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Inadequate levels of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been reported as a risk factor for neurodegenerative diseases, including Alzheimer's disease. Avocado oil (Persea americana Mill., Laucaceae) represents a source of bioactive compounds with a relative abundance of omega-3, omega-6 polyunsaturated, and omega-9 monounsaturated fatty acids. The present study investigated the effects of extra-virgin avocado oil on the D-galactose-induced Alzheimer's disease model in ovariectomized Wistar rats. The cognitive dysfunctions were induced by D-galactose administration (150 mg.kg−1 i.p) and/or ovariectomy in 54 female rats for 70 days. The rats were concomitantly treated with extra-virgin avocado oil (0.25, 0.5, and 1 mL.kg−1, p.o), donepezil (1 mg.kg−1, p.o), and estradiol valerate (1 mg.kg−1, p.o). Memory disorders were evaluated using the Object Recognition, Y-Maze, and Morris water maze tests. Some biochemical and histological parameters regarding memory function were evaluated on hippocampus homogenate and tissue. D-galactose administration and ovariectomy significantly induced learning and memory impairments, decreased relative hippocampal weight (p < 0.001), the levels of acetylcholine (p < 0.001), glutamate (p < 0.001), reduced glutathione (p < 0.001), catalase (p < 0.05), and superoxide dismutase (p < 0.001) activities, and an increase (p < 0.001) in the levels of methylglyoxal, malondialdehyde, and nitrites. The treatment with extra-virgin avocado oil at all tested doses reversed or prevented the negative effects induced by ovariectomy and/or by D-galactose. Taken together, these results suggest that avocado oil possesses neuroprotective properties and can be consumed or supplemented to prevent the onset of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • EEPF inhibits Aβ aggregation and displays strong antioxidant activity. • EEPF improves memory impairment via targeting neuronal death and inflammation. • Neuroprotective action of EEPF is modulated through CaMK2/FER signaling pathway. • Anti-inflammatory effect of EEPF is regulated through Smad3/cyclin D3 pathway. Alzheimer's disease (AD) is the most common cause of dementia and is caused by various factors including amyloid-beta (Aβ) aggregation. We investigated the pharmacological effects of the ethanol extract of Potentilla fragarioides var. major (Rosaceae) (EEPF) on AD-related pathogenesis, which remain elusive. We observed the effects of EEPF on Aβ disaggregation and free-radical scavenging activities for 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) using in vitro assays, evaluated the effects of EEPF on memory loss in two animal models, and examined the molecular regulatory mechanisms of EEPF using an antibody-protein microarray in EEPF-treated neuronal cell lines. EEPF inhibited Aβ aggregation in a concentration-dependent manner and enhanced free-radical scavenging activities for ABTS and DPPH. EEPF significantly inhibited memory impairment in the passive avoidance task, Y-maze test, and Morris water maze test in scopolamine-induced short-term memory loss mice and Aβ-injected AD-like mice. Nissl staining and immunohistochemistry for NeuN and Iba-1 confirmed the neuroprotective and anti-inflammatory effects of EEPF in both animal models. In H 2 O 2 -treated HT22 hippocampal cells, EEPF significantly prevented cell damage, enhanced CaMK2, and reduced ferric reductase. In lipopolysaccharide (LPS)-stimulated BV-2 microglia, EEPF significantly inhibited LPS-induced production of inflammatory factors, such as nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-6, and decreased the phosphorylation of Smad3 and cyclin D3. High-performance liquid chromatography confirmed that EEPF has five major components: neochlorogenic acid, chlorogenic acid, polydatin, isochlorogenic acid A, and buddleoside, with amounts ranging across 1.91–9.41 mg/g. EEPF may be a promising drug for treatment of AD and AD-related brain disorders. [ABSTRACT FROM AUTHOR]

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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]

Introduction Methods Results Conclusions Carotid sinus syndrome (CSS), characterized by exaggerated vagal responses leading to asystolic pauses with carotid sinus massage (CSM), often necessitates pacemaker implantation. This study investigates cardioneuroablation (CNA) as an alternative strategy for CSS.Prospective study of consecutive patients referred for CNA due to CSS. All patients underwent CSM, atropine test and 24‐h Holter monitoring before the procedure and at 6 months. The primary objective was the absence of any cardioinhibitory response to CSM following CNA. Secondary objectives included the combined endpoint of syncope and presyncope‐free survival, pacemaker‐free survival, differences in heart rate variation (HRV), as well as differences in the pre‐ and postprocedure atropine tests and in the SF‐36 quality‐of‐life questionnaire.A total of 13 consecutive patients (84.6% male, mean age 63.8 ± 12.3 years) were included. CSM revealed a symptomatic asystolic pause in all patients before CNA (7.3 [5.6–10.5] s). After the procedure, all the patients had a negative CSM, and only one patient (7.7%) had a positive CSM at 6 months. After a median follow‐up of 11.2 (10.6–16.3) months, syncope or presyncope‐free survival was 84.6%, and none required pacemaker implantation. There was an improvement in the energy and health change items in the SF‐36 questionnaire. There was a reduction in HR increase in the atropine test at 6 months (pre‐CNA: 66% [52–84] vs. post‐CNA 26.0% (19.8–29.3]; p = .008) and in HRV parameters.In this proof‐of‐efficacy study, performed in patients affected by asystolic CSS, CNA was effective in reducing the rate of cardioinhibitory responses, suggesting a potential efficacy in also reducing syncopal recurrences. Controlled trials are warranted to corroborate clinical findings. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease is a progressive neurodegenerative disease that causes an irreversible decline in the functional, cognitive, and behavioral activities of affected individuals. Amifostine is a cytoprotective drug with well-documented pleiotropic effects such as anti-inflammatory, antioxidant, and anti-apoptotic effects. The study was carried out to investigate the neuroprotective effect of amifostine in a mouse model of Alzheimer's disease. Methods: Swiss Webster albino mice were divided into four groups (n = 10): (I) control, (II) scopolamine (1 mg/kg i.p. once daily for 7 days), and two treatment groups. The treatment groups received the test drugs prophylactically for 2 weeks, followed by induction with scopolamine and the test drug at the same doses for one week, followed by (III) donepezil (5 mg/kg daily, i.p. for three weeks) or (IV) amifostine (200 mg/kg daily, i.p. for three weeks). After the treatments, behavioral tests were conducted using the spontaneous Y maze test and the novel object recognition test (NORT). The brain tissue homogenates of the experimental mice were processed for biological analysis. The levels of inflammatory (TNF-α, IL-6, and IL-1β), and oxidative stress (SOD and MDA) markers, as well as acetyl cholinesterase, were determined. Results: Scopolamine intraperitoneal administration resulted in impairment of cognitive performance and neurotoxicity. Amifostine significantly attenuated scopolamine-induced injury, as observed in improved spatial working memory. Moreover, amifostine significantly reduced lipid peroxidation, increased SOD level, and reduced the proinflammatory markers and acetyl cholinesterase activity in brain tissue homogenates. Conclusion: Preconditioning with amifostine had a neuroprotective effect, maintained cognitive function, and enhanced cholinergic activity in the scopolamine-induced mouse model of Alzheimer's disease. [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]

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]

This study looked at the amount of tropane alkaloids in both the leaves of the mother plant and the callus cultures of Hyoscyamus niger L. It also looked at how biotic elicitation affects the growth of callus cultures and increases the production of alkaloids. The investigation identified and quantified three primary tropane alkaloids (Hyoscyamine, Scopolamine, and Atropine) from both sources. Remarkably, the callus cultures exhibited obviously higher levels of alkaloids in comparison to the leaves of the mother plant, implying their potential as a valuable reservoir for alkaloid production. Concerning the effects of biotic elicitation, the study showed that the application of chitosan (CHT), yeast extract (YE), and fungal extract of Trichoderma asperellum yielded a substantial decrease in callus weight when contrasted with the control group. This decrease became more pronounced with escalating concentrations of the elicitors. In terms of alkaloid synthesis, a clear correlation between the concentration of bio stimulants and tropane alkaloid levels was established. Particularly, CHT elicitation displayed the most pronounced enhancement in levels of tropane alkaloids among the three elicitors. Notably, the highest CHT concentration of 40 mg/L yielded the most elevated levels of alkaloids, measuring at 25.3 µg/g for Hyoscyamine, 31.2 µg/g for Scopolamine, and 21.5 µg/g for Atropine. This represents approximate percentage increases in concentration of 208%, 183%, and 198%, respectively, when compared to the control treatment. Generally, these findings carry significant implications for advancing tropane alkaloid biosynthesis, with potential applications spanning the pharmaceutical and biotechnology sectors. [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]

Pearl oyster shells are composed of a double layer of calcium carbonate polymorphs: prismatic and nacreous. The nacreous layer is used in functional foods and cosmetics. In an earlier work, we reported that sulfated polysaccharides in nacre extract ameliorated memory impairment induced by a single dose of scopolamine. Here, we investigated whether sulfated polysaccharides suppress amyloid-beta (Aβ) deposition in an Alzheimer's disease model induced by prolonged administration of scopolamine. Chronic scopolamine administration induces Aβ deposition; however, sulfated polysaccharides suppressed this effect. Additionally, sulfated polysaccharides ameliorated the accumulation of phosphorylated tau, neuroinflammation, and neuronal cell death in the brain, which are common features of patients with Alzheimer's disease. To further determine the inhibitory mechanisms of Aβ deposition, we assessed the amount of the Aβ-degrading enzyme insulin-degrading enzyme (IDE). In animal experiments, sulfated polysaccharides increased IDE levels in scopolamine-treated mice. To study the effect of sulfated polysaccharides on insulin signaling, which regulates IDE expression, we evaluated the expression levels of phosphorylated Akt and nuclear factor-kB. Sulfated polysaccharides restored the levels of phosphorylated Akt and nuclear factor-kB, which were decreased and increased, respectively, using scopolamine treatment. Overall, our findings suggest that sulfated polysaccharides suppress Aβ deposition by regulating IDE expression. [ABSTRACT FROM AUTHOR]

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

• Dapagliflozin enhances the Nrf2 pathway and increases IGF-1, IGFBP-3, and BDNF levels in a rat ASD model. • Treatment reduces TNF-α, IL-17, and MDA levels, demonstrating anti-inflammatory properties. • Dapagliflozin improves cognitive and memory functions in PPA-induced ASD. • Modulates apoptotic mechanisms, suggesting therapeutic potential for oxidative stress and inflammation-related ASD. • Further studies needed to explore additional pathways and validate clinical potential. The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder. [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]

The prevalence of sexual dysfunction is high in mental illness-related diseases. This study seeks to assess the sexual-enhancing properties of Alchornea cordifolia and Lecaniodiscus cupanioides-supplemented diets in scopolamine-administered rats (SIA). The experimental design consists of 7 groups designated as Group 1: Healthy rats; Group 2: SIA (untreated); Group 3: SIA rats treated with tadalafil; Groups 4 and 5: SIA rats fed with diet supplemented with Alchornea cordifolia (10 and 20% inclusion) and Groups 6 and 7: SIA rats fed with diet supplemented with Lecaniodiscus cupanioides (10 and 20% inclusion). The rats were pre-treated with the supplemented diets; the rats were administered scopolamine (3 mg/kg body weight) on the 12th day of the experiment, and the sexual behavioural study was evaluated on the 14th day of the experiment. After that, the rats were sacrificed, penile tissue was removed and homogenised, and obtained homogenate was used for biochemical evaluations. The obtained results revealed that untreated SIA rats exhibited significantly lower sexual ability when compared with healthy and diet-treated SIA rats. Also, the untreated SIA rats had higher activity of phosphodiesterase-5, angiotensin-1-converting enzyme, arginase, acetylcholinesterase, reduced nitric oxide level and lower antioxidant status in penile tissue when compared with healthy rats and SIA rats pre-treated with the formulated diets, respectively. The sexual ability was enhanced, and the activity of key enzymes linked to erectile dysfunction was reduced in treated SIA rats. Lecaniodiscus cupanioide-supplemented diets promoted sexual ability higher than Alchornea cordifolia-supplemented diets when comparing their overall effects. [ABSTRACT FROM AUTHOR]

This study investigated the neuroprotective effect of 70% ethanol extract of Ecklonia cava (EE) in amyloid beta (Aβ)-induced cognitive deficit mice. As a result of analyzing the bioactive compounds in EE, nine compounds were identified using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In particular, the diekcol content was quantified by high-performance liquid chromatography with diode-array detection (DAD-HPLC). Biochemical analysis was performed on brain tissue to determine the mechanism of the cognitive function improvement effect of EE. The result showed that EE ameliorated learning and memory decline in behavioral tests on Aβ-induced mice. EE also attenuated oxidative stress by regulating malondialdehyde (MDA) content, reduced glutathione (GSH), and superoxide dismutase (SOD) levels. Similarly, EE also improved mitochondrial dysfunction as mitochondrial membrane potential, ATP production, and reactive oxygen species (ROS) levels. In addition, EE enhanced synapse function by modulating acetylcholine-related enzymes and synaptic structural proteins in the whole brain, hippocampus, and cerebral cortex tissues. Also, EE regulated Aβ-induced apoptosis and inflammation through the c-Jun N-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, EE protected neurotoxicity by increasing brain-derived neurotrophic factor (BDNF) production. These results suggest that EE may be used as a dietary supplement for the prevention and treatment of Alzheimer's disease (AD). [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: Surgery such as ovariectomy causes an inflammatory and oxidative stress. This study was designed to evaluate endogenous tocopherol levels in response to surgical oxidative stress induced by abdominal surgery (ovariectomy) in thirty-two juvenile female dogs. The dogs received meloxicam before surgery (0.2 mg/kg SC) and after surgery (0.1 mg/kg OS every 24 h), 0.03 mg/kg of atropine sulfate (IM), and propofol 4 mg/kg intravenously (IV). General anesthesia was maintained with sevoflurane. Physiological, hematological and biochemical parameters, malondialdehyde (MDA) and α-, δ-, γ-tocopherols were evaluated at baseline, 36 and 48 h after surgery. Results: The physiological parameters remained within normal ranges. Blood glucose concentration increased, while the albumin levels decreased after surgery. Rescue analgesia was not required. MDA levels increased above the baseline at 36 and 48 h after surgery (P < 0.001). The α-, δ-, and γ-tocopherol concentrations decreased from baseline at 36 and 48 h after surgery (P < 0.001). Conclusions: Surgery in juvenile female dogs revealed oxidative, increased MDA concentrations, reduced tocopherol levels, and had a clinically insignificant influence on homeostasis. [ABSTRACT FROM AUTHOR]

Background: Hippeastrum reticulatum (HR) belongs to the Amaryllidaceae, a well-known ornamental family. Objectives: This study was designed to reveal in vivo anti-acetylcholinesterase (AChE) and antioxidant activities and evaluate the acute toxicity of the alkaloid fraction (AF). Methods: The D-galactose-induced aging model and the scopolamine-induced cognitive-deficit model were used for the in vivo tests. The median lethal dose (LD50) of the AF was determined using the Litchfield and Wilcoxon method. Results: On the aging model, the AF at 10 and 15 mg/kg significantly improved the antioxidant markers including superoxide dismutase, glutathione peroxidase, and malonyl dialdehyde. Upon the scopolamine-injected mice, the AF at 10 and 15 mg/kg notably downregulated cerebral AChE in mice. The LD50 of the HR AF is 90.2 mg/kg. Conclusion: These findings provide strong evidence for the safety and advantages of utilizing HR in treating Alzheimer's disease. [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]

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]

Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system and particularly in the formation of amyloid plaques; therefore, the inhibition of AChE has become one of the most promising strategies for the treatment of AD, particularly concerning AChE inhibitors that interact with the peripheral anionic site (PAS). Ceanothic acid isolated from the Chilean Rhamnaceae plants is an inhibitor of AChE through its interaction with PAS. In this study, six ceanothic acid derivatives were prepared, and all showed inhibitory activity against AChE. The structural modifications were performed starting from ceanothic acid by application of simple synthetic routes: esterification, reduction, and oxidation. AChE activity was determined by the Ellmann method for all compounds. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compounds would be produced by interaction with the PAS of AChE. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the ceanothane derivatives were performed using the Swiss ADME tool. [ABSTRACT FROM AUTHOR]

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be −4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD. [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]

Background: Animal intubation is necessary in painful surgery procedures in order to maintain general anaesthesia and analgesia. In swine, orotracheal intubation is difficult or impossible; all possible measures to improve it need to be explored. Methods: Two groups of a total of 20 clinically healthy local mixed breed (Sus scrofa domesticus) premedicated swine underwent intubation. The animals were randomly divided into two groups, one using atropine sulphate (A) and one using saline solution (N), prior to endotracheal intubation. Premedication started with intramuscular injection of xylazine, ketamine and fentanyl. Intubation was performed after induction with thiopental sodium administered intravenously with atropine sulphate or saline solution. Larynxes were photographed and filmed and coded images and videos were sent to investigators for evaluation. Result: In this study, a negative effect of atropine sulphate on the laryngeal visibility, opening and accessibility in local mixed breed anesthetized pigs was identified. [ABSTRACT FROM AUTHOR]

Methylene blue (MB) has a long story of use and has been employed for various diseases, however, most of its current rekindled research is related to its function in the mitochondria. MB is gaining interest as a possible treatment because mitochondrial dysfunction is an apparent unifying pathogenic characteristic of a variety of neurodegenerative conditions. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by impairment of cognitive functions. This study aims to investigate whether MB treatment improves impaired cognitive functions and reduces hippocampal amyloid-β levels and oxidative stress in a D-galactose-induced AD mouse model. Twenty-four wild-type Balb/c mice were randomly divided into four groups (control, D-galactose-induced AD, MB-treated AD, and only MB-treated mice). Mice in the corresponding groups were injected with D-galactose (50 mg/kg, s.c.) for 60 days. In the MB treatment groups, the mice were treated with MB (2 mg/kg, orally) for the last 14 days of treatments. The Morris water maze test was used to assess spatial learning and memory functions. Amyloid β-42, malondialdehyde, superoxide dismutase, and nitric oxide levels in the hippocampi of mice were measured using ELISA and spectrophotometry. MB treatment improved impaired learning and memory functions induced by D-galactose administration and decreased amyloid β-42 concentration in the hippocampi of mice. Malondialdehyde level was found to decrease in MB-treated mice compared to D-galactose-induced AD mice in the hippocampus and plasma. The hippocampus of MB-treated mice displayed increased superoxide dismutase activity while decreased nitric oxide concentration compared to the ones of D-galactose-induced AD mice. MB has been shown to improve learning and memory impairments, as well as reduce Aβ-42 concentration and oxidative stress in the hippocampus of D-galactose-induced AD mice. The findings of this study demonstrate that MB may offer potential benefits as a repurposed agent for AD. [ABSTRACT FROM AUTHOR]

Fluorotelomer alcohols are an alternative to neurotoxic perfluoroalkyl carboxylic acids, a sub-class of per- and poly-fluoroalkyl substances (PFAS). However, the effect of the fluorotelomer alcohol in offspring is poorly known. Here pregnant mice were exposed to various doses of the 6:2 fluorotelomer alcohol through intragastric administration from gestation day 8.5 until delivery. Results show that the fluorotelomer alcohol impaired the development of the blood–brain barrier and altered brain immune microenvironment, causing anxiety-like behavior and impairments in learning memory. Mechanistic studies suggest that this is due to the activation of the serine and threonine kinase AKT/nuclear factor kappa-b/matrix metalloproteinases signaling pathway, resulting in the degradation of the tight junction protein occludin, which in turn caused disruption of endothelial barrier function. Our findings represent the first evidence that gestational exposure to the 6:2 fluorotelomer alcohol causes neurotoxicity in offspring. [ABSTRACT FROM AUTHOR]

An analytical method for the simultaneous quantification of neurotransmitters has been developed using reversed-phase ion-pair high performance liquid chromatography (RPIP-HPLC) coupled with electrochemical detection (ECD). As a strategy to simultaneously analyze acetylcholine, glutamate, and γ-aminobutyric acid, which were previously difficult to analyze in ECD, along with serotonin and dopamine, the ion pair separation technique was optimized, and electroactivity was induced by eluting with strong alkaline solution. This method achieved improved sensitivity, showing limits of quantification of 0.02 to 0.1 μg/mL and linear regression coefficients of determination of 0.9938–0.9994 through the use of an 8% acetonitrile solution containing 15 mM H3PO4 and 0.4 mM sodium 1-octanesulfonate as the mobile phase and 200 mM NaOH as the post-column eluent, detected at the gold electrode. All inter- and intra-day precision were below 4.10%, and the average recoveries were 97.43–103.69%. In an application comparing cerebral cortical tissues and hippocampal tissues between a control group and a scopolamine-treated group, the levels of the five components showed a clear difference. As a result of evaluating the eco-friendliness of this method, the Analytical GREEnness metric was determined as 0.47. Our method is expected to be useful in screening for neurotransmitters in various biological and clinical samples. [ABSTRACT FROM AUTHOR]

Atropine eye drops have been shown to slow the progression of myopia, but there has been limited research on the effectiveness of 0.05% atropine in treating myopia. This study aimed to investigate the safety and efficacy of 0.05% atropine eye drops in controlling myopia in children. The study included 424 participants aged 6 to 12 years between January 1, 2015, and January 1, 2021. Of these, 213 were randomly assigned to the 0.05% atropine group and 211 to the placebo group. The cycloplegic spherical equivalent (SE), axial length (AL), corneal curvature (K), and anterior chamber depth (ACD) were measured using IOLMaster. The lens power and corneal astigmatism were also determined. The changes in ocular biometric parameters were compared between the two groups, and the contributions of ocular characteristics to SE progression were calculated and compared. Over a 12-month period, the changes in spherical equivalent were −0.03 ± 0.28 and −0.32 ± 0.14 in the atropine and placebo groups, respectively (P =.01). The changes in axial length were 0.06 ± 0.11 and 0.17 ± 0.12, respectively (P =.01). At 18 and 24 months, there were significant differences in axial length and spherical equivalent between the atropine and placebo groups. Multiple regression models accounting for changes in AL, K, and lens magnification explained 87.23% and 98.32% of SE changes in the atropine and placebo groups, respectively. At 1 year (p =.01) and 2 years (p =.03), there were significant differences in photophobia between the atropine and placebo groups. This two-year follow-up study demonstrates that 0.05% atropine eye drops are safe and effective in preventing the development of myopia in school-aged children. [ABSTRACT FROM AUTHOR]

The morbidity and mortality associated with type 2 diabetes mellitus (T2DM) have grown exponentially over the last 30 years. Together with its associated complications, the mortality rates have increased. One important complication in those living with T2DM is the acceleration of age‐related cognitive decline. T2DM‐induced cognitive impairment seriously affects memory, executive function, and quality of life. However, there is a lack of effective treatment for both diabetes and cognitive decline. Thus, finding novel treatments which are cheap, effective in both diabetes and cognitive impairment, are easily accessible, are needed to reduce impact on patients with diabetes and health‐care systems. Carnosine, a histidine containing dipeptide, plays a protective role in cognitive diseases due to its antioxidant, anti‐inflammation, and anti‐glycation properties, all of which may slow the development of neurodegenerative diseases and ischemic injury. Furthermore, carnosine is also involved in regulating glucose and insulin in diabetes. Herein, we discuss the neuroprotective role of carnosine and its mechanisms in T2DM‐induced cognitive impairment, which may provide a theoretical basis and evidence base to evaluate whether carnosine has therapeutic effects in alleviating cognitive dysfunction in T2DM patients. [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]

Substance abuse among adolescents has become a growing issue throughout the world. The significance of research on this life period is based on the occurrence of neurobiological changes in adolescent brain which makes the individual more susceptible for risk-taking and impulsive behaviors. Alcohol and nicotine are among the most available drugs of abuse in adolescents. Prolonged consumption of nicotine and alcohol leads to drug dependence and withdrawal which induce various dysfunctions such as memory loss. Coenzyme Q10 (CoQ10) is known to improve learning and memory deficits induced by various pathological conditions such as Diabetes mellitus and Alzheimer's disease. In the present study we investigated whether CoQ10 treatment ameliorates memory loss following a nicotine-ethanol abstinence. Morris water maze and novel object recognition tests were done in male Wistar rats undergone nicotine-ethanol abstinence and the effect of CoQ10 was assessed on at behavioral and biochemical levels. Results indicated that nicotine-ethanol abstinence induces memory dysfunction which is associated with increased oxidative and inflammatory response, reduced cholinergic and neurotrophic function plus elevated Amyloid-B levels in hippocampi. CoQ10 treatment prevented memory deficits and biochemical alterations. Interestingly, this ameliorative effect of CoQ10 was found to be dose-dependent in most experiments and almost equipotential to that of bupropion and naloxone co-administration. CoQ10 treatment could effectively improve memory defects induced by nicotine-ethanol consumption through attenuation of oxidative damage, inflammation, amyloid-B level and enhancement of cholinergic and neurotrophic drive. Further studies are required to assess the unknown side effects and high dose tolerability of the drug in human subjects. [ABSTRACT FROM AUTHOR]

Background and aim: Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats. Experimental procedure: The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level. Result: Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group. Conclusions: Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms. [ABSTRACT FROM AUTHOR]

Soybean vegetable oil is an important source of the human diet. However, the analysis of the genetic mechanism leading to changes in soybean oil content is still incomplete. In this study, a total of 227 soybean materials were applied and analyzed by a genome-wide association study (GWAS). There are 44 quantitative trait nucleotides (QTNs) that were identified as associated with oil content. A total of six, four, and 34 significant QTN loci were identified in Xiangyang, Hulan, and Acheng, respectively. Of those, 26 QTNs overlapped with or were near the known oil content quantitative trait locus (QTL), and 18 new QTNs related to oil content were identified. A total of 594 genes were located near the peak single nucleotide polymorphism (SNP) from three tested environments. These candidate genes exhibited significant enrichment in tropane, piperidine, and pyridine alkaloid biosynthesiss (ko00960), ABC transporters (ko02010), photosynthesis-antenna proteins (ko00196), and betalain biosynthesis (ko00965). Combined with the GWAS and weighted gene co-expression network analysis (WGCNA), four candidate genes (Glyma.18G300100, Glyma.11G221100, Glyma.13G343300, and Glyma.02G166100) that may regulate oil content were identified. In addition, Glyma.18G300100 was divided into two main haplotypes in the studied accessions. The oil content of haplotype 1 is significantly lower than that of haplotype 2. Our research findings provide a theoretical basis for improving the regulatory mechanism of soybean oil content. [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]

The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the rat cerebellum (centred on interpositus nucleus) and observed the motor effects through a battery of behavioural tests. These tests included unrewarded behaviour during open field exploration and a horizontal ladder walking task and reward‐based beam walking and pellet reaching tasks. Infusion of a mix of the antagonists did not impair motor learning in the horizontal ladder walking or the reaching task but reduced spontaneous movement during open field exploration, impaired coordination during beam walking and ladder walking, led to fewer reaches in the pellet reaching task, slowed goal‐directed reaching behaviour and reduced reward pellet consumption in a free access to food task. Infusion of the muscarinic antagonist scopolamine on its own resulted in deficits in motor performance and a reduction in the number of reward pellets consumed in the free access to food task. By contrast, infusion of the nicotinic antagonist mecamylamine on its own had no significant effect on any task, except beam walking traversal time, which was reduced. Together, these data suggest that acetylcholine in the cerebellar interpositus nucleus is important for the execution and coordination of voluntary movements mainly via muscarinic receptor signalling, especially in relation to reward‐related behaviour. [ABSTRACT FROM AUTHOR]

Vascular dementia (VD) is a degenerative cerebrovascular disorder associated with progressive cognitive decline. Previous reports have shown that 7,8-dihydroxyflavone (7,8-DHF), a well-known TrkB agonist, effectively ameliorates cognitive deficits in several disease models. Therefore, this study investigated the protective effects of 7,8-DHF against 2-VO-induced VD. VD was established in rats using the permanent bilateral carotid arteries occlusion (two-vessel occlusion, 2-VO) model. 7,8-DHF (5, 10, and 20 mg/kg) and Donepezil (10 mg/kg) were administered for 4 weeks. Memory function was assessed by the novel objective recognition task (NOR) and Morris water maze (MWM) tests. Inflammatory (TNF-α, IL-1β, and NF-kβ), oxidative stress, and apoptotic (BAX, BCL-2, caspase-3) markers, along with the activity of choline acetylcholinesterase (AChE) was assessed. p-AKT, p-CREB, BDNF, and neurotransmitter (NT) (GLU, GABA, and ACh) levels were also analyzed in the hippocampus of 2-VO rats. Our results show that 7,8-DHF effectively improved memory performance and cholinergic dysfunction in 2-VO model rats. Furthermore, 7,8-DHF treatment also increased p-AKT, p-CREB, and BDNF levels, suppressed oxidative, inflammatory, and apoptotic markers, and restored altered NT levels in the hippocampus. These findings imply that 7, 8-DHF may act via multiple mechanisms and as such serve as a promising neuroprotective agent in the context of VD. [ABSTRACT FROM AUTHOR]

Cognitive dysfunctions are now recognized as core symptoms of various psychiatric disorders e.g., major depressive disorder. Sustained immune activation may leads to cognitive dysfunctions. Proinflammatory cytokines shunt the metabolism of tryptophan towards kynurenine and quinolinic acid may accumulate at toxic concentrations. This acid triggers an increase in neuronal nitric oxide synthase function and promotes oxidative stress. The searching for small molecules that can regulate tryptophan metabolites produced in the kynurenic pathway has become an important goal in developing treatments for various central nervous system diseases with an inflammatory component. Previously we have identified a small hybrid molecule – MM165 which significantly reduces depressive-like symptoms caused by inflammation induced by lipopolysaccharide administration. In the present study, we investigated whether this compound would mitigate cognitive deficits induced by lipopolysaccharide administration and whether treatment with it would affect the plasma or brain levels of quinolinic acid and kynurenic acid. Neuroinflammation was induced in rats by administering lipopolysaccharide at a dose of 0.5 mg/kg body weight for 10 days. We conducted two tests: novel object recognition and object location, to assess the effect on memory impairment in animals previously treated with lipopolysaccharide. In plasma collected from rats, the concentrations of C-reactive protein and tumor necrosis factor alfa were determined. The concentrations of kynurenic acid and quinolinic acid were determined in plasma and homogenates obtained from the cerebral cortex of rats. Interleukin 6 in the cerebral cortex of rats was determined. Additionally, the body and spleen mass and spontaneous activity were measured in rats. Our study shows that MM165 may mitigate cognitive deficits induced by inflammation after administration of lipopolysaccharide and alter the concentrations of tryptophan metabolites in the brain. Compounds exhibiting a mechanism of action analogous to that of MM165 may serve as foundational structures for the development of a new class of antidepressants. [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]

Purpose: To assess over 2 weeks, the effect of 3 different low concentrations of atropine on pupillary diameter and accommodative amplitude in children with myopia. Methods: Fifty-eight children with myopia [spherical equivalent (SE) of −0.50 diopters (D) or worse, astigmatism of less than or equal to 2.00 D] were randomly allocated to 3 groups receiving 0.01%, 0.02%, or 0.03% atropine eye drops, once nightly for 2 weeks. The primary outcome was the change from baseline in pupillary diameter and accommodative amplitude with each of the concentrations. Results: Fifty-seven participants (114 eyes), aged between 6 and 12 years, completed the 2-week trial (mean age 9.3 ± 1.7 years and mean SE −3.53 ± 1.79 D). After 2 weeks of use, all the 3 concentrations were found to have a statistically significant effect on both the pupillary diameter and accommodative amplitude. Accommodative amplitude reduced by an average of 5.23 D, 9.28 D, and 9.32 D, and photopic pupil size increased by an average of 0.95 ± 1.05 mm, 1.65 ± 0.93 mm, and 2.16 ± 0.88 mm with 0.01%, 0.02%, and 0.03%, respectively. Of the eyes, a total of 5.3% and 5.9% of the eyes on 0.02% and 0.03% atropine had a mean residual accommodative amplitude of <5 D. The percentage of eyes having a pupillary dilation >3 mm were 4.8%, 10.5%, and 23.5% for 0.01%, 0.02%, and 0.03% atropine, respectively. Conclusions: Low-dose atropine had an effect on pupillary diameter and accommodative amplitude. With the highest concentration assessed, that is, 0.03% nearly 1 of 4 eyes had pupillary dilation of >3 mm. Clinical Trial Registration number: NCT03699423. [ABSTRACT FROM AUTHOR]

The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than Km. Thus, the bimolecular rate constant was found to be kcat/Km = 7.7 × 104 M−1 min−1. Rough estimates of catalytic parameters provided slow kcat < 40 min−1 and high Km = 0.3–3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug. [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]