Acetylcholinesterase Research Articles

Design, synthesis, in silico, and in vitro evaluation of pyrrol-2-yl-phenyl allylidene hydrazine carboximidamide derivatives as AChE/BACE 1 dual inhibitors.

Alzheimer's disease (AD) manifests as a progressive decline in cognitive function and mental behavior. Targeting two crucial enzymes associated with AD, acetylcholinesterase (AChE) and BACE 1 (Beta-site APP Cleaving Enzyme), in combination, holds promise for therapeutic breakthroughs. In this study, 40 derivatives of pyrrol-2-yl-phenyl allylidene hydrazine carboximidamide were designed based on prior research. These derivatives underwent synthesis and assessment for their inhibitory potential against AChE and BACE 1. ADME predictions indicated favorable physicochemical properties for these compounds. The findings offer novel avenues for exploring the dual inhibition of AChE and BACE 1 as a promising therapeutic strategy for AD.

In vitro molluscicidal activity and biochemical impacts of some thiophene derivatives against the glassy clover snail, Monacha obstructa (Pfeiffer)

BackgroundThe glassy clover snail, Monacha obstructa (Pfeiffer), is considered one of the major agricultural pests that ruin many field crops, vegetables, orchards of fruits, plants of ornament as well as many other plantations. Synthesis of the Schiff base ligand, namely bis-[4-benzylidene-thiophene-2′-yl] methane (L), produced from the reaction between thiophene-2-carboxaldehyde and diaminodiphenylmethane (MDA), alongside its copper complex were conducted. The output chemical compounds were evaluated in vitro for their molluscicidal activity against the glassy clover snail, M. obstructa by performing the contact technique. Stock solutions were prepared via using (distilled water + DMF) mixture. Furthermore, the impact of these compounds on some critical biochemical indicators: cholesterol, total protein, and acetylcholinesterase (AChE), was evaluated.ResultsThe outcome results demonstrated the significantly higher molluscicidal activity of the Cu(II) chelate compared to its free ligand (L), which in turn reveals the importance of metal chelation in enhancing toxicity against the target species. Particularly, the LC25 and LC50 values are (27.25, 34.65) and (17.88, 25.31) ppm for the ligand (L) and its copper construction, respectively. Additionally, the data confirmed the significant effectiveness of the tested compounds on the assessed biochemical indicators of treated snails. Total protein and cholesterol levels were elevated after treatment with both the ligand (L) and its copper complex while AChE activity increased after treatment with the ligand (L) and reduced upon the exposure to the Cu(II) chelate.ConclusionsThe findings established that the copper complex exhibited a markedly higher molluscicidal activity compared to the free ligand (L). Also, the results confirmed the significant effects of the investigated compounds on the assessed biochemical indicators of treated M. obstructa snails.

Repurposing Duloxetine as a Potent Butyrylcholinesterase Inhibitor: Potential Cholinergic Enhancing Benefits for Elderly Individuals with Depression and Cognitive Impairment.

Despite the advent of new treatment strategies, cholinesterase inhibitors (ChEIs) are still the go-to treatment for dementia disorders. ChEIs act by inhibiting the main acetylcholine-degrading enzyme, acetylcholinesterase (AChE). Nonetheless, accumulating evidence indicates that the impact of inhibition of the sister enzyme, butyrylcholinesterase (BChE), could be even broader in older adults due to the multifaceted role of BChE in several biological functional pathways. Therefore, we employed an in silico modeling-based drug repurposing strategy to identify novel potent BChE inhibitors from the FDA drug database. This was followed by in vitro screening and ex vivo enzyme kinetic validation using human plasma samples as the source of BChE. The analysis revealed that the antidepressant drug, duloxetine, inhibited BChE with high selectivity in comparison to AChE. In contrast, two other antidepressants, namely, citalopram and escitalopram exhibited a weak to moderate activity. Ex vivo enzyme inhibition kinetic analyses indicated that duloxetine acted as a competitive inhibitor of BChE with an inhibition constant (K i) of 210 nM. This K i value is comparable with 100-400 nM concentration of duloxetine following normal dosages in humans, thereby indicating that duloxetine should be able to induce a pharmacologically and biologically relevant in vivo inhibition of BChE. Additionally, we performed the enzyme inhibition kinetic assessment in parallel for ethopropazine, a known potent selective BChE inhibitor, and physostigmine, a dual inhibitor of AChE and BChE. These analyses indicated that duloxetine should be considered a potent BChE inhibitor since its K i was comparable with ethopropazine (K i = 150 nM) but was 4 times smaller than that of physostigmine (K i = 840 nM). In conclusion, this study reports the discovery of duloxetine being a highly potent selective competitive BChE inhibitor. This, in turn, indicates that duloxetine could be the choice of antidepressive treatment in older adults with both depressive and dementia symptoms since it may offer additional clinically beneficial effects via this secondary mode of cholinergic enhancing action.

UPLC-MS/MS-based metabolomics and chemometrics unveil metabolic patterns and their regulatory pathways over the course of pumpkin seeds (Cucurbita maxima) germination

While pumpkin seeds (Cucurbita maxima) are regarded as agro-industrial waste, they serve as powerhouses packed with a plethora of valuable compounds with potential nutraceutical significance. The present work offers an integrated view of metabolites dynamics and their regulatory pathways over the course of pumpkin seeds germination and their potential entanglements on Alzheimerʼs disease (AD) mitigation through Ultra Performance Liquid Chromatography-mass spectrometry (UPLC-MS/MS) analysis and chemometrics. A total of 76 compounds spanning amino acids, phenolic acid, flavonoids, lignans, vitamins, fatty acids, phospholipids and phytosterols were annotated revealing changing trends during germination process. Coincidentally, orthogonal projection to latent structures-discriminant analysis (OPLS-DA) demonstrated a clear separation trend among the five pumpkin samples assuring their chemical heterogeneity. Complementarily, OPLS-DA models were constructed in different timepoint comparisons to pick out the significant metabolic features which were subsequently imported into MetaboAnalyst 5.0 (https://www.metaboanalyst.ca/) software for metabolic pathway enrichment analysis. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed biosynthesis of unsaturated fatty acids, phenylpropanoid biosynthesis, glycerophospholipid metabolism and phenylalanine, tyrosine and tryptophan biosynthesis as the top predictive metabolic pathways associated with significant phytochemical shifts during germination process. Importantly, our efficacy experimental results dissected that 5 d and 7 d sprouted samples exerted noteworthy inhibitory potentials against acetylcholine esterase (AChE) and monoamine oxidase (MAO-B) enzymes. OPLS-derived coefficients plots portrayed that docosahexaenoic acid, oleic acid, lirioresinol A and tocotrienols dramatically augmented during germination were probably ascribed to promising AChE and MAO-B inhibitory activities. These findings offer a turning point for using pumpkin sprouts with an appreciable biochemical content to pursue the concept of nutritional therapy and accelerate perpetual influx of novel bioproducts to rectify AD.

Larvicidal potency of four Egyptian herbs on Culex pipiens larvae: Phytochemical composition and molecular networking for most potent extracts

Utilizing synthetic insecticides to control mosquito populations has many adverse side effects as they can cause environmental pollution and insecticide resistance. Therefore, the search for eco-friendly and effective mosquito control agents has led to the exploration of plant extracts with larvicidal efficacy. In this study, we aimed to explore the larvicidal activity of four Egyptian plant extracts: Rosmarinus officinalis, Melissa officinalis, Cichorium intybus, and Beta vulgaris var. cicla against Culex pipiens and to identify the chemical constituents present in the active extracts. The methanolic extracts of the four plants were prepared and tested against the third instar larvae of C. pipiens using a standard method. The lethal concentrations (LC50 and LC90) were calculated using probit analysis. The active extracts were subjected to ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS/MS) analysis and the data were processed using the global natural products social molecular networking (GNPS) platform to generate molecular networks and identify the compounds based on spectral similarity and database matching. The methanolic extracts of R. officinalis L. and M. officinalis L. had the highest larvicidal activity, where LC50 values were 9.795 and 26.505 μg/mL, respectively. Their exposure caused a high mortality rate and disrupted the biochemical and physiological parameters (total carbohydrates, total lipids, total protein, acetylcholinesterase (AChE), and glutathione S-transferase (GST) in the body of C. pipiens when compared with Cichorium intybus (Chicory) and Beta vulgaris var. cicla (Chard). The UPLC-MS/MS analysis with the aid of the GNPS platform, revealed the presence of 23 and 41 metabolites from R. officinalis L. and M. officinalis L., respectively. The identified metabolites may act as larvicidal agents by interfering with the physiological or biochemical processes of the mosquito larvae. Overall, the findings suggest that the methanolic extracts of R. officinalis and M. officinalis are potential sources of natural larvicides for mosquito control.

Pressurized liquid extraction with ethanol in an intermittent process for rice bran oil: Evaluation of process variables on the content of β-sitosterol and phenolic compounds, antioxidant capacity, acetylcholinesterase inhibitory activity, and oil quality

Rice bran is rich in lipids and normally contains the enzyme lipase, which degrades these lipids, making the oil unsuitable for consumption. This study analyzed a sustainable technique for extracting rice bran oil using ethanol as a solvent and compared this with traditional methods that use petroleum-derived solvents that are considered unsustainable and harmful to health. The pressurized liquid extraction (PLE) of this oil in an intermittent process showed yields between 24.83% and 27.22%, which is higher than those reported in the literature due to polar compounds in the extracted oils. The oil's acidity ranged from 2.79% to 3.22%, and the oxidative stability ranged from 0.04 h to 0.16 h. The levels of β-Sitosterol, phenolic compounds, acetylcholinesterase (AChE) inhibitory activity, and antioxidant capacity were also evaluated. The results suggest that the PLE in an intermittent process can be a sustainable and effective alternative for the extraction of rice bran oil using ethanol as a solvent, providing satisfactory yields and preserving the quality of the oil.

Speech-related parameters are sensitive measures of acetylcholinesterase inhibitor therapy in mild Alzheimer's disease.

Our aim was to find out whether speech-related temporal parameters (SRTPs) are sensitive indicators of the clinical outcome in acetylcholinesterase (AChE) inhibitor therapy with donepezil, compared to the standard cognitive Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) used in clinical trials. In this 24-week-long, naturalistic, self-control, open-labeled, prospective pilot study with 10 mg donepezil on 20 mild AD patients, cognitive functions were evaluated using 15 different SRTPs analyzed by automatic speech recognition in the Speech-Gap Test® compared to ADAS-Cog test results. Among the SRTPs, the filled pause duration ratio significantly improved after 12 weeks of donepezil treatment. During the 24-week follow-up, additional SRTPs such as the filled pause count ratio and the filled pause frequency showed significant benefits. ADAS-Cog total scores showed a slight but not significant improvement compared to baseline after 12 and 24 weeks of donepezil treatment. Among the ADAS-Cog subtests, only orientation improved significantly after 24 weeks of donepezil treatment. Our results indicate that subtle changes in SRTPs measured by the Speech-Gap Test® could be considered as sensitive indicators of the efficacy of the pharmacotherapy in mild AD. According to our data, other cognitive domains did not show improvement in response to donepezil therapy rating by ADAS-Cog. Based on all of this, it is likely that examining and evaluating speech parameters may play an important role in determining the effects of pharmacological treatment of mild AD. The novelty of our study is that it applies the measurement of linguistic parameters as primary outcomes during a drug trial of mild AD in scientific research for the first time.

Cannabidiol enhances socially transmitted food preference: a role of acetylcholine in the mouse basal forebrain.

Rodents acquire food information from their conspecifics and display a preference for the conspecifics' consumed food. This social learning of food information from others promotes the survival of a species, and it is introduced as the socially transmitted food preference (STFP) task. The cholinergic system in the basal forebrain plays a role in the acquisition of STFP. Cannabidiol (CBD), one of the most abundant phytocannabinoids, exerts its therapeutic potential for cognitive deficits through versatile mechanisms of action, including its interaction with the cholinergic system. We hypothesize a positive relationship between CBD and STFP because acetylcholine (ACh) is involved in STFP, and CBD increases the ACh levels in the basal forebrain. Male C57BL/6J mice were trained to acquire the STFP task. We examined whether CBD affects STFP memory by administering CBD (20mg/kg, i.p.) before the STFP social training. The involvement of cholinergic system in CBD's effect on STFP was examined by knockdown of brain acetylcholinesterase (AChE), applying a nonselective muscarinic antagonist SCO (3mg/kg, i.p.) before CBD treatment, and measuring the basal forebrain ACh levels in the CBD-treated mice. We first showed that CBD enhanced STFP memory. Knockdown of brain AChE also enhanced STFP memory, which mimicked CBD's effect on STFP. SCO blocked CBD's memory-enhancing effect on STFP. Our most significant finding is that the basal forebrain ACh levels in the CBD-treated mice, but not their control counterparts, were positively correlated with mice's STFP memory performance. This study indicates that CBD enhances STFP memory in mice. Specifically, those which respond to CBD by increasing the muscarinic-mediated ACh signaling perform better in their STFP memory.

Bioaccumulation and behavioral response patterns of crucian carp (Carassius carassius) after carbamazepine exposure and elimination

The antiepileptic drug carbamazepine (CBZ) has been widely detected in freshwater, yet its toxic actions in fish at multiple endpoints and the subsequent recovery patterns of the impacted are less discussed. This study investigated the bioaccumulation, physiological and behavioral changes of crucian carp (Carassius carassius) following CBZ exposure (G1 = 6.15 μg/L, G2 = 61.5 μg/L, G3 = 615 μg/L, G4 = 6150 μg/L) and subsequent recovery. Our results showed that CBZ was more likely to accumulate in the liver and brain than in the gills. A concentration-dependent phenomenon was observed; however, the residual CBZ decreased to similar levels after recovery. The behavioral indicators (i.e. feeding, social and spontaneous swimming) were significantly inhibited after 7-days of CBZ exposure, and only recovered at low concentration treatment (G1) after 7-days recovery in CBZ-free water. The acetylcholinesterase (AChE) activity in the brain and superoxide dismutase (SOD) activity in the liver and gills were induced after CBZ exposure and returned to normal levels after 7-days of recovery. In contrast, the inhibition of catalase (CAT) activity caused by CBZ exposure persisted in the high concentration treatment (G4) after recovery. Furthermore, correlation analysis indicated that changes in feeding behavior were closely related to the variation of CBZ concentrations in tissues, and the persistence of abnormal swimming and social behavior was closely related to gill CAT activity. These findings contribute to explore the toxic mechanisms of CBZ and highlight the recovery process and connections between various endpoints.

New insights about the toxicity of 2,4-D: Gene expression analysis reveals modulation on several subcellular responses in Chironomus riparius

Herbicides are the main class of pesticides applied in crops and are capable of polluting the surrounding freshwater system; thus, understanding their impact on non-target species, whose mechanism of action is not described, helps to elucidate the real risks of these pollutants to the environment. 2,4-dichlorophenoxyacetic acid (2,4-D) is frequently detected in water and, due to its persistence, poses a risk to wildlife. In this way, the present work aimed to describe the implication of exposure to concentrations of 2,4-D already reported in aquatic environments in several physiological mechanisms of C. riparius at molecular and biochemical levels. To achieve this, bioassays were conducted with fourth instar larvae exposed to three concentrations of 2,4-D (0.1, 1.0, and 7.5 μg L−1). Larvae were collected after 24 and 96 h of exposure, and the expression of 42 genes, related to six subcellular mechanisms, was assessed by Real-Time PCR (RT-PCR). Besides, the activity of the enzymes catalase (CAT), glutathione S-transferase (GST), and acetylcholinesterase (AChE) was determined. The main metabolic route altered after exposure to 2,4-D was the endocrine system (mainly related to 20-hydroxyecdysone and juvenile hormone), confirming its endocrine disruptor potential. Four of the eleven stress response genes studied were down-regulated, and later exposure modulated DNA-repair genes suggesting genotoxic capacity. Moreover, only one gene from each detoxification phase was modulated at short exposure to 1.0 μg L−1. The molecular responses were not dose-dependent, and some early responses were not preserved after 96 h, indicating a transient response to the herbicide. Exposure to 2,4-D did not alter the activity of CAT, GST, and AChE enzymes. The responses described in this study reveal new mechanistic pathways of toxicity for 2,4-D in non-target organisms and highlight potential ecological consequences for chironomids in aquatic systems at the edges of agricultural fields.

Eco-toxicity assessment of polypropylene microplastics in juvenile zebrafish (Danio rerio)

In recent years, everyone has recognized microplastics as an emerging contaminant in aquatic ecosystems. Polypropylene is one of the dominant pollutants. The purpose of this study was to examine the effects of exposing zebrafish (Danio rerio) to water with various concentrations of polypropylene microplastics (11.86 ± 44.62 μm), including control (0 mg/L), group 1 (1 mg/L), group 2 (10 mg/L), and group 3 (100 mg/L) for up to 28 days (chronic exposure). The bioaccumulation of microplastics in the tract was noted after 28 days. From the experimental groups, blood and detoxifying organs of the liver and brain were collected. Using liver tissues evaluated the toxic effects by crucial biomarkers such as reactive oxygen species, anti-oxidant parameters, oxidative effects in protein & lipids, total protein content and free amino acid level. The study revealed that the bioaccumulation of microplastics in the organisms is a reflection of the oxidative stress and liver tissue damage experienced by the group exposed to microplastics. Also, apoptosis of blood cells was observed in the treated group as well as increased the neurotransmitter enzyme acetylcholine esterase activity based on exposure concentration-dependent manner. The overall results indicated bioaccumulation of microplastics in the gut, which led to increased ROS levels. This consequently affected antioxidant biomarkers, ultimately causing oxidation of biomolecules and liver tissue injury, as evidenced by histological analysis. This study concludes that chronic ingestion of microplastics causes considerable effects on population fitness in the aquatic environment, as well as other ecological complications, and is also critical to understand the magnitude of these contaminants' influence on ichthyofauna.

Assessment of organochlorine pesticide pollution in Donax trunculus from Agadir Bay (Center of Morocco): Utilization of integrated biomarkers

This study investigated the impact of seasonal organochlorine pesticide pollution on the physiological responses of Donax trunculus at Aghroud Beach during 2009 and 2010. Significant findings include the detection of six pesticides, with Endosulfan S being the most prevalent, reaching concentrations up to 62.63 ng/g dry weight. Biomarker analysis revealed notable seasonal variations, with the highest Acetylcholinesterase (AChE) activity in winter 2009 and the lowest in spring 2010. Glutathione S-transferase (GST) activity peaked in autumn 2009, while Catalase (Cat) showed maximum activity in autumns of 2009 and 2010. Malondialdehyde (MDA) levels were highest in summer 2010, indicating increased oxidative stress and lipid peroxidation during this period. Integrated Biomarker Response (IBR) values were highest in autumns, suggesting significant pollution stress. Principal Component Analysis (PCA) revealed strong correlations: a synergy between GST and Cat, and positive links between MDA and lipids, as well as AChE and Endosulfan B. This study highlights the efficacy of using integrated biomarker responses to assess environmental health and stresses the importance of autumn and summer monitoring due to higher pollution impacts.

Characterization of Phenolic Profile and Biological Properties of Astragalus membranaceus Fisch. ex Bunge Commercial Samples.

Astragalus membranaceus Fisch. ex Bunge (syn. Astragalus mongholicus Bunge) is one of the notable medicinal and food plants. Therefore, the aim of this study was to calculate the phenolic composition and antioxidant, antimicrobial, as well as enzyme inhibitory [acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase (TYR)] activities with chemometric approaches of the hydromethanolic and water extracts of commercial A. membranaceus samples. Ten individual phenolic compounds were determined using high-performance liquid chromatography (HPLC), and only quercetin was found at a level of above 80 µg/g DW in both extracts. Moreover, the highest antioxidant activity in DPPH, FRAP, ABTS, and CUPRAC assays was found in the sample containing the roots in loose form from USA. A. membranaceus extracts displayed the inhibition zone diameters within the range from 10 to 22 mm antimicrobial activity against S. aureus, while there were no inhibition zones in any extracts in case of E. coli. The extracts of A. membranaceous showed an inhibition rate below 40% against TYR, and among tested extracts, only two samples were able to inhibit BChE with IC50 values of above 30 µg/mL. Correlation analysis showed a highly positive relationship between their phenolic composition and antioxidant activity. Concluding, the obtained results confirmed that A. membranaceus commercial samples could be an important dietary source of natural antioxidants.

The enzyme kinetic studies, DNA protection and antioxidant activities of furan/ thiophene-2-carboxamide derivatives

Three furan and/or thiophene-2-carboxamide compounds, namely N-(furan-2-ylmethyl)thiophene-2-carboxamide (1), N-(furan-2-carbonyl)furan-2-carboxamide (2), and N-(Thiophene-2-ylmethyl)furan-2-carboxamide (3) were investigated the enzyme kinetic studies by urease, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The inhibition constant (Ki) of Compound (CPD)3 by AChE was determined as 0.10 mM, and the Ki value by BChE was determined as 0.07 mM. In comparison, the Ki value of CPD1 by urease was determined as 0.10 mM. These CPDs were examined for antioxidant activity by the DPPH˙ scavenging method. CPD3 exhibited 98.93% DPPH scavenging activity compared to ascorbic acid, the positive control group. Furthermore, the DNA-protective activities of the compounds were investigated, and the DNA protection activity of CPD1 was observed to be 78%. The findings suggest that thiophene/furan carboxy amide-containing CPD1 and CPD3 might be exploited as potential structures for evaluating pharmaceuticals with greater potency.

Dose-Dependent Attenuation of the Efficacy of Clitoria ternatea by Cobalt Oxide Nanoparticles Against Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is a metabolic disorder caused by insulin deficiency, insulin resistance, genetic alterations, and oxidative stress. The high glucose levels may impair the functioning of nerve cells, leading to neurodegenerative diseases, including cognitive impairment. Clitoria ternatea has various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects. The present study evaluates the efficacy of fresh flower aqueous extract of Clitoria ternatea against diabetes-induced cognitive impairment. The challenges in delivering drugs targeting the brain possess the limitations of crossing the blood-brain barrier. Metal nanoparticles are considered the most reliable brain drug delivery systems. Considering the neurotoxicity of cobalt oxide, whether it can be used to improve brain delivery is also evaluated. Cobalt oxide nanoparticles (Co3O4 NPs) of fresh flower aqueous extract of Clitoria ternatea are prepared by green synthesis and characterized. The effect of these nanoparticles is compared with Clitoria ternatea extract against Streptozotocin (STZ)-induced cognitive impairment. The behavioral, biochemical, in vivo antioxidant, total thiol content, estimation of proinflammatory cytokines, acetylcholine esterase, and nitrite levels in the brain of STZ-induced diabetic rats revealed that cobalt oxide nanoparticles showed neurotoxicity, whereas C. ternatea showed neuroprotective effect and also improved the cognitive function. The lower dose of cobalt oxide nanoparticles of C. ternatea (2mg/kg) exhibited a neuroprotective and cognition improvement effect. However, the higher dose (4mg/kg) of cobalt oxide nanoparticles of C. ternatea showed a neurotoxic effect. Since Co3O4 NPs are neuroprotective at low doses, they can be used for neuroprotective actions. However, dose optimization studies are required.

Benzalkonium chloride induced acute toxicity and its multifaceted implications on growth, hematological metrics, biochemical profiles, and stress-responsive biomarkers in tilapia (Oreochromis mossambicus).

This study aimed to investigate the toxic effects of benzalkonium chloride (BAC) on Oreochromis mossambicus, a freshwater fish species. Probit analysis was used to determine the lethal concentration (LC50) of BAC for different exposure periods (24, 48, 72, and 96h). The viability of fish exposed to BAC was assessed using the general threshold survival models (GUTS) and confirmed with relevant datasets to evaluate model accuracy. Experimental groups of fish were exposed to BAC concentrations equivalent to 10% and 20% of the 96-h LC50 for 45days. The study revealed significant alterations in various parameters during sublethal BAC exposure. These effects included decreased specific growth rate (SGR), red blood cell count (RBC), hemoglobin (Hb) concentration, hematocrit (Ht) value, plasma protein, and albumin levels, as well as acetylcholinesterase (AChE) activities in both gills and liver. Additionally, an increase in gastrosomatic index (GSI), feed conversion ratio (FCR), plasma glucose and creatinine concentrations, alanine aminotransferase (ALT), aspartate aminotransferase (AST) enzymatic activities, catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were observed in the exposed fish's gills and liver. Furthermore, the study found that glutathione S-transferase (GST) and glutathione peroxidase (GPx) levels initially increased and then decreased in both gills and liver after exposure to BAC. Correlation matrix analysis, multivariate multiple regression (MMR), canonical correspondence analysis (CCA), integrated biomarker response (IBR), and biomarker response index (BRI) were utilized to assess the impact of BAC on fish, highlighting significant effects on multiple biomarkers in O. mossambicus following surfactant exposure. Thus, the study provides valuable insights into the toxic effects of BAC on this fish species, emphasizing the importance of monitoring such pollutants in aquatic environments.

Morin attenuated the global cerebral ischemia via antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats.

Global cerebral ischemia is one of the major causes of memory and cognitive impairment. Hyperactivation of acetylcholine esterase (AChE), oxidative stress, and inflammation are reported to cause memory and cognitive impairment in global cerebral ischemia. Morin, a flavonoid, is reported to have neuroprotective properties through its antioxidant and anti-inflammatory in multiple neurological diseases. However, its neuroprotective effects and memory and cognition enhancement have not yet been investigated. In the present study, we have determined the memory and cognition, and neuroprotective activity of Morin in bilateral common carotid artery occlusion and reperfusion (BCCAO/R) in Wistar rats. We found that Morin treatment significantly improved motor performance like grip strength and rotarod. Further, Morin improved memory and cognition in BCCAO rats by decreasing the AchE enzyme activity and enhancing the acetylcholine (Ach) levels. Additionally, Morin exhibited neuroprotection by ameliorating oxidative stress, neuroinflammation, and apoptosis in BCCAO rats. These findings confirm that Morin could enhance memory and cognition by ameliorating AchE activity, oxidative stress, neuroinflammation, and apoptosis in global cerebral ischemia. Therefore, Morin could be a promising neuroprotective and memory enhancer against global cerebral ischemic injury.

Neuroprotective Effects of Phenolic Constituents from Drynariae Rhizoma.

This study aimed to provide scientific data on the anti-Alzheimer's disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and monoamine oxidase-B (MAO-B) confirmed their significant inhibitory activities. The DR extract was confirmed to have BACE1-inhibitory activity, and the ethyl acetate and butanol fractions were found to inhibit all AD-related enzymes, including BACE1, AChE, BChE, and MAO-B. Among the isolated phenolic compounds, compounds (2) caffeic acid 4-O-β-D-glucopyranoside, (6) kaempferol 3-O-rhamnoside 7-O-glucoside, (7) kaempferol 3-o-b-d-glucopyranoside-7-o-a-L-arabinofuranoside, (8) neoeriocitrin, (9) naringin, and (10) hesperidin significantly suppressed AD-related enzymes. Notably, compounds 2 and 8 reduced soluble Amyloid Precursor Protein β (sAPPβ) and β-secretase expression by over 45% at a concentration of 1.0 μM. In the thioflavin T assay, compounds 6 and 7 decreased Aβ aggregation by approximately 40% and 80%, respectively, and degraded preformed Aβ aggregates. This study provides robust evidence regarding the potential of DR as a natural therapeutic agent for AD, highlighting specific compounds that may contribute to its efficacy.

Real time monitoring of nerve agent mimics: Novel solid state emitter for enhanced precision and reliability

Chemical nerve agents are hazardous compounds that terrorists can exploit to pose a significant threat to public safety and national security. The nucleophilic behaviour of these agents enables their interaction with acetyl cholinesterase in the body, leading to paralysis and potentially fatal consequences. Therefore, developing robust and efficient detection methods for these agents is crucial for preventing their misuse. In this manuscript, (E)-12-(1-hydrazineylideneethyl)benzo[f]pyrido[1,2-a]indole-6,11-dione (HBID) is developed as a novel colorimetric and fluorometric probe for the detection of specific chemical nerve agent simulants in both liquid and vapor phase. HBID reacts rapidly with diethyl chlorophosphate (DCP), a common nerve agent simulant, leading to a significant increase in the fluorescence intensity. Under optimized conditions, HBID exhibits high sensitivity, good recyclability, fast response and low limit of detection (0.092 µM). NMR and mass spectral studies suggest that the reaction involves the nucleophilic addition of HBID to DCP, forming a phosphate ester. Additionally, the developed sensor demonstrates viscosity-sensitive AIE phenomena thus greatly expanding its potential applications in biological systems. This sensitivity enables precise detection and visualization of viscosity changes within cellular environments, making the sensor an invaluable tool for studying complex biological processes. The developed probe also detects pH within biologically relevant range (4–6). In practical applications, the probe-treated strips efficiently detected DCP vapor in real time, showing a noticeable fluorescence response. Further, the probe has a strong potential to detect the presence of DCP in the soil samples.

Sturgeon (Acipenser schrenckii) spinal cord peptides: Antioxidative and acetylcholinesterase inhibitory efficacy and mechanisms

Providing antioxidants and targeting acetylcholinesterase (AChE) are key strategies in treating neurocognitive dysfunction. In this study, bioactive sturgeon (Acipenser schrenckii) spinal cord peptides (SSCPs) with antioxidant and AChE inhibitory potency were extracted and separated from sturgeon spinal cord by enzymatic hydrolysis and ultrafiltration, and targeted peptide PGGW was screened via computer simulated molecular docking. Further, the molecular dynamic interactions of the PGGW with superoxide dismutase (SOD) and AChE were analyzed, and the protective effect of PGGW on glutamate-induced PC12 cells in vitro was evaluated. The <3 kDa fraction of SSCPs displays the most potent antioxidative efficacy (1 mg/mL, DPPH•: 89.07%, ABTS+: 76.35%). Molecular dynamics simulation showed that PGGW was stable within AChE and tightly bound to residues SER203, PHE295, ILE294 and TRP236. When combined with SOD, the indole group of PGGW was stuck inside SOD, but the tail chain PGG fluctuated greatly outside. Surface plasmon resonance demonstrated that PGGW has a high binding affinity for AChE (KD = 1.4 mM) and 0.01 mg/mL PGGW provided good protection against glutamate-induced apoptosis. The findings suggest a promising strategy for drug research on neurodegenerative diseases.