Search

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]

This document contains abstracts from various scientific studies covering a range of topics in biology and related disciplines. The studies investigate maternal overnutrition and its potential link to liver disease and cancer in offspring, the inhibition of NLRP1 inflammasome activation for neuroprotection, the effects of a nicotinic intermediate on Alzheimer's disease, the use of artificial thymic organoids to study T-cell development, the inhibition of siderophore biosynthesis for Mycobacterium abscessus infections, machine learning for early prediction of ovarian cancer, transcriptomic study of nicotine catabolism, natural variation and cellular morphology patterns in epithelial cysts, new treatments for cell quiescence in acute myeloid leukemia, the impact of endocrine disruptors on cortical development, and more. These summaries provide a brief overview of the research findings and can serve as a starting point for library patrons conducting research in these areas. [Extracted from the article]

Copyright of Neurosciences is the property of Neurosciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss, imposing a significant burden on affected individuals and their families. Despite the recent promising progress in therapeutic approaches, more needs to be done to understand the intricate molecular mechanisms underlying the development and progression of AD. Growing evidence points to epigenetic changes as playing a pivotal role in the pathogenesis of the disease. The dynamic interplay between genetic and environmental factors influences the epigenetic landscape in AD, altering gene expression patterns associated with key pathological events associated with disease pathogenesis. To this end, epigenetic alterations not only impact the expression of genes implicated in AD pathogenesis but also contribute to the dysregulation of crucial cellular processes, including synaptic plasticity, neuroinflammation, and oxidative stress. Understanding the complex epigenetic mechanisms in AD provides new avenues for therapeutic interventions. This review comprehensively examines the role of DNA methylation and histone modifications in the context of AD. It aims to contribute to a deeper understanding of AD pathogenesis and facilitate the development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neuronal disorder that leads to the development of dementia. Until nowadays, some therapies may alleviate the symptoms, but there is no pharmacological treatment. Microdosing lithium has been used to modify the pathological characteristics of the disease, with effects in both experimental and clinical conditions. The present work aimed to analyze the effects of this treatment on spatial memory, anxiety, and molecular mechanisms related to long-term memory formation during the aging process of a mouse model of accelerated aging (SAMP-8). Female SAMP-8 showed learning and memory impairments together with disruption of memory mechanisms, neuronal loss, and increased density of senile plaques compared to their natural control strain, the senescence-accelerated mouse resistant (SAMR-1). Chronic treatment with lithium promoted memory maintenance, reduction in anxiety, and maintenance of proteins related to memory formation and neuronal density. The density of senile plaques was also reduced. An increase in the density of gamma-aminobutyric acid A (GABAA) and α7 nicotinic cholinergic receptors was also observed and related to neuroprotection and anxiety reduction. In addition, this microdose of lithium inhibited the activation of glycogen synthase kinase-3beta (GSK-3β), the classical mechanism of lithium cell effects, which could contribute to the preservation of the memory mechanism and reduction in senile plaque formation. This work shows that lithium effects in neuroprotection along the aging process are not related to a unique cellular mechanism but produce multiple effects that slowly protect the brain along the aging process. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide 1 (GLP-1) analogues have been commercialized for the management of type 2 diabetes. Recent studies have underscored GLP-1's role as a modulator of alcohol-related behavior. However, the role of the GLP-1 analogue liraglutide on alcohol-withdrawal responses have not been fully elucidated. Liraglutide binds to the G-protein-coupled receptor and activates an adenylyl cyclase and the associated classic growth factor signaling pathway, which acts growth factor-like and neuroprotective properties. The underlying neurobiological mechanisms of liraglutide on alcohol withdrawal remains unknown. This study endeavored to explore the effects of liraglutide on the emotion and memory ability of alcohol-withdrawal mice, and synaptic morphology in the medial prefrontal cortex (mPFC) and the hippocampus (HP), and thus affects the relapse-like drinking of alcohol-withdrawal mice. The alcohol-withdrawal group was reintroduced to a 20% v/v alcohol and water through the two-bottle choice for four consecutive days, a period referred to as alcohol re-drinking. Male C57BL/6J mice were exposed to a regimen of 20% alcohol and water for a duration of 6 weeks. This regimen established the two-bottle choice model of alcohol exposure. Learning capabilities, memory proficiency, and anxiety-like behavior were evaluated using the Morris water maze, open field, and elevated plus maze paradigms. Furthermore, synaptic morphology and the levels of synaptic transport-related proteins were assessed via Golgi staining and Western Blot analysis after a two-week alcohol deprivation period. Alcohol re-drinking of alcohol-withdrawal mice was also evaluated using a two-bottle choice paradigm. Our findings indicate that liraglutide can substantially decrease alcohol consumption and preference (p < 0.05) in the alcohol group and enhance learning and memory performance (p < 0.01), as well as alleviate anxiety-like behavior (p < 0.01) of alcohol-withdrawal mice. Alcohol consumption led to a reduction in dendritic spine density in the mPFC and HP, which was restored to normal levels by liraglutide (p < 0.001). Furthermore, liraglutide was found to augment the levels of synaptic transport-related proteins in mice subjected to alcohol withdrawal (p < 0.01). The study findings corroborate that liraglutide has the potential to mitigate alcohol consumption and ameliorate the memory impairments and anxiety induced by alcohol withdrawal. The therapeutic efficacy of liraglutide might be attributed to its role in counteracting synapse loss in the mPFC and HP regions and thus prevented relapse-like drinking in alcohol-withdrawal mice. [ABSTRACT FROM AUTHOR]

Diabetic Parkinson's disease (DP) is a progressive neurodegenerative disease with metabolic syndrome that is increasing worldwide. Emerging research suggests that cannabidiol (CBD) is a neuropharmacological compound that acts against this disease, especially CBD in nano-formulation. The safety of cannabidiol lipid nanoparticles (CBD-LNP) was evaluated by assessing in vitro cytotoxicity in neurons and therapeutic outcomes in a DP animal model, including metabolic parameters and histopathology. CBD-LNPs were fabricated by using a microfluidization technique and showed significantly lower cytotoxicity than the natural form of CBD. The DP rats were induced by streptozotocin followed by a 4-week injection of MPTP with a high-fat diet. Rats were treated orally with a vehicle, CBD, CBD-LNP, or levodopa for 4 weeks daily. As a result, vehicle-treated rats exhibited metabolic abnormalities, decreased striatal dopamine levels, and motor and memory deficits. CBD-LNP demonstrated reduced lipid profiles, enhanced insulin secretion, and restored dopamine levels compared to CBD in the natural form. CBD-LNP also had comparable efficacy to levodopa in ameliorating motor deficits and memory impairment in behavior tests. Interestingly, CBD-LNP presented migration of damaged neuronal cells in the hippocampus more than levodopa. These findings suggest that CBD-LNP holds promise as an intervention addressing both metabolic and neurodegenerative aspects of DP, offering a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

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]

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

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-cholinesterasebutyrylcholinesterase activities. Experimental approach: In this study, aqueous and hydroalcoholic extracts, hexane and ethyl acetate fractions of EC (25, 50, 100 mg/kg, i.p.), and the manna (25, 50, 100 mg/kg, gavage) were administered for 14 days alongside scopolamine (0.7 mg/kg, i.p.). Rivastigmine (reference drug) was administered for 2 weeks i.p. Mice were tested for their memory function using two behavioral models, object recognition test (ORT) and passive avoidance test (PAT). Findings/Results: Administration of scopolamine significantly impaired memory function in both behavioral models. In the PAT model, all extracts at 50 and 100 mg/kg significantly reversed the effect of memory destruction caused by scopolamine. At a lower dose of 25 mg/kg, however, none of the extracts were able to significantly change the step-through latency time. In the ORT model, however, administration of all extracts at 50 and 100 mg/kg, significantly increased the recognition index. Only the manna and the aqueous extract at 25 mg/kg were able to reverse scopolamine-induced memory impairment. Conclusions and implications: These results suggest that all forms of EC extracts improve memory impairment induced by scopolamine comparably to rivastigmine. Whether the effects are sustained over a longer period remains to be tested in future work. [ABSTRACT FROM AUTHOR]

Rationale: Phosphodiesterase 4D negative allosteric modulators (PDE4D NAMs) enhance memory and cognitive function in animal models without emetic-like side effects. However, the relationship between increased cyclic adenosine monophosphate (cAMP) signaling and the effects of PDE4D NAM remains elusive. Objective: To investigate the roles of hippocampal cAMP metabolism and synaptic activation in the effects of D159687, a PDE4D NAM, under baseline and learning-stimulated conditions. Results: At 3 mg/kg, D159687 enhanced memory formation and consolidation in contextual fear conditioning; however, neither lower (0.3 mg/kg) nor higher (30 mg/kg) doses induced memory-enhancing effects. A biphasic (bell-shaped) dose–response effect was also observed in a scopolamine-induced model of amnesia in the Y-maze, whereas D159687 dose-dependently caused an emetic-like effect in the xylazine/ketamine anesthesia test. At 3 mg/kg, D159687 increased cAMP levels in the hippocampal CA1 region after conditioning in the fear conditioning test, but not in the home-cage or conditioning cage (i.e., context only). By contrast, 30 mg/kg of D159687 increased hippocampal cAMP levels under all conditions. Although both 3 and 30 mg/kg of D159687 upregulated learning-induced Fos expression in the hippocampal CA1 30 min after conditioning, 3 mg/kg, but not 30 mg/kg, of D159687 induced phosphorylation of synaptic plasticity-related proteins such as cAMP-responsive element-binding protein, synaptosomal-associated protein 25 kDa, and the N-methyl-D-aspartate receptor subunit NR2A. Conclusions: Our findings suggest that learning-stimulated conditions can alter the effects of a PDE4D NAM on hippocampal cAMP levels and imply that a PDE4D NAM exerts biphasic memory-enhancing effects associated with synaptic plasticity-related signaling activation. [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]

Chemotherapy-induced cognitive impairment or "chemobrain" is a prevalent long-term complication of chemotherapy and one of the more devastating. Most of the studies performed so far to identify the cognitive dysfunctions induced by antineoplastic chemotherapies have been focused on treatment with anthracyclines, frequently administered to breast cancer patients, a population that, after treatment, shows a high possibility of long survival and, consequently, of chemobrain development. In the last few years, different possible strategies have been explored to prevent or reduce chemobrain induced by the anthracycline doxorubicin (DOX), known to promote oxidative stress and inflammation, which have been strongly implicated in the development of this brain dysfunction. Here, we have critically analyzed the results of the preclinical studies from the last few years that have evaluated the potential of phenolic compounds (PheCs), a large class of natural products able to exert powerful antioxidant and anti-inflammatory activities, in inhibiting DOX-induced chemobrain. Several PheCs belonging to different classes have been shown to be able to revert DOX-induced brain morphological damages and deficits associated with learning, memory, and exploratory behavior. We have analyzed the biological and molecular mechanisms implicated and suggested possible future perspectives in this research area. [ABSTRACT FROM AUTHOR]

Our study aimed to explore the impact and mechanism of Euonymus alatus leaf extract on age-dependent oxidative stress, neuroinflammation, and progressive memory impairments in aged mice. Twenty-four-month-old mice received EA-L3 (300 mg/kg/day) or the reference drug, donepezil (DPZ, 5 mg/kg/day), for 6 weeks, and learning and memory functions were detected using the Passive Avoidance Test (PAT). As expected, cognitive function deficits were detected in aged mice compared with young mice, and these deficits were significantly mitigated by dietary treatments with EA-L3. In parallel, it upregulated the brain-derived neurotrophic factor (BDNF) and subsequently activated the extracellular-signal-regulated kinase (ERK)/cAMP response element-binding (CREB) signaling in the mouse hippocampus and scopolamine-induced B35 and SH-SY5Y neuroblastoma cells. EA-L3 showed strong anti-inflammatory effects with decreased NF-κBp65, cyclooxygenase 2 (COX-2), and tumor necrosis factor alpha (TNF-α), increased interleukin (IL)-10, and doublecortin (DCX) protein expression in the hippocampus of aged mice. Similar results were also confirmed in LPS-induced BV-2 microglia and neuroblastoma cells upon treatment with EA-L3 extract. In addition, EA-L3 notably dose-dependently decreased ROS in BV2 cells after exposure to LPS. Taken together, EA-L3 might be used as a dietary supplement to alleviate oxidative stress, the deterioration of hippocampal-based memory tasks, and neuroinflammation in elderly people. [ABSTRACT FROM AUTHOR]

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC's metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the changes in Paraoxonase (PON), Carbonic Anhydrase (CA), and β-glucosidase levels of different aged rats and scopolamine-induced memory impairment rats. This study used young, adult, and middle-aged male Wistar Albino rats. Scopolamine was administered as a single dose/multiple doses and a Morris water maze (MWM) was used for spatial learning testing in rats. Enzyme-linked immunosorbent assays (ELISAs) were used to determine serum and liver PON and β-glucosidase levels. The CA enzyme activity was assayed following the hydration of CO2. As a result of the comparison of age-related and scopolamine-related changes in PON and β-glucosidase levels in liver and serum samples, no significant age-related and scopolamine-effective changes were observed in serum, while liver PON and liver β-glucosidase levels were found to change significantly. CA activity studies, on the other hand, showed that adults have the lowest CA activity compared to young and middle-aged groups and scopolamine inhibited CA activity in vivo. We found that adult rats modeled with memory impairment had statistically lower levels of liver PON and liver β-glucosidase. CA activity was also found to be significantly reduced. β-glucosidase and CA should be further investigated in terms of neurodegenerative disease risk factors, just like PON, whose importance has been determined by numerous studies in the literature. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes. Results: The current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test. When compared to the illness control, the memory-enhancing potential of novel N-benzyl pyridine-2-one derivatives was highly significant (P < 0.0001). Conclusions: The observed memory ameliorating effect of novel N-benzyl pyridine-2-one makes them as a a good choice for treatment of individuals with cognitive impairment. [ABSTRACT FROM AUTHOR]

Cisplatin, a chemotherapy drug containing platinum, is considered a neurotoxic agent. On the other hand, crocin, the primary component of saffron, possesses neuroprotective and antioxidant properties. In this study, 28 healthy adult male Wistar rats weighing 200–250 g were used (6–7 weeks old). Rats were divided into a control group (Ctr), a crocin group (Cro), a cisplatin group (Cis), and a crocin with cisplatin group (Cro + Cis). Rotarod, open field, and shuttle box tests were performed to assess balance, explorative behavior, and avoidance memory. After behavioral testing, the hippocampus was extracted to analyze oxidative stress parameters such as GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase), and MDA (malondialdehyde) activity. Shuttle box, rotarod, and open field results showed that crocin can substantially mitigate the deleterious effects of cisplatin on avoidance memory, explorative behavior, motor coordination, and balance. Crocin was also able to effectively avoid the negative effects of cisplatin on MDA, GPx, and CAT during the assessment of oxidative indicators, while the beneficial effect of crocin on cisplatin was not statistically significant in terms of SOD level. In conclusion, since free radicals produced by cisplatin are a contributing factor to memory loss and movement disorders, crocin, owing to its antioxidant properties, improved passive avoidance learning as well as motor activity. [ABSTRACT FROM AUTHOR]

We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and pP70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression. [ABSTRACT FROM AUTHOR]

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

This study aimed to investigate the effects of clinorotation induced by 2-D clinostat on the growth, tropane alkaloid production, gene expression, antioxidant capacity, and cellular defense responses in the callus tissue of Hyoscyamus niger. Callus induction was conducted by putting hypocotyl explants in the MS culture medium supplemented with 1 mgL−1 2,4-D and 1 mgL−1 BAP growth regulators. The sub-cultured calli were placed on a clinostat for 0, 3, 7, and 10 days (2.24 × 10–5 g on the edge of the callus ring). Clinorotation significantly increased callus fresh weight, dry weight, protein, carbohydrate, and proline contents compared to the control, and their maximum contents were obtained after 7 and 10 days. H2O2 level enhanced under clinorotation with a 76.3% rise after 10 days compared to control and positively affected the atropine (77.1%) and scopolamine (69.2%) productions. Hyoscyamine 6-beta hydroxylase and putrescine N-methyltransferase gene expression involved in the tropane alkaloid biosynthesis were upregulated markedly with 14.2 and 17.1-folds increase after 10 days of clinorotation, respectively. The expressions of jasmonic acid, mitogen-activated protein kinase, and ethylene-responsive element-binding transcription factor were upregulated, and the activity of peroxidase and catalase showed a 72.7 and 80% rise after 10 days. These findings suggest that microgravity can enhance callogenesis by stimulating the ROS level, which can impact the antioxidant enzymes, tropane alkaloid formation, and gene expression. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is frequently characterized by progressive and irreversible impairment of cognitive functions. However, its etiology remains poorly understood, limiting therapeutic interventions. Our previous study showed that the ethanol extract of Euonymus alatus leaves (EA) positively affected scopolamine-induced hypomnesia in the normal mouse model by promoting nuclear factor E2-related factor 2 (Nrf2) activation. Herein, we examined whether EA administration could ameliorate major AD phenotypes that are manifested in 5xFAD transgenic mice. Two-month-old mice were orally administered with EA at a dose of 50, 100, or 150 mg/kg body weight/day thrice a week for 14 weeks. We observed that EA administration improved behavioral deficits as assessed by the passive avoidance, Morris water maze, and Y-maze tasks; decreased the plasma levels of pro-inflammatory cytokines, including TNFα and IL-1β; decreased the protein expression levels of inflammatory mediators in the hippocampus; and attenuated histological damage and amyloid beta plaques in the hippocampal region of 5xFAD mouse brain. Interestingly, our data demonstrated that the effectiveness was partially attributed to quercetin, which was noted to be a component of EA. Hence, these findings suggest that a long-term administration of EA could alleviate AD symptoms and delay its progression. [ABSTRACT FROM AUTHOR]

This document discusses the role of oxidative damage in aging and age-related diseases. It highlights the potential of medicinal herbs in suppressing oxidative damage caused by reactive oxygen species (ROSs) and explores their therapeutic effects in treating age-related diseases. The document presents several studies that demonstrate the antioxidant and anti-inflammatory effects of specific medicinal herbs, such as Euonymus alatus leaf extract, baicalein, and Prunella vulgaris and Gentiana lutea combination. These findings provide valuable insights for researchers and clinicians in developing treatments for aging-related conditions. [Extracted from the article]

The New Journal of Chemistry, published by The Royal Society of Chemistry and the Centre National de la Recherche Scientifique, focuses on new directions in chemistry. This document is a contents list for the journal, providing information about the ISSN, cover image, and a list of communications and papers featured in the issue. The papers cover a range of topics including lanthanum capture, corrosion inhibition, supercapacitor applications, catalysis, and nanocomposites. Each paper explores a specific scientific concept or mechanism, offering valuable insights into various fields of research. The document also mentions other journals related to energy research and sustainable energy technologies. [Extracted from the article]

Epiberberine is one of the main constituents of Coptidis Rhizoma and has been found to be active against diseases such as hyperglycemia, hyperlipidemia, and Alzheimer's disease. However, like other alkaloids its use is limited by rapid absorption, rapid metabolism and low transport to the brain. Nanotechnology has become a method of choice for a better delivery of active principles to the brain. The current study involved the use of a nanotechnological approach for the synthesis of epiberberine-loaded chitosan-collagen nanocomposites using natural polymers chitosan and collagen. This study was aimed at increasing the efficacy of epiberberine for dementia by decreasing the release rate and enhancing the anti-oxidant and AChE inhibition properties of epiberberine. The synthesized nanocomposites were found to be of small size (25 ± 2 nm) with more or less spherical morphology and showed slow release rate. Oxidative stress and impaired levels of acetylcholinesterase (AChE) are associated with the pathophysiology of Alzheimer's disease. These nanocomposites showed in vitro and in vivo anti-oxidant and AChE inhibition activity. Further, behavioral, biochemical, ELISA and immunohistochemical parameters were also used to evaluate the efficacy of these nanocomposites in a scopolamine-induced amnesia rat model. The results showed that these nanocomposites can reduce cognitive decline and are more effective against scopolamine-induced amnesia than epiberberine and the standard drug donepezil. At a similar concentration of 1 mg kg−1 body weight, the p-values of nanocomposites were smaller (approximately 10−4 to 10−2) in comparison to epiberberine and donepezil, indicating a significant effect against scopolamine-induced amnesia. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease that results in memory impairment. Aegle marmelos (L.) Correa (AM) is used as a traditional medicine. AM leaves have the potential to inhibit acetylcholinesterase activity. This study used scopolamine to induce AD in rats. The aim of this study was to investigate the effects of AM leaf extract using this model. Motor and memory functions were tested by the motor activity and Morris water maze (MWM) tests, respectively. The density of the synaptophysin and dendritic spines in the CA1 were detected by immunofluorescence and Golgi impregnation, respectively. The hippocampal histology was reviewed by H&E staining. After the treatment, the latency times in the MWM tests of the AD groups reduced, while the motor activities showed no difference. The density of the synaptophysin of the AD groups increased after the treatments, and that of the dendritic spines also increased in all AD groups post-treatment. The hippocampal tissue also recovered. AM leaf extract can improve cognitive impairment in AD models by maintaining the presynaptic vesicle proteins and dendritic spines in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Strobilanthes cordifolia has emerged as a promising material in traditional medicine. In this study, we have made an attempt to synthesize zinc oxide nanoparticles derived from S. cordifolia leaf. The team employed a wide range of techniques including UV, FT‐IR, XRD, FE‐SEM with EDAX, HR‐TEM with SAED, DLS, Zeta potential, BET and PZC analysis to thoroughly examine the properties of the NPs. FTIR analysis provided evidence of various functional groups within the NPs. XRD analysis demonstrated the crystal nature and phase purity of the NPs. SEM analysis showcased the spherical shape of the particles, while TEM revealed their rod‐like shape with sizes averaging at approximately 10 nm. DLS analysis indicated the average particle size, and the high zeta potential value confirmed the stability and BET analysis deciphered the specific surface area of the biosynthesized NPs. The NPs confirmed strong antioxidant properties with DPPH, ABTS, and hydroxyl radicals. Enzyme studies confirmed good anti‐cholinergic activity and anti‐inflammatory efficacy, highlighting their potential therapeutic benefits. The NPs demonstrated promising wound healing properties. Overall, this research study sheds light on the medicinal aspects of zinc oxide nanoparticles from S. cordifolia leaf extract and it offers exciting prospects for future exploration and development in this field. [ABSTRACT FROM AUTHOR]

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

The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer's disease (AD). Positive allosteric modulators (PAMs) of metabotropic glutamate (mGlu) receptors were shown to be effective procognitive compounds, but little is known about their impact on eNOS expression and stability. Here, we investigated the influence of the acute and chronic administration of LY487379 or CDPPB (mGlu2 and mGlu5 PAMs), on eNOS expression in the mouse brain and the effect of the joint administration of the ligands with nitric oxide (NO) releasers, spermineNONOate or DETANONOate, in different combinations of doses, on MK-801- or scopolamine-induced amnesia in the novel object recognition (NOR) test. Our results indicate that both compounds provoked eNOS monomer formation, and CDPPB at a dose of 5 mg/kg exaggerated the effect of MK-801 or scopolamine. The coadministration of spermineNONOate or DETANONOate enhanced the antiamnesic effect of CDPPB or LY487379. The best activity was observed for ineffective or moderate dose combinations. The results indicate that treatment with mGluR2 and mGluR5 PAMs may be burdened with the risk of promoting eNOS uncoupling through the induction of dimer dissociation. Administration of the lowest possible doses of the compounds with NO• donors, which themselves have procognitive efficacy, may be proposed for the treatment of schizophrenia or AD. [ABSTRACT FROM AUTHOR]

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development. [ABSTRACT FROM AUTHOR]

Rationale: Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior. Objectives: In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated. Methods: Wistar male rats (200–220 g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10 mg/kg, and (5) methamphetamine + alpha-lipoic acid 40 mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20 mg/kg, 2 h interval). Alpha-lipoic acid was injected 30 min, 24 h, and 48 h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated. Results: Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property. [ABSTRACT FROM AUTHOR]

Conventional transnasal brain-targeted drug delivery strategies are limited by nasal cilia clearance and the nasal mucosal barrier. To address this challenge, we designed dissolving microneedles combined with nanocarriers for enhanced nose-to-brain drug delivery. To facilitate transnasal administration, a toothbrush-like microneedle patch was fabricated with hyaluronic acid-formed microneedles and tannic acid-crosslinked gelatin as the base, which completely dissolved in the nasal mucosa within seconds leaving only the base, thereby releasing the loaded cyclodextrin-based metal-organic frameworks (CD-MOFs) without affecting the nasal cilia and nasal microbial communities. As nanocarriers for high loading of huperzine A, these potassium-structured CD-MOFs, reinforced with stigmasterol and functionalized with lactoferrin, possessed improved physical stability and excellent biocompatibility, enabling efficient brain-targeted drug delivery. This delivery system substantially attenuated H 2 O 2 - and scopolamine-induced neurocyte damage. The efficacy of huperzine A on scopolamine- and D-galactose & AlCl 3 -induced memory deficits in rats was significantly improved, as evidenced by inhibiting acetylcholinesterase activity, alleviating oxidative stress damage in the brain, and improving learning function, meanwhile activating extracellular regulated protein kinases-cyclic AMP responsive element binding protein-brain derived neurotrophic factor pathway. Moreover, postsynaptic density protein PSD-95, which interacts with two important therapeutic targets Tau and β-amyloid in Alzheimer's disease, was upregulated. This fruitful treatment was further shown to significantly ameliorate Tau hyperphosphorylation and decrease β-amyloid by ways including modulating beta-site amyloid precursor protein cleaving enzyme 1 and a disintegrin and metalloproteinase 10. Collectively, such a newly developed strategy breaks the impasse for efficient drug delivery to the brain, and the potential therapeutic role of huperzine A for Alzheimer's disease is further illustrated. [Display omitted] • Lactoferrin-functionalized stigmasterol-reinforced CD-MOFs were developed for brain-targeting drug delivery. • Microneedles-mediated nose-to-brain drug delivery strategy were demonstrated. • Huperzine A improved memory deficits via regulating ERK-CREB-BDNF, PSD-95/Tau, and Aβ-BACE1-ADAM10 pathways. [ABSTRACT FROM AUTHOR]

Background: Camellia sasanqua Thunb. is an essential woody ornamental plant. Our continuous observation found that scale insects often infest C. sasanqua all year round in Kunming, China, resulting in poor growth. Scientifically preventing and controlling the infestation of scale insects should be paid attention to, and the mechanism of scale insects influencing C. sasanqua should be used as the research basis. Results: The scale insect was identified as Pseudaulacaspis sasakawai Takagi. We analyzed transcriptome sequencing data from leaves of C. sasanqua infested with scale insects. A total of 1320 genes were either up-regulated or down-regulated and differed significantly in response to scale insects. GO (Gene Ontology) annotation analysis showed that the pathway of catalytic activity, binding, membrane part, cell part, and cellular process were affected. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that most DEGs (differentially expressed genes) involved in plant hormone signal transduction, MAPK signaling pathway, flavonoid biosynthesis, tropane, piperidine and pyridine alkaloid biosynthesis. We also observed that the expression of galactose metabolism and carotenoid biosynthesis were significantly influenced. In addition, qRT-PCR (quantitative real-time PCR) validated the expression patterns of DEGs, which showed an excellent agreement with the transcriptome sequencing. Conclusions: Our transcriptomic analysis revealed that the C. sasanqua had an intricate resistance strategy to cope with scale insect attacks. After sensing the attack signal of scale insects, C. sasanqua activated the early signal MAPK (mitogen-activated protein kinase) to activate further transcription factors and Auxin, ET, JA, ABA, and other plant hormone signaling pathways, ultimately leading to the accumulation of lignin, scopolin, flavonoids and other secondary metabolites, produces direct and indirect resistance to scale insects. Our results suggested that it provided some potential resources of defense genes that would benefit the following resistance breeding in C. sasanqua to scale insects. [ABSTRACT FROM AUTHOR]

The sympathoadrenal medullary system and the hypothalamic-pituitaryadrenal axis are both activated upon stressful events. The release of catecholamines, such as dopamine, norepinephrine (NE), and epinephrine (EPI), from sympathetic autonomic nerves participate in the adaptive responses to acute stress. Most theories suggest that activation of peripheral b-adrenoceptors (b-ARs) mediates catecholamines-induced memory enhancement. These include direct activation of b-ARs in the vagus nerve, as well as indirect responses to catecholamine-induced glucose changes in the brain. Excessive sympathetic activity is deeply associated with memories experienced during strong emotional stressful conditions, with catecholamines playing relevant roles in fear and traumatic memories consolidation. Recent findings suggest that EPI is implicated in fear and traumatic contextual memories associated with post-traumatic stress disorder (PTSD) by increasing hippocampal gene transcription (e.g., Nr4a) downstream to cAMP response-element protein activation (CREB). Herein, we reviewed the literature focusing on the molecular mechanisms underlying the pathophysiology of memories associated with fear and traumatic experiences to pave new avenues for the treatment of stress and anxiety conditions, such as PTSD. [ABSTRACT FROM AUTHOR]

We have synthesized 22 C-1 functionalized-N-aryl-1,2,3,4-tetrahydroisoquinoline derivatives showing biological activities towards cholinergic enzymes. Synthesis was performed using visible-light-promoted photo-redox chemistry, starting from a common intermediate, and the application of this synthetic methodology drastically simplified synthetic routes and purification of desired compounds. All synthesized derivates were divided into four groups based on the substituents in the C-1 position, and their inhibition potencies towards two cholinergic enzymes, acetyl- and butyrylcholinesterase were evaluated. Most potent derivatives were selected, and kinetic analysis was further carried out to obtain insights into the mechanisms of inhibition of these two enzymes. Further validation of the mode of inhibition of cholinergic enzymes by the two most potent THIQ compounds, 3c and 3i, was performed using fluorescence-quenching titration studies. Molecular docking studies further confirmed the proposed mechanism of enzymes' inhibition. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the selected most potent derivatives were performed using Swiss ADME tool. This was followed by UPLC-assisted log P determination and in vitro BBB permeability studies performed in order to assess the potential of the synthesized compounds to pass the BBB. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disorder characterized by cognitive decline, memory loss, behavioral changes, and other neurological symptoms. Considering the urgent need for new AD therapeutics, in the present study we designed, synthesized, and evaluated multitarget compounds structurally inspired by sulfonylureas and pitolisant with the aim of obtaining multitarget ligands for AD treatment. Due to the diversity of chemical scaffolds, a novel strategy has been adopted by merging into one structure moieties displaying H3R antagonism and acetylcholinesterase inhibition. Eight compounds, selected by their binding activity on H3R, showed a moderate ability to inhibit acetylcholinesterase activity in vitro, and two of the compounds (derivatives 2 and 7) were also capable of increasing acetylcholine release in vitro. Among the tested compounds, derivative 2 was identified and selected for further in vivo studies. Compound 2 was able to reverse scopolamine-induced cognitive deficits with results comparable to those of galantamine, a drug used in clinics for treating AD. In addition to its efficacy, this compound showed moderate BBB permeation in vitro. Altogether, these results point out that the fragment-like character of compound 2 leads to an optimal starting point for a plausible medicinal chemistry approach for this novel strategy. [ABSTRACT FROM AUTHOR]

The present research work was intended to carry out the neuroprotective efficacy of banana peel powder (BPP) in scopolamine induced amnesia in zebrafish. The effect of BPP was assessed by Novel tank test, Y-Maze test and Color-biased appetite conditioning T-Maze test. In novel tank test, the different concentrations of BPP (12.5, 25 and 50 mg/L) showed dose dependent increase in the number of entries to top, time spent in top, latency to enter top and total distance travelled in tank whereas decrease in number of entries to bottom and time spent in bottom as compared to scopolamine control group. In Y-Maze test, BPP at various strengths exhibited dose dependent significant increase in number entries to novel arm, time spent in novel arm and total distance travelled in the maze as compared to scopolamine control group. The different concentrations of BPP showed significant decrease in acetylcholinesterase (AChE) and MDA content in brain homogenate of zebrafish as compared to scopolamine control group. In T-Maze test BPP at 12.5, 25 and 50 mg/L exhibited dose dependent significant increase in number of entries to green arm and time spent in green arm whereas significant decrease in number of entries to red arm and time spent in red arm as compared to scopolamine control group in dose dependent manner. The results obtained in this study conclude that, BPP could effectively improve memory impairments in a scopolamine induced zebrafish model of amnesia by enhancing the function of the behavioral response and antioxidant enzymes in the amnesic zebrafish model. [ABSTRACT FROM AUTHOR]

The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria named 6-hydroxy-L-nicotine (6HLN) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those published between 1992 and 2023, was conducted. The search focused specifically on articles about nicotine metabolites, memory, oxidative stress, and cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 212 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6HLN. [ABSTRACT FROM AUTHOR]

We aim to investigate the myopic control effect of high-concentration atropine (ATR) and dual-focus contact lenses (DFCLs). A retrospective cohort study was conducted. A total of 182 eyes in 91 individuals who used high-concentration ATR (0.125%) and another 70 eyes in 35 individuals who used DFCLs were enrolled in the ATR and DFCL groups, respectively. The primary outcomes were spherical equivalent refraction (SER) progression and axial length (AXL) elongation. The generalized estimate equation was utilized to yield the adjusted odds ratio (aOR) and 95% confidence interval (CI) of cycloplegic SER progression and AXL elongation between groups. According to the multivariable analysis, the change in cycloplegic SER progression was similar between the DFCL and ATR groups (aOR: 1.305, 95% CI: 0.247–2.515, p = 0.803). The DFCL group demonstrated a numerically higher rate of AXL elongation compared to the ATR group (aOR: 1.530, 95% CI: 0.980–1.894, p = 0.051). In the subgroup analysis, cycloplegic SER progression was insignificant between ATR and DFCL users in different subgroups (all p > 0.05). The DFCL patients with moderate astigmatism and high AXL (both p < 0.001) presented a high risk of AXL elongation. In conclusion, DFCL usage demonstrated similar myopic control of cycloplegic SER and AXL compared to high-concentration ATR, while DFCLs showed lower AXL control, mainly in patients with moderate astigmatism and high AXL. [ABSTRACT FROM AUTHOR]

This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, cholineacetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-a, interleukin-1β (IL-1β), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complicated disease for which there are still no ideal one-target drugs, while multi-target drugs are closer to ideal drugs and will provide new solutions for the clinical treatment of AD. DL0410 is a promising multi-target drug candidate for AD treatment that is not only a significant inhibitor against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) but also an antagonist of histamine H3 receptor (H3R), and its therapeutic efficacy in treating cognitive dysfunction has been validated in a series of AD-related animal models, including scopolamine-induced mice, D-galactose-induced and Aβ-induced mice, and APP/PS1 and SAMP8 mice. Although the structure of DL0410 has been analyzed using various detection techniques, such as MS and NMR, its three-dimensional crystal structure still requires further confirmation. In this study, the crystal of DL0410 was grown in aqueous solution, and its structure was detected using the X-ray diffraction method. The crystal data, atomic coordinates, bond lengths, angles, and hydrogen bonds of DL0410 were obtained. Its stability was proven by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Based on this study, the molecular docking of DL0410 with AChE, BuChE, and H3R was performed to uncover their interaction mechanisms and explain their bioactivities. This study provides important information for new multi-target drug design and the research and development of new drugs for AD treatment. [ABSTRACT FROM AUTHOR]

Tomatillo (Physalis philadelphica Lam.) has been interested for its medicinal bioactive compounds, which can be promoted using biostimulants. This study was conducted to evaluate the foliar application of arginine (0, 300, 600, and 900 μM) and folic acid (0, 100, and 200 μM) on the metabolites content and antioxidant activity of tomatillo fruits. Results showed that the combined application of higher concentrations of arginine and folic acid significantly improved the content of acid ascorbic, phenolic compounds, flavonoids, tropane alkaloids (scopolamine and atropine), total alkaloid, physalins, and antioxidant activity of tomatillo fruits. The ascorbic acid content increased by 49.0 and 54.7% under Arg (900 μM) + FA (100 or 200 μM) treatments, respectively, compared to untreated plants. The highest total phenolic and flavonoid contents as well as tropane and total alkaloids were recorded in plants treated with 900 μM Arg + 200 μM FA. The atropine content was higher than the scopolamine content. The physalins content and DPPH radical scavenging capacity of fruits under Arg (900 μM) + FA (100 or 200 μM) treatments increased by 2.1 and 1.7 times, respectively, in comparison to the control. Significant positive correlation coefficients (r = 0.92–0.99) were found between all phytochemical parameters, which indicates that acid ascorbic, phenolic compounds, flavonoids, physalins, and alkaloids are related to the antioxidant activity of tomatillo fruits. Therefore, exogenous application of arginine and folic acid could be considered as a valuable and safe tool to improve the pharmaceutical potential of tomatillo fruits. [ABSTRACT FROM AUTHOR]

Dry eye disease is a common condition in patients of all ages, causing discomfort and potential visual problems. Current treatments, including artificial tears and anti-inflammatory drugs, have certain limitations, encouraging research into alternative therapies. We investigated the therapeutic potential of multi-wavelength light-emitting diode (LED) irradiation of mice with dry eye. First, we showed that multi-wavelength LED irradiation was non-toxic to human corneal epithelial cells and improved cell viability. We then used a scopolamine-induced mouse model of dry eye to assess the effects of multi-wavelength LED irradiation on various clinical parameters. This treatment increased the tear volume and reduced corneal irregularity, thus improving dry eye. Histological analysis revealed that multi-wavelength LED irradiation protected against corneal epithelial damage and the associated reduction in epithelial thickness and would thus improve the corneal health of dry eye patients. Multi-wavelength LED irradiation significantly reduced the corneal levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; the treatment was thus anti-inflammatory. Our results suggest that multi-wavelength LED irradiation may serve as a safe and effective treatment for dry eye, alleviating symptoms, reducing inflammation, and promoting corneal health. [ABSTRACT FROM AUTHOR]

Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the current study is to assess the potential antiemetic properties of QUA using an in vivo and in silico approach. In this experiment, 4-day-old chicks were purchased to induce emesis by orally administering copper sulfate pentahydrate (CuSO4·5H2O) at a dose of 50 mg/kg (orally). Domperidone (DOM) (6 mg/kg), Hyoscine (HYS) (21 mg/kg), and Ondansetron (OND) (5 mg/kg) were treated as positive controls (PCs), and distilled water and a trace amount of Tween 80 mixture was employed as a negative control (NC). QUA was given orally at two distinct doses (25 and 50 mg/kg). Additionally, QUA (50 mg/kg) and PCs were administered separately or in combination to assess their antagonistic or synergistic effects on the chicks. The binding affinity of QUA and referral ligands towards the serotonin receptor (5HT3), dopamine receptors (D2 and D3), and muscarinic acetylcholine receptors (M1–M5) were estimated, and ligand–receptor interactions were visualized through various computational tools. In vivo findings indicate that QUA (25 and 50 mg/kg) has a significant effect on reducing the number of retches (16.50 ± 4.65 and 10.00 ± 4.19 times) and increasing the chick latency period (59.25 ± 4.75 and 94.25 ± 4.01 s), respectively. Additionally, QUA (50 mg/kg) in combination with Domperidone and Ondansetron exhibited superior antiemetic effects, reducing the number of retches and increasing the onset of emesis-inducing time. Furthermore, it is worth noting that QUA exhibited the strongest binding affinity against the D2 receptor with a value of −9.7 kcal/mol through the formation of hydrogen and hydrophobic bonds. In summary, the study found that QUA exhibited antiemetic activity in chicks, potentially by interacting with the D2 receptor pathway. [ABSTRACT FROM AUTHOR]

Anisodus tanguticus is a valuable plant for extracting tropane alkaloids. However, the mechanisms by which plant microbiome mediate the accumulation of tropane alkaloids in Anisodus tanguticus are still not well understood. In this study, we collected 55 wild Anisodus tanguticus populations on the Tibetan Plateau and the tropane alkaloids content, and root-related bacteria and fungi diversitywere analyzed using HPLC and 16 s rDNA and ITS sequencing. The results showed that tropane alkaloids content has obvious geographical distribution characteristics. Anisodine content had a significant positive correlation with latitude, while anisodamine and atropine content had a significant negative correlationwith latitude. Variation partition analysis (VPA) showed that root endophytes play a significant role in promoting tropane alkaloid production in Anisodus tanguticus roots. The root endophytes alone explained 14% of the variation, which was the largest contributor. Soil properties variables could independently explain 5% of the variation, and climate variables could explain 1% of the variation.Of these, endophytic fungi alone accounted for 11%, while bacteria explained only 5%. Random forests and Mantel test showed that different regionally enriched endophytic fungi have a greater impact on the accumulation of tropane alkaloids than the whole endophytic fungi. Richness and relative abundance of enriched endophytic fungi in Hengduan-Qilian Mountains (HQ) group has a significant positive correlation with anisodine content, while richness and relative abundance of enriched endophytic fungi in Himalayas-Hengduan Mountains (HH) group has a significant positive correlation with anisodamine and atropine content. And, these enriched endophytic fungi have high network connectivity and distributed in separate network modules. This study further confirmed that endophytes were closely related to tropane alkaloids accumulation in Anisodus tanguticus and contribute to promote sustainable development, cultivation, and precision medicine of Anisodus tanguticus. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multifactorial, rapidly progressing neurodegenerative disorder. As the exact cause of the disease is still unclear, the drug development is very challenging. This review encompasses the commonly used AD models involving various chemicals, heavy metals and endogenous substances induced models and the transgenic models. It also provides insight into the reliable emerging models of AD that may overcome the shortcomings associated with available models. Chemicals like streptozotocin, scopolamine, colchicine and okadaic acid render the animal susceptible to neuroinflammation and oxidative stress induced neurodegeneration along with amyloid-β deposition and tau hyperphosphorylation. Similarly, endogenous substances like acrolein and amyloid-β 1–42 are efficient in inducing the major pathologies of AD. Heavy metals like aluminum and fluoride and mixture of these have been reported to induce neurotoxicity therefore are used as animal models for AD. Transgenic models developed as a result of knock-in or knock-out of certain genes associated with AD including PDAPP, APP23, Tg2576, APP/PS1, 3 × Tg and 5 × FAD have also been incorporated in this study. Further, emerging and advanced pathomimetic models of AD are provided particular interest here which will add on to the current knowledge of animal models and may aid in the drug development process and deepen our understanding related to AD pathogenesis. These newly discovered models include oAβ25-35 model, transgenic model expressing 82-kDa ChAT, oDGal mouse and APP knock-in rat. This study may aid in the selection of suitable model for development of novel potent therapeutics and for exploring detailed pathogenic mechanism of AD. [ABSTRACT FROM AUTHOR]