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AbstractBackgroundObjectivesMaterial and methodsResultsConclusionSignificanceScopolamine has been demonstrated to relieve motion sickness. However, repeated significance testing may increase false-positive results.Review the efficacy and safety of scopolamine in the prevention of motion sickness by performing a meta-analysis with Trial Sequential Analysis (TSA).Randomized controlled trials (RCTs) compared scopolamine with other medications or placebo were included. Primary outcomes were nausea reported and head movement time.Twenty studies with 753 participants were included. Scopolamine had a greater reported reduction in nausea than placebo (relative risk [RR] 0.35; 95% confidence interval [CI] 0.24 to 0.52; p<0.00001; I2 = 45%), while TSA showed the included sample size exceeded the required information size (RIS). There is no difference in head movement time between scopolamine and placebo (mean difference [MD] 2.02; 95% CI −1.2 to 5.25; p = 0.6; I2 = 0%), while the included sample size did not reach RIS.Scopolamine is effective for motion sickness nausea compared to placebo. The TSA recommends conducting more head movement trials to validate the objective efficacy of scopolamine.Clarifying the efficacy of scopolamine for motion sickness, the TSA highlights the need for more prospective studies using head movement as an outcome. [ABSTRACT FROM AUTHOR]

This study aimed to assess the incidence of post‐discharge nausea and vomiting (PDNV) following sedation with nalbuphine and etomidate and to evaluate the prophylactic effects of scopolamine in reducing PDNV. A two‐stage prospective clinical trial was conducted. The first part involved an observational study of 77 subjects to assess the PDNV incidence post‐sedation with nalbuphine, etomidate, and propofol. The second part compared the effectiveness of palonosetron 0.075 mg (P group), scopolamine 0.1 mg (S group), and their combination (PS group) in reducing PDNV. The primary endpoint was the incidence of PDNV within 8 h post‐sedation. Secondary outcomes included PDNV frequency and severity at 8–24, 0–24, and 24–48 h and side effects of medications. The incidence of PDNV within 8 h post‐sedation was 37.66% (29/77). The PS group showed a significantly lower PDNV rate of 2.56% within 8 h, compared to the P group (35.71%, P < .001), S group (19.64%, P < .001), and control group (38.39%, P < .001), respectively. The S group (19.64%) also had a lower rate than the P group (35.71%, P = .007) and the control group (38.39%, P = .002). Subgroup analysis suggested a potential differential effect of palonosetron in reducing vomiting among male patients undergoing gastrointestinal procedures. The combination therapy was also associated with fewer cases of mild or no nausea and vomiting. In summary, the incidence of PDNV following sedation with nalbuphine and etomidate was notably high. The combination of scopolamine and palonosetron was more effective in preventing PDNV, with implications for improved post‐sedation care. [ABSTRACT FROM AUTHOR]

To establish and characterize a dry eye model in New Zealand rabbits by subcutaneous injections of scopolamine hydrobromide (SCOP). Twenty New Zealand male rabbits were injected subcutaneously SCOP for 14 consecutive days; subcutaneous saline was used as a negative control. The correlated clinical parameters of ocular surface dryness were detected in vivo using tear secretion and corneal fluorescein staining. The expression of IL-1β and TNF-α on the ocular surface and in lacrimal glands were analyzed by real-time PCR and western blot on the 14th day. The expression of Mucin-5 subtype AC (MUC5AC) was detected by Immunofluorescence staining in conjunctival tissue. The SCOP-treated rabbits exhibited significantly decreased aqueous tear secretion and increased corneal fluorescein staining scores over time. Both the mRNA expression levels and the protein expression levels of IL-1β and TNF-α were significantly increased after SCOP treatment compared with those after saline treatment. The loss of conjunctival MUC5AC was found in the SCOP-injected rabbits. Some infiltrated inflammatory cells and atrophic acinar cells were observed in the lacrimal gland after SCOP treatment. The disordered structures of the ocular surface and lacrimal glands were also observed. This study showed that repeated subcutaneous SCOP injections successfully elicited some of the typical dry eye symptoms commonly seen in humans. [ABSTRACT FROM AUTHOR]

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]

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 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders. [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]

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]

BACKGROUND: Our objective in this study was to evaluate the effectiveness of oligosaccharides extracted from black ginseng (OSBG), innovatively prepared by a low‐temperature steam‐heating process, in the improvement of learning and memory impairment in mice, as well as the mechanism(s). RESULTS: Eight carbohydrates involving isomaltose and maltotetraose were detected in black gensing; monosaccharide residues including mannose and rhamnose were also discovered. OSBG‐treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine group. OSBG could decrease acetylcholinesterase activity in a tissue‐dependent fashion but not in a dose‐dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase, glutathione, glutathione peroxidase (GPx), and Kelch‐like ECH‐associated protein 1, downregulation of malondialdehyde and nuclear factor erythroid 2‐related factor 2 in the tissues. Finally, at the genus level, we observed that the OSBG interventions increased the relative abundance of probiotics (e.g., Barnesiella, Staphylococcus, Clostridium_XlVb) and decreased pernicious bacteria such as Eisenbergiella and Intestinimonas, compared to the Alzheimer's disease mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine‐induced intestinal microbiota in mice, providing homeostasis of gut microbiota and providing evidence for microbiota‐regulated therapeutic potential. CONCLUSION: Our results showed for the first time a clear role for OSBG in improving scopolamine‐induced memory impairment by inhibiting cholinergic dysfunction in a tissue‐dependent manner. Additionally, OSBG administration relieved oxidative stress by activating the Keap‐1/Nrf2 pathway and modulating the gut microbiota. Collectively, OSBG may be a promising target for neuroprotective antioxidants for improving memory and cognition in Alzheimer's disease patients. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cognitive impairment (CI) is a significant public health concern, and bioactive peptides have shown potential as therapeutic agents. However, information about their synergistic effects on cognitive function is still limited. Here, we investigated the synergistic effects of tilapia head protein hydrolysate (THPH) and walnut protein hydrolysate (WPH) in mitigating CI induced by scopolamine in mice. RESULTS: The results showed that the combined supplementation of THPH and WPH (mass ratio, 1:1) was superior to either individual supplement in enhancing spatial memory and object recognition abilities in CI mice, and significantly lessened brain injury in CI mice by alleviating neuronal damage, reducing oxidative stress and stabilizing the cholinergic system. In addition, the combined supplementation was found to be more conducive to remodeling the gut microbiota structure in CI mice by not only remarkably reducing the ratio of Firmicutes to Bacteroidota, but also specifically enriching the genus Roseburia. On the other hand, the combined supplementation regulated the disorders of sphingolipid and amino acid metabolism in CI mice, particularly upregulating glutathione and histidine metabolism, and displayed a stronger ability to increase the expression of genes and proteins related to the brain‐derived neurotrophic factor (BDNF)/TrkB/CrEB signaling pathway in the brain. CONCLUSION: These findings demonstrate that tilapia head and walnut‐derived protein hydrolysates exerted synergistic effects in ameliorating CI, which was achieved through modulation of gut microbiota, serum metabolic pathways and BDNF signaling pathways. © 2024 Society of Chemical Industry. [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]

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 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.

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 method was developed for the determination of tropane alkaloids (TAs), including atropine, scopolamine, anisodamine and homatropine in buckwheat and related products. This work presents an optimised methodology based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction procedure followed by ultra-high performance liquid chromatography combined with time-of-flight mass spectrometry for the determination of TAs (atropine, scopolamine, anisodamine and homatropine) in buckwheat samples. The analytical methodology was successfully validated, demonstrating good linearity, low limit of quantification, repeatability (RSDr < 15%), inter-day precision (RSDR < 19%) and recovery (74–113%). Finally, 13 commercial samples of buckwheat were analysed and the results demonstrated that they were in compliance with the current European regulations regarding TAs. [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]

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]

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]

Scopolamine and atropine are two medicinal alkaloids derived from Datura stramonium L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth regulator, affects the biosynthesis and accumulation of these alkaloids in different plant tissues. The expression levels of putrescine N-methyltransferase (PMT), tropinone reductase I (TR1), and hyoscyamine 6β-hydroxylase (h6h), three critical enzymes in the biosynthetic pathway, were also analyzed. The results indicated that MJ at 150 µM increased the production of scopolamine and atropine in both leaves and roots, while MJ at 300 µM had an adverse effect. Furthermore, MJ enhanced the expression of PMT, TR1, and h6h genes in the roots, the primary site of alkaloid synthesis, but not in the leaves, the primary site of alkaloid storage. These results imply that MJ can be applied to regulate the biosynthesis and accumulation of scopolamine and atropine in D. stramonium, thereby improving their production efficiency. [ABSTRACT FROM AUTHOR]

Species of the genus Psychotria are used in popular medicine for pain, inflammatory symptoms, and mental disorders. Psychotria capillacea (Müll. Arg.) Standl. (Rubiaceae) is commonly known as coffee and some scientific studies have demonstrated its therapeutic potential. The goal of this study was to investigate the anti-inflammatory and neuroprotective effects, and acetylcholinesterase (AChE) inhibitory activity of a methanolic extract obtained from leaves of P. capillacea (MEPC), as well as the micromorphology and histochemistry of the leaves and stems of this plant. In addition, the MEPC was analyzed by UHPLC-MS/MS and the alkaloidal fraction (AF) obtained from the MEPC was tested in a mouse model of inflammation. MEPC contained three indole alkaloids, one sesquiterpene (megastigmane-type) and two terpene lactones. MEPC (3, 30 and 100 mg/kg) and AF (3 and 30 mg/kg) were evaluated in inflammation models and significantly inhibited edema at 2 h and 4 h, mechanical hyperalgesia after 4 h and the response to cold 3 h and 4 h after carrageenan injection. Scopolamine significantly increased the escape latency, and reduced the swimming time and number of crossings in the target quadrant and distance, while MEPC (3, 30 and 100 mg/kg), due to its neuroprotective actions, reversed these effects. AChE activity was significantly decreased in the cerebral cortex (52 ± 3%) and hippocampus (60 ± 3%), after MEPC administration. Moreover, micromorphological and histochemical information was presented, to aid in species identification and quality control of P. capillacea. The results of this study demonstrated that P. capillacea is an anti-inflammatory and antihyperalgesic agent that can treat acute disease and enhance memory functions in mouse models. [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]

Rationale: The rat cognitive effort task (rCET), a rodent model of cognitive rather than physical effort, requires animals to choose between an easy or hard visuospatial discrimination, with a correct hard choice more highly rewarded. Like in humans, there is stable individual variation in choice behavior. In previous reports, animals were divided into two groups—workers and slackers—based on their mean preference for the harder option. Although these groups differed in their response to pharmacological challenges, the rationale for using this criterion for grouping was not robust. Methods: We collated experimental data from multiple cohorts of male and female rats performing the rCET and used a model-based framework combining drift diffusion modeling with cluster analysis to identify the decision-making processes underlying variation in choice behavior. Results: We verified that workers and slackers are statistically different groups but also found distinct intra-group profiles. These subgroups exhibited dissociable performance during the attentional phase, linked to distinct decision-making profiles during choice. Reanalysis of previous pharmacology data using this model-based framework showed that serotonergic drug effects were explained by changes in decision boundaries and non-decision times, while scopolamine's effects were driven by changes in decision starting points and rates of evidence accumulation. Conclusions: Modeling revealed the decision-making processes that are associated with cognitive effort costs, and how these differ across individuals. Reanalysis of drug data provided insight into the mechanisms through which different neurotransmitter systems impact cognitively effortful attention and decision-making processes, with relevance to multiple psychiatric disorders. [ABSTRACT FROM AUTHOR]

Rich in unsaturated fatty acids, walnut oil provides a number of physiological benefits, including a reduction in the risk of cardiovascular disease and a delay in the aging process. In this work, walnut oil was prepared using the aqueous enzyme process and cold pressing method, and it was then analyzed using HPLC and FTIR. The characterization results show that the walnut oil extracted by the aqueous enzyme method outperformed the pressing oil in content of LLL by 11.64%, LLLn by 9.16% and OLL by 4.08%. But this oil had significantly less OLnLn (‐) than the pressing oil (7.90%). The Morris water maze and shuttle box tests of ICR mice revealed a notable improvement in the memory of the animals administered walnut oil. Among them, mice fed the walnut oil extracted by aqueous enzyme method showed a much shorter escape latency and a significantly higher rate of active avoidance reaction (p < 0.05, p < 0.01) than mice fed cold pressing method. With the prolongation of time, the mice even performed better than the positive control PIR group in all aspects. In summary, the quality of walnut oil extracted by aqueous enzyme method is better than that by cold pressing method. Practical Applications: Walnut oil prepared by aqueous enzymatic extraction can improve learning ability, is healthy and pollution‐free, and can be utilized as a dietary supplement in ordinary life. [ABSTRACT FROM AUTHOR]

LA or (±)-α-Lipoic acid (6,8-thioctic acid, 5-(1,2-dithiolan-3-yl)pentanoic acid) (LA) is a heterocyclic thia fatty acid consisting of pentanoic acid and a 1,2-dithiolan-3-yl group at the 5-position. LA is an amphiphilic pharmacophore with excellent antioxidant, anti-inflammatory and neuroprotective effects attested by numerous studies for its potential utility in both the treatment and diverse forms of prophylaxis of neurodegenerative disorders, especially Alzheimer's disease. This article aims to assess the differences in neuroprotective effect after short-term (11 days) and longterm (51 days) LA administration in an experimental rat model of scopolamine-induced dementia by correlating biochemical data on acetylcholinesterase activity with behavioural data. Behaviourally appraised changes in learning and memory appear to correlate with biochemical changes in AChE activity. The neuroprotective effect of LA, as ascertained by its beneficial effects on learning and memory in a scopolamine animal model, appears to be associated with cholinergic mechanisms (a decrease in AChE activity), and to be larger after short-term administration rather than long-term administration. These results further underscore the candidacy of LA as a viable drug candidate suitable for continued investigation and derivate synthesis endeavours. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain‐derived neurotrophic factor (BDNF) levels in the extracted brain tissues. Methods: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 μL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. Results: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically ‐citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active‐state human M1 mAChR and anchored here chiefly by hydrogen‐bonding and alkyl–π interactions. Conclusion: Our findings offer a solid experimental foundation for future RDEO‐based medicinal product development for patients suffering from AD. [ABSTRACT FROM AUTHOR]

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In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system. Scopolamine injection increases dopamine by inhibiting M2/4 muscarinic autoreceptors. These autoreceptors are located on dopaminergic presynaptic neurons, and their activation reduces the release of dopamine. Therefore, blocking these autoreceptors by scopolamine can increase the release of dopamine. Both D1 and D2 receptors are involved in learning and memory processes. In general, stimulation of dopamine D1 receptors follows an inverted U-shaped dose-response curve, meaning that both insufficient and excessive amounts of dopamine cause memory impairment. Therefore, an indirect effect on the dopaminergic system can be one of the scopolamine-induced memory impairment mechanisms. Effects on cell membrane potential and neuron plasticity, and interaction with acetylcholine are among other mechanisms. Serotonin plays a complex role in memory and learning. Serotonin receptors (5-HT2A) also play a role in memory function by affecting calcium transport. This action is similar to dopamine and other G-protein-coupled receptors, which activate phospholipase C, enter calcium into the cell, and activate calcineurin. Activation of 5-HT2A and 5-HT4 receptors by specific agonists of these receptors enhances long-term potentiation (LTP), which plays a significant role in memory. On the other hand, specific 5-HT3 receptor antagonist improves LTP. The 5-HT6 receptor antagonist can improve memory function. Therefore, different serotonin receptors have different roles in memory function, and the interaction between scopolamine and these receptors needs further study. It has been shown that histamine increases the secretion of acetylcholine in the hippocampus, and postsynaptic H1 and presynaptic H3 receptors play a major role in memory and learning; however, whether scopolamine can cause memory impairment through interaction with histamine receptors has been not reviewed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is associated with cognitive deficits and epigenetic deacetylation that can be modulated by natural products. The role of natural oxyresveratrol-β-cyclodextrin (ORV) on cognition and histone deacetylase activity in AD is unclear. Herein, in-silico docking and molecular dynamics simulation analysis determined that oxyresveratrol potentially targets histone deacetylase-2 (HDAC2). We therefore evaluated the in vivo ameliorative effect of ORV against cognitive deficit, cerebral and hippocampal expression of HDAC in experimental AD rats. Intracerebroventricular injection of STZ (3 mg/kg) induced experimental AD and the rats were treated with low dose (200 mg/kg), high dose (400 mg/kg) of ORV and donepezil (10 mg/kg) for 21 days. The STZ-induced AD caused cognitive and behavioural deficits demonstrated by considerable increases in acetylcholinesterase activity and escape latency compared to sham control. The levels of malondialdehyde (MDA) and HDAC activity were significantly increased in AD disease group comparison to the sham. Interestingly, the ORV reversed the cognitive-behavioural deficit and prominently reduced the MDA and HDAC levels comparable to the effect of the standard drug, donepezil. The findings suggest anti-AD role of ORV via antioxidant effect and inhibition of HDAC in the hippocampal and frontal cortical area of rats for AD. [ABSTRACT FROM AUTHOR]

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

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

This article explores the potential therapeutic benefits of naringin, a compound found in citrus fruits, for individuals with Alzheimer's disease (AD). The study used an animal model of AD to investigate the effects of naringin on memory impairment, the volume of a specific area in the brain called the CA1 area, and neuronal loss. The results indicated that naringin improved memory, increased the volume of the CA1 area, and increased the number and density of neurons in the hippocampus. The study suggests that naringin could be a promising treatment for memory deficits and neuronal loss in AD. [Extracted from the article]

Many people around the world suffer from neurodegenerative diseases associated with cognitive impairment. As life expectancy increases, this number is steadily rising. Therefore, it is extremely important to search for new treatment strategies and to discover new substances with potential neuroprotective and/or cognition-enhancing effects. This study focuses on investigating the potential of astragaloside IV (AIV), a triterpenoid saponin with proven acetylcholinesterase (AChE)-inhibiting activity naturally occurring in the root of Astragalus mongholicus, to attenuate memory impairment. Scopolamine (SCOP), an antagonist of muscarinic cholinergic receptors, and lipopolysaccharide (LPS), a trigger of neuroinflammation, were used to impair memory processes in the passive avoidance (PA) test in mice. This memory impairment in SCOP-treated mice was attenuated by prior intraperitoneal (ip) administration of AIV at a dose of 25 mg/kg. The attenuation of memory impairment by LPS was not observed. It can therefore be assumed that AIV does not reverse memory impairment by anti-inflammatory mechanisms, although this needs to be further verified. All doses of AIV tested did not affect baseline locomotor activity in mice. In the post mortem analysis by mass spectrometry of the body tissue of the mice, the highest content of AIV was found in the kidneys, then in the spleen and liver, and the lowest in the brain. [ABSTRACT FROM AUTHOR]