine richness in all study stations for spontaneous plant and cultivated species. The plant of the two stations (Tamanrasset and Adrar Sbaa) stood out with grades reaching (6.693±0.555 mg/100gDM and 4.707±0.092 mg/100gDM) respectively, and a hyoscyamine rate of (5.765± 0.23 mg/100gDM) for the Tamanrasset station. Conclusions: At the end of our study and the content of the results obtained on Hyoscyamus muticus subsp falezlez (Coss.) Maire of Algeria, it is imperative to exploit this species as an industrial source of atropine production in Algeria [ABSTRACT FROM AUTHOR]

Both hypertension and aging are known to increase the vulnerability of the brain to neurovascular damage, resulting in cognitive impairment. The present study investigated the efficacy of the antihypertensive drug losartan on age- and hypertension-associated cognitive decline and the possible mechanism underlying its effect in spontaneously hypertensive rats (SHRs). Losartan was administered (10 mg/kg, i.p. for 19 days) to 3- and 14-month-old SHRs. Age-matched Wistar rats were used as controls. Working memory, short-term object recognition, and spatial memory were assessed using the Y-maze, object recognition test (ORT) and radial arm maze (RAM) test. The expression of markers associated with aging, oxidative stress, and memory-related signaling was assessed in the frontal cortex (FC) and hippocampus. Motor activity measured over 24 h was not different between groups. Middle-aged vehicle-treated SHRs showed poorer performance in spontaneous alternation behavior (SAB) and activity in the first Y-maze test than their younger counterparts, suggesting age-related reduced "decision making" and reactivity in a novel environment. Losartan improved the age- and hypertension-induced decline in short-term recognition and spatial memory measured in the ORT and the second Y-maze test, particularly in the middle-aged rats, but was ineffective in the young adult rats. Changes in memory and age-related markers such as cAMP response element-binding protein (CREB) and amyloid-β1–42 (Aβ1–42) and increased oxidative stress were observed in the hippocampus but not in the FC between young adult and middle-aged vehicle-treated SHRs. Losartan increased CREB expression while reducing Aβ1–42 levels and concomitant oxidative stress in middle-aged SHRs compared with vehicle-treated SHRs. In conclusion, our study highlights the complex interplay between hypertension, aging, and cognitive impairment. It suggests that there is a critical time window for therapeutic intervention with angiotensin II type 1 receptor blockers. [ABSTRACT FROM AUTHOR]

Background: The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused. Methods: In this study, we used in vivo and in vitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)‐induced cognitive dysfunction. The behavioral tests were performed. 18F‐FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the in vitro experiments. Results: We found that melatonin could ameliorate SCOP‐induced cognitive dysfunction and relieve anxious‐like behaviors or HT22 cell damage. 18F‐FDG PET‐CT results showed that melatonin could improve cerebral glucose uptake in SCOP‐treated mice. Melatonin restored the cholinergic function, increased the expressions of neurotrophic factors, and ameliorated oxidative stress in the brain of SCOP‐treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol‐requiring enzyme (p‐IRE1α) and its downstream, X‐box binding protein 1 (XBP1). Conclusions: These results indicated that melatonin could ameliorate SCOP‐induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC50 of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood–brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile. [ABSTRACT FROM AUTHOR]

Petitgrain essential oil (PGEO) is derived from the water distillation process on mandarin (Citrus reticulata) leaves. The chemical constituents of PGEO were analyzed by gas chromatography/mass spectrometry (GC/MS) method which revealed the presence of six compounds (100%). The major peaks were for methyl-N-methyl anthranilate (89.93%) and γ-terpinene (6.25%). Over 19 days, zebrafish (Tubingen strain) received PGEO (25, 150, and 300 μL/L) before induction of cognitive impairment with scopolamine immersion (SCOP, 100 μM). Anxiety-like behavior and memory of the zebrafish were assessed by a novel tank diving test (NTT), Y-maze test, and novel object recognition test (NOR). Additionally, the activity of acetylcholinesterase (AChE) and the extent of the brain's oxidative stress were explored. In conjunction, in silico forecasts were used to determine the pharmacokinetic properties of the principal compounds discovered in PGEO, employing platforms such as SwissADME, Molininspiration, and pKCSM. The findings provided evidence that PGEO possesses the capability to enhance memory by AChE inhibition, alleviate SCOP-induced anxiety during behavioral tasks, and diminish brain oxidative stress. [ABSTRACT FROM AUTHOR]

Simple Summary: Cognitive deficits, including spatial working and recognition memory impairment, are a common feature of Alzheimer's disease with current therapies offering limited efficacy. Marrubium vulgare, a member of the Lamiaceae family, has shown potential to alleviate spatial memory impairment in a model of experimental dementia in rats through its antioxidant and acetylcholinesterase inhibitory activities. The aim of this study was to examine the effect of M. vulgare on recognition memory in healthy and dementia-affected rats after 21 days of oral administration. Memory performance was evaluated by the novel object recognition test. Levels of neurotransmitters acetylcholine, noradrenaline (NA), and serotonin, as well as the protein expression of the brain-derived neurotrophic factor (BDNF) and the phosphorylation of the cAMP response element-binding protein (p-CREB), were measured. The expression levels of BDNF and CREB were evaluated via RT-PCR in the cortex and hippocampus. Our result revealed that M. vulgare ameliorated recognition memory impairment in dementia rats by preserving cholinergic function in the hippocampus, increasing NA levels in the brain, and restoring pCREB expression in the cortex following their reduction in the experimental model used. In healthy rats, the extract upregulated the expression of BDNF and pCREB in the cortex. These findings suggest that M. vulgare has potential as a therapeutic agent for cognitive impairments in various neurodegenerative diseases. The potential of Marrubium vulgare to alleviate scopolamine (Sco)-induced deficits in spatial working memory has drawn considerable scientific interest. This effect is partly attributed to its potent antioxidant and acetylcholinesterase inhibitory (AChEI) activities. This study examined the effects of M. vulgare extract, standardized to marrubiin content, on recognition memory in healthy and Sco-treated rats. Male Wistar rats (200–250 g) were divided into four groups. The extract was orally administered for 21 days and Sco (2 mg/kg) was intraperitoneally injected for 11 consecutive days. Memory performance was assessed using the novel object recognition test. Levels of acetylcholine (ACh), noradrenaline (NA), serotonin (Sero), and brain-derived neurotrophic factor (BDNF) and the phosphorylation of cAMP response element-binding protein (p-CREB) were evaluated in the cortex and hippocampus via ELISA. BDNF and CREB expression levels were assessed using RT-PCR. The results showed that M. vulgare significantly alleviated Sco-induced memory impairment, preserved cholinergic function in the hippocampus, increased NA levels in the brain, and restored pCREB expression in the cortex following Sco-induced reduction. In healthy rats, the extract upregulated BDNF, pCREB, and Bcl2 expression. Our findings indicate that the neuroprotective effects of M. vulgare may be linked to the modulation of cholinergic function, regulation of NA neurotransmission, and influence on key memory-related molecules. [ABSTRACT FROM AUTHOR]

A plethora of pathophysiological events have been shown to play a synergistic role in neurodegeneration, revealing multiple potential targets for the pharmacological modulation of Alzheimer's disease (AD). In continuation to our previous work on new indole- and/or donepezil-based hybrids as neuroprotective agents, the present study reports on the beneficial effects of lead compounds of the series on key pathognomonic features of AD in both cellular and in vivo models. An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the anti-fibrillogenic properties of 15 selected derivatives and identify quantitative changes in the formation of neurotoxic β-amyloid (Aβ42) species in human neuronal cells in response to treatment. Among the most promising compounds were 3a and 3c, which have recently shown excellent antioxidant and anticholinesterase activities, and, therefore, have been subjected to further in vivo investigation in mice. An acute toxicity study was performed after intraperitoneal (i.p.) administration of both compounds, and 1/10 of the LD50 (35 mg/kg) was selected for subacute treatment (14 days) with scopolamine in mice. Donepezil (DNPZ) and/or galantamine (GAL) were used as reference drugs, aiming to establish any pharmacological superiority of the multifaceted approach in battling hallmark features of neurodegeneration. Our promising results give first insights into emerging disease-modifying strategies to combine multiple synergistic activities in a single molecule. [ABSTRACT FROM AUTHOR]

A miniaturized solid-phase extraction of two tropane alkaloids (TAs) and twenty-one pyrrolizidine alkaloids (PAs) from infusions of dry edible flowers using optimized µSPEed® technique was developed. The optimization of the µSPEed® methodology involved testing different cartridges and comparing various volumes and numbers of loading cycles. The final conditions allowed for a rapid extraction, taking only 3.5 min. This was achieved using a C18-ODS cartridge, conditioning with 100 µL of methanol (two cycles), loading 100 µL of the infusion sample (seven cycles), and eluting the analytes with 100 µL of methanol (two cycles). Prior to their analysis by UHPLC-IT-MS/MS, the extracts were evaporated and reconstituted in 100 µL of water (0.2% formic acid)/methanol (0.2% ammonia) 95:5 (v/v), allowing for a preconcentration factor of seven times. The methodology was successfully validated obtaining recoveries ranging between 87 and 97%, RSD of less than 12%, and MQL between 0.09 and 0.2 µg/L. The validated methodology was applied to twenty samples of edible flower infusions to evaluate the safety of these products. Two infusion samples obtained from Acmella oleracea and Viola tricolor were contaminated with 0.16 and 0.2 µg/L of scopolamine (TA), respectively, while the infusion of Citrus aurantium was contaminated with intermedine and lycopsamine (PAs) below the MQL. [ABSTRACT FROM AUTHOR]

Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), β-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-β (Aβ), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis. [ABSTRACT FROM AUTHOR]

The retention behaviour of scopolamine (hyoscine) and its related compounds (norhyoscine, atropine, homatropine, and noratropine) was investigated on the silica-based HPLC stationary phase. The retention of investigated tropane alkaloids was interpreted by using the Soczewiński-Wachtmeister equation. A high correlation between the retention parameter (log k) and lipophilicity (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of the aforementioned compounds. It was found that by increasing the acetonitrile fraction, a decrease in retention of the more polar epoxide derivatives (scopolamine, norhyoscine) and an increase in retention of the more lipophilic derivatives (atropine, noratropine, homatropine) is obtained. The best separation of the tropane alkaloids was achieved by a simple procedure that involved a mobile phase composed of acetonitrile and 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50 v/v. Selected conditions were assumed for the determination of scopolamine hydrochloride in the eye drops (Scopolamini hydrobromidum 0.25%). The method was validated and it was found as selective, sensitive, precise, accurate, and robust for the further qualitative analysis of the scopolamine-related compounds. [ABSTRACT FROM AUTHOR]

Aversive stimuli can cause hippocampal place cells to remap their firing fields, but it is not known whether remapping plays a role in storing memories of aversive experiences. Here, we addressed this question by performing in vivo calcium imaging of CA1 place cells in freely behaving rats (n = 14). Rats were first trained to prefer a short path over a long path for obtaining food reward, then trained to avoid the short path by delivering a mild footshock. Remapping was assessed by comparing place cell population vector similarity before acquisition versus after extinction of avoidance. Some rats received shock after systemic injections of the amnestic drug scopolamine at a dose (1 mg/kg) that impaired avoidance learning but spared spatial tuning and shock-evoked responses of CA1 neurons. Place cells remapped significantly more following remembered than forgotten shocks (drug-free versus scopolamine conditions); shock-induced remapping did not cause place fields to migrate toward or away from the shocked location and was similarly prevalent in cells that were responsive versus non-responsive to shocks. When rats were exposed to a neutral barrier rather than aversive shock, place cells remapped significantly less in response to the barrier. We conclude that place cell remapping occurs in response to events that are remembered rather than merely perceived and forgotten, suggesting that reorganization of hippocampal population codes may play a role in storing memories for aversive events.

Background: Scopolamine is an anticholinergic drug that disrupts cholinergic transmission in the central nervous system as well as causes cognitive abnormalities and pathological hallmarks that are similar to those seen in Alzheimer’s Disease. Therefore, it is used for induction of Alzheimer’s Disease in animal models. Objective: to investigate the effects of long-term induction with scopolamine on the brain tissue of mice. Methods: Seventy adult mice were divided into 2 equal groups: The first group was the normal control group received distilled water only. The second one was the Alzheimer’s Disease induction group received intraperitoneal scopolamine (1mg/kg) for 14 days only after that distilled water was given for the next 6 months. Ten mice were isolated from each group at zero time, after 2 weeks of induction, after 3-month and after 6 months and subjected to the behavioral tests then sacrificed for determination of biochemical factors (including brain-derived neurotrophic factor, total antioxidant status, malondialdehyde, and amyloid β). Data were analyzed using t-tests, and ANOVA. All values expressed as Mean±SD and P value

Aim: The present study was to assess the anti-amnesic effect of Actinidia chinensis var deliciosa in a rat model of scopolamine-induced amnesia. Method: 36 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. Result: Scopolamine-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.

Background and purpose: 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. Experimental approach: 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). Findings/Results: 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. Conclusions and implications: 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.

Abstract Background Alzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes. Results The current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test. When compared to the illness control, the memory-enhancing potential of novel N-benzyl pyridine-2-one derivatives was highly significant (P

Objective: The present study examined effects of resistance training (RT) and resveratrol (RES) alone and together on acrylamide (AC)-induced memory impairment in rats.Materials and Methods: Animals were divided into 6 groups: (1) Control group which received normal saline intraperitoneally (ip) daily for 8 weeks; (2) Scopolamine (SCO) group which received SCO (1 mg/kg/day, ip) for 8 weeks; (3) AC group which received AC (5 mg/kg/day, ip) for 8 weeks; (4) AC + RT group which received AC (5 mg/kg/day, ip) for 8 weeks and performed RT (5 days a week for 8 weeks); (5) AC + RES group which received AC (5 mg/kg/day, ip) and RES (1 mg/kg/day, ip) for 8 weeks; and (6) AC + RT + RES group which received AC (5 mg/kg/day, ip) and RES (1 mg/kg/day, ip) for 8 weeks and performed RT (5 days a week for 8 weeks). On day 53, animal training began in the Morris Water Maze (MWM) and 24 hr after the last training, the probe test was performed.Results: RT and RES alone did not significantly affect escape latency or traveled distance increased by AC. However, concomitant RES and RT treatment significantly reduced these parameters compared to the AC group. Co-treatment with RES and RT also significantly increased the time spent in the target quadrant compared to the AC group. Lipid peroxidation was reduced in the AC+RES and AC+RT+RES groups compared to the AC group. Conclusion: It seems that daily co-treatment with RES and RT for 8 weeks ameliorates the memory-impairing effects of AC.

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 aim of the study was to compare the effect of three substances with ecbolic activity, Oxytocin, Prostaglandin F2α (PGF2α) and Scopolamine, on the uterine involution process in dairy cows and on the resumption of ovarian activity. Eighty bovine were randomly divided in four groups: GROUP C: 20 cows treated, within 24 h of calving, with 5 mL/head of saline solution; GROUP PG: 20 cows treated, within 24 h of calving, with 150 µg/head of d-cloprostenol; GROUP OX: 20 cows treated, within 24 h of calving, with 50 IU/head of oxytocin acetate; GROUP S: 20 cows treated, within 24 h of calving, with 40 mg/q Scopolamine Butylbromide. Each cow was subjected to blood samples to evaluate the Hydroxyproline (HYP) levels, at T0, within 24 h after calving, and T7, T14, T28, 7, 14, and 28 days after calving, respectively. At T14 and T28, an ultrasound examination was performed to measure the diameter of expregnant horn. In all cows, the reproductive indices (days to first service and number of artificial insemination for conception) were evaluated. In all groups, the HYP concentrations have been rising from T0 to T28, with the maximum levels obtained at T28 in the groups PG and S. As regard the diameter of uterine horn, the comparison among the groups showed significant differences only at T28, with lower values in the group PG and S. In group S and PG, the days to first service were less than other groups. Treatment with Scopolamine and PGF2α resulted in better outcomes, evidenced clinically by more efficient uterine involution and faster ovarian recovery. [ABSTRACT FROM AUTHOR]

In the investigation of active ingredients from natural products, current technologies relying on drug–target affinity recognition analysis face significant challenges. This is primarily due to their limited specificity and inability to provide downstream pharmacodynamic information, such as agonistic or antagonistic activity. In this study, a two-point method was developed by immobilizing M3 acetylcholine receptor (M3R) through the combination of the conformation-specific peptide BJ-PRO-13a and the HaloTag trap system. We systematically assessed the specificity of the immobilized M3R using known M3R antagonists (pirenzepine and atropine) and agonists (cevimeline and pilocarpine). By frontal analysis and nonlinear chromatography, the performance of immobilized M3R was evaluated in terms of binding kinetics and thermodynamics of four drugs to the immobilized M3R. Additionally, we successfully identified two M3R antagonists within an extract from Daturae Flos (DF), specifically hyoscyamine and scopolamine. Our findings demonstrate that this immobilization method effectively captures receptor-ligand binding interactions and can discern receptor agonists from antagonists. This innovation enhances the efficiency of receptor chromatography to determine binding-affinity in the development of new drugs, offering promise for the screening and characterization of active compounds, particularly within complex natural products. [ABSTRACT FROM AUTHOR]

Tropane alkaloids (TAs) are the main secondary metabolites found in Datureae (Solanaceae). These compounds are neurotoxic to many organisms. However, some insect species can sequester and accumulate TAs in their bodies. Brugmansia suaveolens (Humb. and Bonpl. ex Willd.) Bercht. and J.Presl, a Neotropical shrub, is known to produce TAs. In this study, we report the sequestration of TAs from B. suaveolens by Chromacris speciosa (Thunberg, 1824) (Orthoptera: Rhomaleidae) and Lema daturaphila Kogan & Goeden (Coleoptera: Chrysomelidae). Both of these insects have been observed feeding on leaves from various species of Solanaceae in the study site. We analyzed extracts from insects and the host plant using gas chromatography and mass spectrometry (GC-MS). In B. suaveolens, we identified five TAs, while in the insect bodies, we found four. Scopolamine was the most abundant alkaloid in all the samples. This is the first report of TAs in these insects. While TAS may play a role in defense against generalist herbivores, further investigation is needed to understand the association between TAs and predators since both insects exhibit moderately aposematic features. [ABSTRACT FROM AUTHOR]