Статті в журналах: "Acetylcholinesterase – analyse"

1

Kamal, Mohammad A., M. Reale, and Abdulaziz A. Al-Jafari. "Multiple Approaches to Analyse the Data for Rat Brain Acetylcholinesterase Inhibition by Cyclophosphamide." Neurochemical Research 35, no. 10 (July 21, 2010): 1501–9. http://dx.doi.org/10.1007/s11064-010-0199-y.

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Singh, Manju. "Studies on Effects of Chronic Exposure of Some Organophosphates to Catla catla (HaM.)." UTTAR PRADESH JOURNAL OF ZOOLOGY 44, no. 13 (July 13, 2023): 131–41. http://dx.doi.org/10.56557/upjoz/2023/v44i133552.

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The present study deals with the long-term toxic effects of the lowest sub-lethal concentration of dimethoate and malathion on a freshwater fish Catla catla. Toxicity is measured in terms of inhibition in acetylcholinesterase activity and fish behaviour. Technical grades of dimethoate (30 EC) and malathion (50 EC) were used for the present study. LC50 values for 96 hours were calculated for both pesticides. The lowest sublethal concentration (1/5 of LC50) of both pesticides was taken for chronic exposure. As organophosphates are potent inhibitors of acetylcholinesterase (AChE) activity, the AChE activity was estimated by the method of Metcalf (1957) in the brain and liver tissue of the test fishes to evaluate chronic toxicity. The fish were observed regularly to analyse the changes in behaviour. A significant increase in inhibition of acetylcholinesterase activity was observed. Experimental fishes exhibited a decreased rate of opercular movement, loss of balance, excessive mucous secretion, erratic swimming, and increased surfacing with increasing exposure time. Probable reasons for these alterations have been discussed in detail.

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3

Podolska, Magdalena, and Dorota Napierska. "Acetylcholinesterase activity in hosts (herring Clupea harengus) and parasites (Anisakis simplex larvae) from the southern Baltic." ICES Journal of Marine Science 63, no. 1 (January 1, 2006): 161–68. http://dx.doi.org/10.1016/j.icesjms.2005.08.001.

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Abstract This study compares the acetylcholinesterase (AChE) activity of herring Clupea harengus infected with Anisakis simplex larvae and non-infected individuals caught in coastal waters of the southern Baltic. Acetylcholinesterase activity was measured spectrophotometrically. Generalized linear models were applied to analyse the dependence of AChE activity on the area of sampling and the biological parameters of fish and their parasites. The AChE activity of herring was higher in samples from the western and central coasts (regarded as “clean” waters) than in fish caught in the semi-enclosed areas of the Gulf of Gdańsk and Vistula Lagoon (regarded as “polluted” sites). The opposite relationship was noted in the activity of AChE extracted from A. simplex larvae. In male hosts, the parasitic AChE activity was markedly higher than in the females in all examined areas.

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ROSENBAUM, ENRIQUE ARTURO, ANA MARÍA PECHEN DE D'ANGELO, ROSA MARÍA BERGOC, and ANDRÉS VENTURINO. "MODELLING ACETYLCHOLINESTERASE KINETICS: THE IDENTIFIABILITY PROBLEM IN PARAMETER ESTIMATION." Journal of Biological Systems 07, no. 01 (March 1999): 95–111. http://dx.doi.org/10.1142/s0218339099000097.

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Acetylcholinesterase (E.C. 3.1.1.7) is a typical hydrolase showing substrate inhibition. Classical works stated a two-step kinetics for the catalytic mechanism. We analyse here a full interacting model for the substrate bound to an inhibitory site different to the catalytic one, in agreement with current tridimensional data. A mixed model derived from equilibrium-steady state analysis fits fairly well to experimental data. We conclude that both catalytic steps are susceptible of partial inhibition, with 15% of remaining activity for substrate saturated enzyme. Indeed, substrate inhibition would be preferentially exerted on one of the catalytic steps, leading to particular cases which fit to data as well. The parametric identity among the mathematical expressions from restricted models disables identifiability of kinetic constants solely by fitting to data. Thus, additional information is required from other experimental approaches. Based on the cited closeness between both rate constants for the substrate acetylthiocholine, dissociation constants at the catalytic and inhibitory sites are estimated in ~ 63 μM and ~ 0.35 mM respectively, while interaction between binding sites might enhance the latter up to 16 mM. We also emphasise the relevance of considering substrate inhibition in kcat extrapolations even at low substrate concentrations. Finally, we are able to predict total acetylated enzyme values in the order of those done from direct experimental measurements.

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KOVARIK, Zrinka, Zoran RADIĆ, Harvey A. BERMAN, Vera SIMEON-RUDOLF, Elsa REINER, and Palmer TAYLOR. "Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates." Biochemical Journal 373, no. 1 (July 1, 2003): 33–40. http://dx.doi.org/10.1042/bj20021862.

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A series of eight double and triple mutants of mouse acetylcholinesterase (AChE; EC 3.1.1.7), with substitutions corresponding to residues found largely within the butyrylcholinesterase (BChE; EC 3.1.1.8) active-centre gorge, was analysed to compare steady-state kinetic constants for substrate turnover and inhibition parameters for enantiomeric methylphosphonate esters. The mutations combined substitutions in the acyl pocket (Phe295→Leu and Phe297→Ile) with the choline-binding site (Tyr337→Ala and Phe338→Ala) and with a side chain (Glu202→ Gln) N-terminal to the active-site serine, Ser203. The mutations affected catalysis by increasing Km and decreasing kcat, but these constants were typically affected by an order of magnitude or less, a relatively small change compared with the catalytic potential of AChE. To analyse the constraints on stereoselective phosphonylation, the mutant enzymes were reacted with a congeneric series of SP- and RP-methylphosphonates of known absolute stereochemistry. Where possible, the overall reaction rates were deconstructed into the primary constants for formation of the reversible complex and intrinsic phosphonylation. The multiple mutations greatly reduced the reaction rates of the more reactive SP-methylphosphonates, whereas the rates of reaction with the RP-methylphosphonates were markedly enhanced. With the phosphonates of larger steric bulk, the enhancement of rates for the RP enantiomers, coupled with the reduction of the SP enantiomers, was sufficient to invert markedly the enantiomeric preference. The sequence of mutations to enlarge the size of the AChE active-centre gorge, resembling in part the more spacious gorge of BChE, did not show an ordered conversion into BChE reactivity as anticipated for a rigid template. Rather, the individual aromatic residues may mutually interact to confer a distinctive stereospecificity pattern towards organophosphates.

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Moreta, Marta Pérez-Gómez, Natalia Burgos-Alonso, María Torrecilla, José Marco-Contelles, and Cristina Bruzos-Cidón. "Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer’s Disease. Review of Reviews." Biomedicines 9, no. 11 (November 15, 2021): 1689. http://dx.doi.org/10.3390/biomedicines9111689.

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Alzheimer’s disease (AD) is the most common form of dementia over the age of 65. It is estimated that 115.4 million people will be affected by AD by 2050. Acetylcholinesterase inhibitors (AChEI) are the only available and approved treatment for AD. The aim of the present study was to analyse the evidence on the efficacy of the AChEI in the treatment of cognitive symptoms of Alzheimer’s disease. For that purpose, a review of review of the systematic reviews (SRs) on this topic was carried out by Web of Science, PubMed, and The Cochrane Library, among others, were searched until 24 September 2021. Thirteen of the 1773 articles evaluated the efficacy of AChEI on cognitive function and/or general condition and/or behavioural disturbances of patients with mild to moderate AD. Methodological quality and risk of bias were rated using the ROBIS scale. The quality of the identified studies was high for nine of them, unclear for two, and finally only in two of the 13 studies did we detect low quality. Overall, AChEI showed very low efficacy in improving cognition in patients with mild to moderate AD. Better results were obtained in improving global state, with donepezil being the most effective treatment. No improvements in behavioural disturbances were found. Few high-quality reviews provide clear evidence of the effects of AChEI on cognition, global change, behaviour, and mortality. The data suggest that AChEI stabilize or slow cognitive deterioration, improving global status. In addition, data indicate that the use of AChEI decreases mortality in patients with mild to moderate AD. However, there is no evidence that they improve patient behaviour. Donepezil is the best therapeutic alternative at a dose of 10 mg/day.

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Anju, T. R., and C. S. Paulose. "Striatal cholinergic functional alterations in hypoxic neonatal rats: Role of glucose, oxygen, and epinephrine resuscitation." Biochemistry and Cell Biology 91, no. 5 (October 2013): 350–56. http://dx.doi.org/10.1139/bcb-2012-0102.

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Molecular processes regulating cholinergic functions play an important role in the control of respiration under hypoxia. Cholinergic alterations and its further complications in respiration due to hypoxic insult in neonatal rats and the effect of glucose, oxygen, and epinephrine resuscitation was evaluated in the present study. Receptor binding and gene expression studies were done in the corpus striatum to analyse the changes in total muscarinic receptors, muscarinic M1, M2, M3 receptors, and the enzymes involved in acetylcholine metabolism, choline acetyltransferase and acetylcholinesterase. Neonatal hypoxia decreased total muscarinic receptors with reduced expression of muscarinic M1, M2, and M3 receptor genes. The reduction in acetylcholine metabolism is indicated by the downregulated choline acetyltransferase and upregulated acetyl cholinesterase expression. These cholinergic disturbances were reversed to near control in glucose-resuscitated hypoxic neonates. The adverse effects of immediate oxygenation and epinephrine administration are also reported. The present findings points to the cholinergic alterations due to neonatal hypoxic shock and suggests a proper resuscitation method to ameliorate these striatal changes.

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8

Suciati, Suciati, Erlinda Rhohmatul Laili, Hamizah Haula, Lidya Tumewu, Nitra Nuengchamnong, Nungruthai Suphrom, and Aty Widyawaruyanti. "Phytoconstituents, antioxidant, and cholinesterase inhibitory activities of the leaves and stem extracts of Artocarpus sericicarpus." Pharmacia 71 (February 19, 2024): 1–8. http://dx.doi.org/10.3897/pharmacia.71.e112499.

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The study aimed to investigate the antioxidant and cholinesterase inhibitory activities of the leaves and stems of Artocarpus sericicarpus and to analyse the phenolic compounds in the extracts. The modified Ellman’s method was used to determine the cholinesterase inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The antioxidant properties were evaluated using DPPH and ABTS methods. The total phenolic content (TPC) was measured by spectrometric assay, and compound identification was carried out by LC-MS/MS analysis. The results showed that the leaf and stem extracts of A. sericicarpus exerted significant inhibitory effects against AChE and BChE, as well as antioxidant activities. The stem ethanolic extract exhibited the highest potency against AChE and BChE with IC50 values of 5.81 and 11.46 µg/mL, respectively. The leaf and stem ethanolic extracts gave higher antioxidant activities and TPC compared to the water-based extracts. The LC-MS/MS analysis indicated the presence of phenolic compounds, such as flavones, flavonols, flavanones, prenylated chalcones, and xanthones in the extracts.

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Abd Rashed, Aswir, Ahmad Zuhairi Abd Rahman, and Devi Nair Gunasegavan Rathi. "Essential Oils as a Potential Neuroprotective Remedy for Age-Related Neurodegenerative Diseases: A Review." Molecules 26, no. 4 (February 19, 2021): 1107. http://dx.doi.org/10.3390/molecules26041107.

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Despite the improvements in life expectancy, neurodegenerative conditions have arguably become the most dreaded maladies of older people. The neuroprotective and anti-ageing potentials of essential oils (EOs) are widely evaluated around the globe. The objective of this review is to analyse the effectiveness of EOs as neuroprotective remedies among the four common age-related neurodegenerative diseases. The literature was extracted from three databases (PubMed, Web of Science and Google Scholar) between the years of 2010 to 2020 using the medical subject heading (MeSH) terms “essential oil”, crossed with “Alzheimer’s disease (AD)”, “Huntington’s disease (HD)”, “Parkinson’s disease (PD)” or “amyotrophic lateral sclerosis (ALS)”. Eighty three percent (83%) of the studies were focused on AD, while another 12% focused on PD. No classifiable study was recorded on HD or ALS. EO from Salvia officinalis has been recorded as one of the most effective acetylcholinesterase and butyrylcholinesterase inhibitors. However, only Cinnamomum sp. has been assessed for its effectiveness in both AD and PD. Our review provided useful evidence on EOs as potential neuroprotective remedies for age-related neurodegenerative diseases.

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Pham, Van Dung, Tuan Anh To, Cynthia Gagné-Thivierge, Manon Couture, Patrick Lagüe, Deqiang Yao, Marie-Ève Picard, et al. "Structural insights into the putative bacterial acetylcholinesterase ChoE and its substrate inhibition mechanism." Journal of Biological Chemistry 295, no. 26 (May 5, 2020): 8708–24. http://dx.doi.org/10.1074/jbc.ra119.011809.

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Mammalian acetylcholinesterase (AChE) is well-studied, being important in both cholinergic brain synapses and the peripheral nervous systems and also a key drug target for many diseases. In contrast, little is known about the structures and molecular mechanism of prokaryotic acetylcholinesterases. We report here the structural and biochemical characterization of ChoE, a putative bacterial acetylcholinesterase from Pseudomonas aeruginosa. Analysis of WT and mutant strains indicated that ChoE is indispensable for P. aeruginosa growth with acetylcholine as the sole carbon and nitrogen source. The crystal structure of ChoE at 1.35 Å resolution revealed that this enzyme adopts a typical fold of the SGNH hydrolase family. Although ChoE and eukaryotic AChEs catalyze the same reaction, their overall structures bear no similarities constituting an interesting example of convergent evolution. Among Ser-38, Asp-285, and His-288 of the catalytic triad residues, only Asp-285 was not essential for ChoE activity. Combined with kinetic analyses of WT and mutant proteins, multiple crystal structures of ChoE complexed with substrates, products, or reaction intermediate revealed the structural determinants for substrate recognition, snapshots of the various catalytic steps, and the molecular basis of substrate inhibition at high substrate concentrations. Our results indicate that substrate inhibition in ChoE is due to acetate release being blocked by the binding of a substrate molecule in a nonproductive mode. Because of the distinct overall folds and significant differences of the active site between ChoE and eukaryotic AChEs, these structures will serve as a prototype for other prokaryotic acetylcholinesterases.

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Elgueta, Sebastian, Marcela Valenzuela, Marcela Fuentes, Pilar E. Ulloa, Cecilia Ramos, Arturo Correa, and Sebastian Molinett. "Analysis of Multi-Pesticide Residues and Dietary Risk Assessment in Fresh Tomatoes (Lycopersicum esculentum) from Local Supermarkets of the Metropolitan Region, Chile." Toxics 9, no. 10 (October 6, 2021): 249. http://dx.doi.org/10.3390/toxics9100249.

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In recent years, the official authorities in Chile have reported transgressions in the maximum residue levels of pesticides in fresh vegetables. There is no official information about traceability, pesticide levels, and potential health risks. The aim of this study was to analyse pesticide residues and their corresponding dietary risk assessments in tomatoes from supermarkets in the Metropolitan Region. Pesticides were extracted using the Quick, Easy, Cheap, Effective, Rugged and Safe, QuEChERS method, and their concentrations were determined by using chromatography with HPLC-FL/UV and GC-MS/ECD/NPD, following the Analytical Quality Control and Method Validation Procedures for Pesticides Residues Analysis in Food and Feed, SANTE guide and ISO 17025:2017 standard. In addition, a dietary risk assessment was carried out by comparing Chilean data to international references. The results reported that 9% of the samples had pesticide residue levels above the maximum residue levels permitted in Chile. All the scenarios evaluated revealed the highest estimated daily intake and hazard quotients for methamidophos and chlorpyrifos. Both the active substances used were acetylcholinesterase inhibitors and were neurotoxic under chronic risk assessment. The results showed the highest chronic hazard index in the Chilean scenario for all age groups and genders. The evidence obtained revealed that methamidophos, methomyl, and chlorpyrifos should be restricted for their use in Chilean agriculture.

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Dono, Danar, Neneng S. Widayani, Safri Ishmayana, Yusup Hidayat, Fitri Widiantini, and Ceppy Nasahi. "Resistance of Nilaparvata lugens to Fenobucarb and Imidacloprid and Susceptibility to Neem Oil Insecticides." HAYATI Journal of Biosciences 29, no. 2 (January 26, 2022): 234–44. http://dx.doi.org/10.4308/hjb.29.2.234-244.

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This study aims to monitor and determine the level of resistance of N. lugens to fenobucarb and imidacloprid, to analyse of the specific activities of asetylcholinesterase, Glutation S-Transferase, esterase, and to determine sensitivity of resistant N. lugens to the neem oil. Resistance tests were conducted on a field population from Cipunagara, Subang, West Java, Indonesia, and a standard population originating from Banyuwangi, East Java, that was obtained from the Indonesian Center for Rice Research. Synthetic and neem Insecticides were applied using the leaf-stem dipping method. The resistance ratio obtained by comparing the LC50 value of the field population with the standard. The test insects were considered to be resistant to synthetic insecticide if they had a resistance ratio (RR) of more than 4, indicated resistance if RR ≥1, and susceptible to neem if has RR <1. The results of the research showed that the N. lugens population of Cipunagara indicated resistance to fenobucarb (RR = 2.43), while it was clearly resistance to imidacloprid (RR = 13.95). Specific activities of the acetylcholinesterase and Glutathione S-Transferase of the N. lugens Cipunagara populations were higher than the standard, while the esterase specific activity was lower. These two enzymes are responsible for the resistance of N. lugens to fenobucarb and imidacloprid. Nevertheless, the N. lugens population of Cipunagara was susceptible to neem (RR <1) that never been reported before. Therefore, it is important to know the change in the sensitivity of the target and the metabolic pathway of the insecticide used to manage insect resistance.

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Belzunces, L. P., J. P. Toutant, and M. Bounias. "Acetylcholinesterase from Apis mellifera head. Evidence for amphiphilic and hydrophilic forms characterized by Triton X-114 phase separation." Biochemical Journal 255, no. 2 (October 15, 1988): 463–70. http://dx.doi.org/10.1042/bj2550463.

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The polymorphism of bee acetylcholinesterase was studied by sucrose-gradient-sedimentation analysis and non-denaturing electrophoretic analysis of fresh extracts. Lubrol-containing extracts exhibited only one form, which sedimented at 5 S when analysed on high-salt Lubrol-containing gradients and 6 S when analysed on low-salt Lubrol-containing gradients. The 5 S/6 S form aggregated upon removal of the detergent when sedimented on detergent-free gradients and was recovered in the detergent phase after Triton X-114 phase separation. Thus the 5 S/6 S enzyme corresponds to an amphiphilic acetylcholinesterase form. In detergent-free extracts three forms, whose apparent sedimentation coefficients are 14 S, 11 S and 7 S, were observed when sedimentations were performed on detergent-free gradients. Sedimentation analyses on detergent-containing gradients showed only a 5 S peak in high-salt detergent-free extracts and a 6 S peak, with a shoulder at about 7 S, in low-salt detergent-free extracts. Electrophoretic analysis in the presence of detergent demonstrated that the 14 S and 11 S peaks corresponded to aggregates of the 5 S/6 S form, whereas the 7 S peak corresponded to a hydrophilic acetylcholinesterase form which was recovered in the aqueous phase following Triton X-114 phase separation. The 5 S/6 S amphiphilic form could be converted into a 7.1 S hydrophilic form by phosphatidylinositol-specific phospholipase C digestion.

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Kovarik, Zrinka, Maja Čalić, Goran Šinko, and Anita Bosak. "Structure-Activity Approach in the Reactivation of Tabun-Phosphorylated Human Acetylcholinesterase with Bispyridinium para-Aldoximes." Archives of Industrial Hygiene and Toxicology 58, no. 2 (June 1, 2007): 201–9. http://dx.doi.org/10.2478/v10004-007-0013-7.

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Structure-Activity Approach in the Reactivation of Tabun-Phosphorylated Human Acetylcholinesterase with Bispyridinium para-AldoximesWe investigated interactions of bispyridinium para-aldoximes N,N'-(propano)bis(4-hydroxyiminomethyl) pyridinium bromide (TMB-4), N,N'-(ethano)bis(4-hydroxyiminomethyl)pyridinium methanosulphonate (DMB-4), and N,N'-(methano)bis(4-hydroxyiminomethyl)pyridinium chloride (MMB-4) with human erythrocyte acetylcholinesterase phosphorylated by tabun. We analysed aldoxime conformations to determine the flexibility of aldoxime as an important feature for binding to the acetylcholinesterase active site. Tabun-inhibited human erythrocyte acetylcholinesterase was completely reactivated only by the most flexible bispyridinium aldoxime - TMB-4 with a propylene chain between two rings. Shorter linkers than propylene (methylene or ethylene) as in MMB-4 and DMB-4 did not allow appropriate orientation in the active site, and MMB-4 and DMB-4 were not efficient reactivators of tabun-phosphorylated acetylcholinesterase. Since aldoximes are also reversible inhibitors of native acetylcholinesterase, we determined dissociation constants and their protective index against acetylcholinesterase inactivation by tabun.

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Imam, Aminu, Barakat Oyindamola Salaudeen, Aboyeji Lukuman Oyewole, Asma'u Shehu Muhammad, Christianah Oyegbola, Rukayat Jaji-Sulaimon, Fatimo Ajoke Sulaimon, Adam Moyosore Afodun, and Moyosore Salihu Ajao. "Chlorpyrifos impaired cerebellar oxidative and cholinesterase activities in rats: Mitigating efficacy of Nigella sativa Oil." Nepal Journal of Neuroscience 18, no. 2 (June 1, 2021): 15–22. http://dx.doi.org/10.3126/njn.v18i2.34525.

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Background: Motor dysfunctions are some of the characteristic symptoms of organophosphate (OP) poisoning and they have been associated with decreased levels of cholinesterase inhibition within motor areas of the brain. Objectives: The current study aims to investigate the potential neuroprotective effects of Nigella sativa oil (NSO) in alleviating chlorpyrifos (CPF) induced toxicity in the cerebella and motor cortices of the rat brains using combined behavioural, biochemical and histochemical methods. Methods: Thirty-two rats were randomly divided into four groups (eight rats per group), exposed to 1ml/kg of normal saline, 14.9 mg/kg of CPF, 14.9 mg/kg of CPF plus 1ml/kg of NSO and 1ml/kg of NSO respectively for 14 consecutive days. The rats were each exposed to a single trial of the Open Field Test (OFT) on day 13 of the experiment. This experimental test measured locomotor activity levels (line crossing frequency (LCF)) and exploratory (rearing frequency (RF)) activities in the rats studied. The rats were euthanized on day 15 of the experiment and the brains were subsequently excised. The cerebella cortices of five brains were removed and homogenised to analyse for total reactive oxygen species (ROS), nitric oxide (NO) levels and acetylcholinesterase (AChE) activity. The motor and cerebella cortices from three other brains in each group were processed for histology (Nissl stain) and proliferative activity (Ki67 immunohistochemistry). Results: Rats exposed to CPF experienced a significant increase in cerebella NO and ROS levels, depletion in AChE activity, neurogenic cells loss and subsequent reduction in locomotor and exploratory behaviours respectively (LCF and RF). However, interventional treatment with NSO depleted markers of oxidative damage (NO and ROS), reduced AChE inhibition, preserved neurogenic (Ki67) cells distribution and motor functions. Conclusion: These results demonstrate the potential efficacy of NSO in OP poisoning and the roles of neurogenic and oxidative functions in the pathophysiology and treatment of motor dysfunction in OP neurotoxicity.

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Niu, Bing, Manman Zhao, Qiang Su, Mengying Zhang, Wei Lv, Qin Chen, Fuxue Chen, Dechang Chu, Dongshu Du, and Yuhui Zhang. "2D-SAR and 3D-QSAR analyses for acetylcholinesterase inhibitors." Molecular Diversity 21, no. 2 (March 9, 2017): 413–26. http://dx.doi.org/10.1007/s11030-017-9732-0.

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Vanderlaan, Martin, Robert Lotti, Gordon Siek, Dixie King, and Mirta Goldstein. "Perfusion immunoassay for acetylcholinesterase: analyte detection based on intrinsic activity." Journal of Chromatography A 711, no. 1 (September 1995): 23–31. http://dx.doi.org/10.1016/0021-9673(95)00059-v.

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Tuzimski, Tomasz, and Anna Petruczynik. "Application of HPLC-DAD for In Vitro Investigation of Acetylcholinesterase Inhibition Activity of Selected Isoquinoline Alkaloids from Sanguinaria canadensis Extracts." Molecules 26, no. 1 (January 5, 2021): 230. http://dx.doi.org/10.3390/molecules26010230.

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Isoquinoline alkaloids may have a wide range of pharmacological activities. Some of them have acetylcholinesterase activity inhibition. Nowadays, neurodegenerative disorders such as Alzheimer’s disease have become a serious public health problem. Searching for new effective compounds with inhibited acetylcholinesterase activity is one of the most significant challenges of modern scientific research. The aim of this study was the in vitro investigation of acetylcholinesterase activity inhibition of extracts obtained from Sanguinaria canadensis collected before, during and after flowering. The acetylcholinesterase activity inhibition of these extracts has not been previously tested. The aim was also to quantify selected alkaloids in the investigated extracts by high performance liquid chromatography (HPLC). The analyses of alkaloid content were performed using HPLC in reversed phase (RP) mode using Polar RP column and mobile phase containing acetonitrile, water and ionic liquid (IL). The acetylcholinesterase activity inhibition of the tested plant extracts and respective alkaloid standards were examined using high performance liquid chromatography with diode-array detector (HPLC-DAD) for the quantification of 5-thio-2-nitro-benzoic acid, which is the product of the reaction between the thiocholine (product of the hydrolysis of acetylthiocholine reaction) with Ellman reagent. The application of the HPLC method allowed for elimination of absorption of interfering components, for example, alkaloids such as sanguinarine and berberine. It is revealed that the HPLC method can be successfully used for the evaluation of the acetylcholinesterase inhibitory activity in samples such as plant extracts, especially those containing colored components adsorbing at wavelength in the range 405–412 nm. The acetylcholinesterase inhibition activity synergy of pairs of alkaloid standards and mixture of all investigated alkaloids was also determined. Most investigated alkaloids and all Sanguinaria canadensis extracts exhibited very high acetylcholinesterase activity inhibition. IC50 values obtained for alkaloid standards were from 0.36 for berberine to 23.13 µg/mL for protopine and from 61.24 to 89.14 µg/mL for Sanguinaria canadensis extracts. Our investigations demonstrated that these plant extracts can be recommended for further in vivo experiments to confirm their acetylcholinesterase activity inhibition.

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Mason, H. J., C. Sams, A. J. Stevenson, and R. Rawbone. "Rates of spontaneous reactivation and aging of acetyicholinesterase in human erythrocytes after inhibition by organophosphorus pesticides." Human & Experimental Toxicology 19, no. 9 (September 2000): 511–16. http://dx.doi.org/10.1191/096032700667340089.

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The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (RjR2) and diethoxy substituted (RjR2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology. A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure.

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Rutnakornpituk, Boonjira, Jantra Jantrapirom, Nitra Nuengchamnong, and Filip Kielar. "Identification of Antioxidants and Acetylcholinesterase Inhibitors from Hapaline benthamiana Schott. Using at Line LC-ESI-QTOF MS/MS." Trends in Sciences 20, no. 1 (November 22, 2022): 6202. http://dx.doi.org/10.48048/tis.2023.6202.

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In this work, total phenolics, total flavonoids, antioxidant activity, and acetylcholinesterase inhibition potency of Hapaline benthamiana schott are reported. In addition, the investigation of antioxidant and anti-acetylcholinesterase compounds of this plant coupled to the at line-LC-ESI-QTOF-MS/MS technique is introduced for the first time. The results show that the methanolic extract contains the highest amount of total phenolics, total flavonoids, antioxidant activity, and acetylcholinesterase inhibition activity. The at line-LC-ESI-QTOF-MS/MS technique has provided information on the biological activity of each compound while mass spectrometry provided information on their molecular weights. Based on their mass spectra, 53 compounds were identified with most of them being phenolic, flavonoid, and glycolipid compounds. Seventeen compounds exhibited a strong antioxidant activity ranging between 51.52 - 63.58 % inhibition whereas one compound, namely septentriodine, showed a strong acetylcholinesterase inhibitory effect of more than 50 %. This study indicates that Hapaline benthamiana schott is a source of active compounds containing antioxidant and anti-acetylcholinesterase activities with health benefits. In addition, at line-LC-ESI-QTOF-MS/MS has been shown to be an effective technique for the rapid and simultaneous analyses of antioxidant and anti-acetylcholinesterase compounds in plant extracts. HIGHLIGHTS Investigation of antioxidants and acetylcholinesterase inhibitors from Hapaline benthamiana Schott coupled to at line-LC-ESI-QTOF-MS/MS technique is reported for the first time Fifty-three compounds from methanolic extract were successfully identified Eighteen compounds exhibited strong biological activity This technique is a rapid and valuable tool for the identification of lead compounds in complex extracts and for the investigation of their bioactivity GRAPHICAL ABSTRACT

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Devic, Eric, Dunhai Li, Alain Dauta, Peter Henriksen, Geoffrey A. Codd, Jean-Louis Marty, and Didier Fournier. "Detection of Anatoxin-a(s) in Environmental Samples of Cyanobacteria by Using a Biosensor with Engineered Acetylcholinesterases." Applied and Environmental Microbiology 68, no. 8 (August 2002): 4102–6. http://dx.doi.org/10.1128/aem.68.8.4102-4106.2002.

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ABSTRACT Bioassays are little used to detect individual toxins in the environment because, compared to analytical methods, these assays are still limited by several problems, such as the sensitivity and specificity of detection. We tentatively solved these two drawbacks for detection of anatoxin-a(s) by engineering an acetylcholinesterase to increase its sensitivity and by using a combination of mutants to obtain increased analyte specificity. Anatoxin-a(s), a neurotoxin produced by some freshwater cyanobacteria, was detected by measuring the inhibition of acetylcholinesterase activity. By using mutated enzyme, the sensitivity of detection was brought to below the nanomole-per-liter level. However, anatoxin-a(s) is an organophosphorous compound, as are several synthetic molecules which are widely used as insecticides. The mode of action of these compounds is via inhibition of acetylcholinesterase, which makes the biotest nonspecific. The use of a four-mutant set of acetylcholinesterase variants, two mutants that are sensitive to anatoxin-a(s) and two mutants that are sensitive to the insecticides, allows specific detection of the cyanobacterial neurotoxin.

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22

Addison, R. F. "The use of biological effects monitoring in studies of marine pollution." Environmental Reviews 4, no. 3 (July 1, 1996): 225–37. http://dx.doi.org/10.1139/a96-012.

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Анотація:

Although we usually view marine pollution in terms of the distribution of chemicals, several modern approaches allow us to detect biological responses to contaminants with sensitivity approaching that of analytical chemistry. In this review, I summarize practical field experience of measuring responses to pollution at different levels of biological complexity. I discuss three biochemical measurements (hepatic monooxygenase induction in fish, metallothionein induction, and acetylcholinesterase inhibition), measurements of energy partitioning in bivalve molluscs, and analyses of benthic community structure to assess the impact of marine pollution.Key words: monooxygenases, metallothioneins, acetylcholinesterase, Scope for growth, community structure.

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Bonning, B. C., J. Hemingway, R. Romi, and G. Majori. "Interaction of insecticide resistance genes in field populations of Culex pipiens (Diptera: Culicidae) from italy in response to changing insecticide selection pressure." Bulletin of Entomological Research 81, no. 1 (March 1991): 5–10. http://dx.doi.org/10.1017/s0007485300053177.

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AbstractCulex pipiens Linnaeus larvae were collected from various locations in Italy and colonized as separate strains. These were analysed for elevated nonspecific esterase activity and frequency of altered acetylcholinesterase (AChE) mechanisms of insecticide resistance, and bioassayed, to define the cross-resistance spectra conferred by these to organophosphorus and carbamate insecticides. These mechanisms were further characterized by polyacrylamide gel electrophoresis. Elevated esterase A1 (formerly known as Est 3A) which predominated in C. pipiens from Italy in 1985 had been replaced by two esterases, A2 and B2. Altered acetylcholinesterase was still present at high frequencies. Altered and normal acetylcholinesterase were distinguished by differential mobility on polyacrylamide gel electrophoresis. Levels of insecticide resistance were higher in the Lucca region of Italy than in other areas sampled, in response to intensive use of temephos and to a lesser extent chlor-pyrifos, employed to reduce mosquito biting nuisance to tourists in this area.

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Orduz-Diaz, LL, W. Cely-Veloza, and E. Coy-Barrera. "In-silico analyses of naturally-occurring isoflavones as inhibitors of acetylcholinesterease." Planta Medica 81, S 01 (December 14, 2016): S1—S381. http://dx.doi.org/10.1055/s-0036-1596261.

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25

Katalinić, Maja, Goran Šinko, Nikolina Maček Hrvat, Tamara Zorbaz, Anita Bosak, and Zrinka Kovarik. "Oxime-assisted reactivation of tabun-inhibited acetylcholinesterase analysed by active site mutations." Toxicology 406-407 (August 2018): 104–13. http://dx.doi.org/10.1016/j.tox.2018.05.008.

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26

Giles, K., I. Silman, and J. L. Sussman. "Human acetylcholinesterase II: In vivo expression and tissue distribution via est analyses." Neuroscience Letters 237 (November 1997): S19—S20. http://dx.doi.org/10.1016/s0304-3940(97)90079-3.

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Cheng, Y. H., X. L. Cheng, Z. Radić, and J. A. McCammon. "Acetylcholinesterase: Mechanisms of covalent inhibition of H447I mutant determined by computational analyses." Chemico-Biological Interactions 175, no. 1-3 (September 2008): 196–99. http://dx.doi.org/10.1016/j.cbi.2008.04.044.

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Shadnia, Shahin, Ebrahim Azizi, Rohollah Hosseini, Samideh Khoei, Shamileh Fouladdel, Abdolkarim Pajoumand, Nasser Jalali, and Mohammad Abdollahi. "Evaluation of oxidative stress and genotoxicity in organophosphorus insecticide formulators." Human & Experimental Toxicology 24, no. 9 (September 2005): 439–45. http://dx.doi.org/10.1191/0960327105ht549oa.

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The aim of this study was to evaluate genotoxicity and oxidative stress in workers who formulate organophosphorus (OP) pesticides. In this survey, blood leukocytes and erythrocytes of a group of 21 pesticide formulating workers and an equal number of control subjects were examined for genotoxicity and oxidative stress parameters. The mean comet tail length and mean comet length were used to measure DNA damage. Lipid peroxidation level, catalase, superoxide dismutase (SOD) and glutathione peroxidase activities in erythrocytes were analysed as biomarkers of oxidative stress. In addition, the acetylcholinesterase activity was measured as a biomarker of toxicity. The average duration of employment of workers in the factory was 97 months. Results indicated that chronic exposure (multiple5dose, greater than or equal to 6 months duration) to OP pesticides was associated with increased activities of catalase, SOD and glutathione peroxidase in erythrocytes. The level of lipid peroxidation and acetylcholinesterase activity did not show any significant differences between the two groups. The results also indicated that chronic exposure to OP pesticides was associated with increased DNA damage. It is concluded that human chronic exposure to OP pesticides may result in stimulated antioxidant enzymes and increased DNA damage in the absence of depressed acetylcholinesterase levels. Routine genotoxicity monitoring concomitant to acetylcholinesterase activity in workers occupationally exposed to OP insecticides is suggested.

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Abdulqahar, Fadwa W., Mohammed A. Morgab, Feryal F. Hussein, Yulia Apyantseva, and Tamer M. El-Messery. "In silico analyses of bioactive compounds extracted from ziziphus jujuba using supercritical CO2 extraction: Potential anti-anxiety and anti-Alzheimer’s disease." Bioactive Compounds in Health and Disease 6, no. 10 (October 4, 2023): 215. http://dx.doi.org/10.31989/bchd.v6i10.1180.

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Background: Jujube (Chinese date) is a fruit with a pleasant, sweet taste, traditionally used as sedative to treat insomnia and anxiety. Objective: The study aims to explore the potential of these bioactive compounds in exerting anti-anxiety and anti-Alzheimer's disease effects. Methods: Molecular docking, ADME, and molecular dynamics studies were carried out for the green-extracted phytochemicals against acetylcholinesterase and Beta-amyloid proteins for Anti-Alzheimer’s disease effect and serotonin receptor for anti-anxiety activity. Our results suggest that compound (2,3,6,7-tetramethyl-10-(4-methylphenylsulfonyloxy)-1,4,4.alpha.,5,8,8a.beta.,9.b) showed good binding affinity of -10.3 with acetylcholinesterase (4EY7) as anti-Alzheimer’s disease and the compound andrographolide with serotonin transporter (6VRH) showed binding affinity of -9.7 for anxiety. Compounds with the best docking scores were subjected to molecular dynamic simulations.Results: These compounds revealed the best stability. Conclusion: These findings are promising for manufacturing new functional foods, nutraceuticals, food supplements, and/or pharmaceuticals which may play a good and safe role in treating Alzheimer disease and anxiety. While further biological studies must be carried out, our computational studies suggest that these compounds have potent activity.Keywords: Ziziphus jujuba; Bioactive compounds; Neurological disorders disease; Molecular docking, ADME and Molecular dynamics.

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Altaf, S., F. Muhammad, B. Aslam, and MN Faisal. "Cell membrane enveloped polymeric nanosponge for detoxification of chlorpyrifos poison: In vitro and in vivo studies." Human & Experimental Toxicology 40, no. 8 (February 15, 2021): 1286–95. http://dx.doi.org/10.1177/0960327121993207.

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Organophosphates are highly toxic compounds as they are involved in irreversible inhibition of acetylcholinesterase, causing various neurotoxic effects via acetylcholine accumulation throughout the nervous system. Traditional treatments for organophosphate poisoning are not effective enough to overcome all the toxic effects. There is a need for alternate treatment of life threatening poisoning of organophosphates. For this purpose a biomimetic nanosponge of poly (lactic- co-glycolic acid) is prepared, characterized and analysed as an antidote for organophosphate poisoning. In this nanosponge red blood cell membranes are used for coating poly lactic co-glycolic acid nanoparticles. In vitro studies are conducted to investigate the retention of acetylcholinesterase activity on the prepared nanosponge as well as to assess the scavenging ability of prepared nanosponge for model organophosphate, chlorpyrifos. In vivo studies are conducted to evaluate the detoxification potential of nanosponge in rabbit model, poisoned with chlorpyrifos. Hepatotoxicity and renal toxicity of nanosponge/chlorpyrifos complex is also studied in survived rabbits and the data is analysed statistically.

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Pérez-Aguilar, Benjamín, Jens U. Marquardt, Encarnación Muñoz-Delgado, Rosa María López-Durán, María Concepción Gutiérrez-Ruiz, Luis E. Gomez-Quiroz, and José Luis Gómez-Olivares. "Changes in the Acetylcholinesterase Enzymatic Activity in Tumor Development and Progression." Cancers 15, no. 18 (September 19, 2023): 4629. http://dx.doi.org/10.3390/cancers15184629.

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Acetylcholinesterase is a well-known protein because of the relevance of its enzymatic activity in the hydrolysis of acetylcholine in nerve transmission. In addition to the catalytic action, it exerts non-catalytic functions; one is associated with apoptosis, in which acetylcholinesterase could significantly impact the survival and aggressiveness observed in cancer. The participation of AChE as part of the apoptosome could explain the role in tumors, since a lower AChE content would increase cell survival due to poor apoptosome assembly. Likewise, the high Ach content caused by the reduction in enzymatic activity could induce cell survival mediated by the overactivation of acetylcholine receptors (AChR) that activate anti-apoptotic pathways. On the other hand, in tumors in which high enzymatic activity has been observed, AChE could be playing a different role in the aggressiveness of cancer; in this review, we propose that AChE could have a pro-inflammatory role, since the high enzyme content would cause a decrease in ACh, which has also been shown to have anti-inflammatory properties, as discussed in this review. In this review, we analyze the changes that the enzyme could display in different tumors and consider the different levels of regulation that the acetylcholinesterase undergoes in the control of epigenetic changes in the mRNA expression and changes in the enzymatic activity and its molecular forms. We focused on explaining the relationship between acetylcholinesterase expression and its activity in the biology of various tumors. We present up-to-date knowledge regarding this fascinating enzyme that is positioned as a remarkable target for cancer treatment.

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Lyu, Difei. "Effects of Pesticides on Asthma." Highlights in Science, Engineering and Technology 40 (March 29, 2023): 251–56. http://dx.doi.org/10.54097/hset.v40i.6662.

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It is very necessary to apply pesticides to crops in today's world, given the level of scientific development, so that we can be successfully protected from pests. However, pesticides are a double-edged sword that may both save our lives and take them at the same time. This is especially true when considering the adverse effects that organophosphorus and carbamate pesticides can have on asthma sufferers. Once we have a better understanding of what causes disease, we will be able to develop more effective treatments. For instance, in the not-too-distant future, we may be able to develop medications that can dilute organophosphorus before it has an adverse effect on acetylcholinesterase. In this study, case analysis was used to determine the hypothesis directly through a study, and then to find evidence to analyze and confirm the hypothesis, which is that organophosphorus pesticides can inhibit acetylcholinesterase, thereby causing bronchospasm and triggering asthma. This hypothesis was confirmed by finding evidence that organophosphorus pesticides can inhibit acetylcholinesterase. At the end of this paper, through the course of the study, we arrived at the conclusion that organophosphorus pesticides can block acetylcholinesterase. Therefore, what we need to do is avoid exposing asthma patients to pesticides that include organophosphorus. The findings of this study point the way in the path that the future production of related drunk protection should take. Patients should take precautions against exposure to organophosphorus pesticides by avoiding agricultural land that has been irrigated with these chemicals and thoroughly washing any clothing or produce that has come into possible contact with these chemicals.

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Cuong, To Dao, Tran Manh Hung, Hyoung Yun Han, Hang Sik Roh, Ji-Hyeon Seok, Jong Kwon Lee, Ja Young Jeong, Jae Sue Choi, Jeong Ah Kim, and Byung Sun Min. "Potent Acetylcholinesterase Inhibitory Compounds from Myristica fragrans." Natural Product Communications 9, no. 4 (April 2014): 1934578X1400900. http://dx.doi.org/10.1177/1934578x1400900418.

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The anti-cholinesterase activity was evaluated of the ethyl acetate fraction of the methanol extract of Myristica fragrans Houtt (Myristicaceae) seeds and of compounds isolated from it by various chromatographic techniques. The chemical structures of the compounds were determined from spectroscopic analyses (NMR data). Thirteen compounds (1—13) were isolated and identified. Compound 8 {[(7S)-8′-(4′-hydroxy-3′-methoxyphenyl)-7-hydroxypropyl]benzene-2,4-diol} showed the most effective activity with an IC50 value of 35.1 μM, followed by compounds 2 [(8R,8′S)-7′-(3′,4′-methylenedioxyphenyl)-8,8′-dimethyl-7-(3,4-dihydroxyphenyl)-butane] and 11 (malabaricone C) with IC50 values of 42.1 and 44.0 μM, respectively. This is the first report of significant anticholinesterase properties of M. fragrans seeds. The findings demonstrate that M. fragrans could be used beneficially in the treatment of Alzheimer's disease.

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Arslan, Mehmet Enes, Hasan Türkez, Yasemin Sevim, Harun Selvitopi, Abdurrahim Kadi, Sena Öner, and Adil Mardinoğlu. "Costunolide and Parthenolide Ameliorate MPP+ Induced Apoptosis in the Cellular Parkinson’s Disease Model." Cells 12, no. 7 (March 24, 2023): 992. http://dx.doi.org/10.3390/cells12070992.

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Monoamine oxidase B (MAO-B) is an enzyme that metabolizes several chemicals, including dopamine. MAO-B inhibitors are used in the treatment of Parkinson’s Disease (PD), and the inhibition of this enzyme reduces dopamine turnover and oxidative stress. The absence of dopamine results in PD pathogenesis originating from decreased Acetylcholinesterase (AChE) activity and elevated oxidative stress. Here, we performed a molecular docking analysis for the potential use of costunolide and parthenolide terpenoids as potential MAO-B inhibitors in the treatment of PD. Neuroprotective properties of plant-originated costunolide and parthenolide terpenoids were investigated in a cellular PD model that was developed by using MPP+ toxicity. We investigated neuroprotection mechanisms through the analysis of oxidative stress parameters, acetylcholinesterase activity and apoptotic cell death ratios. Our results showed that 100 µg/mL and 50 µg/mL of costunolide, and 50 µg/mL of parthenolide applied to the cellular disease model ameliorated the cytotoxicity caused by MPP+ exposure. We found that acetylcholinesterase activity assays exhibited that terpenoids could ameliorate and restore the enzyme activity as in negative control levels. The oxidative stress parameter analyses revealed that terpenoid application could enhance antioxidant levels and decrease oxidative stress in the cultures. In conclusion, we reported that these two terpenoid molecules could be used in the development of efficient treatment strategies for PD patients.

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Fazal, Karim, Gayan Perera, Mizanur Khondoker, Robert Howard, and Robert Stewart. "Associations of centrally acting ACE inhibitors with cognitive decline and survival in Alzheimer's disease." BJPsych Open 3, no. 4 (July 2017): 158–64. http://dx.doi.org/10.1192/bjpo.bp.116.004184.

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BackgroundCognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs).AimsTo compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither.MethodRoutine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis.ResultsIn the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival.ConclusionsIn people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression.

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Khalifa, Samah A., and Eda M. A. Alshailabi. "BIOCHEMICAL INVESTIGATIONSOF THE EFFECT OF XANAX ON THE CEREBELLAR TISSUES OF MALE MICE." EPH - International Journal of Applied Science 7, no. 4 (December 27, 2021): 16–20. http://dx.doi.org/10.53555/eijas.v7i4.42.

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Xanax is an agent with hypnogenic, anxiolytic, anticonvulsant, and muscle relaxant properties and has generally been used as a hypnotic/tranquilizer. The aim of this paper was to investigate the effect of Xanax on acetylcholinesterase and glutathionestransferase enzyme activities on the cerebellar tissues of male mice. Sixty male mice were randomly assigned into four groups (15 mice/each) according to their approximately equal mean body weight. Mice that received orally by gavage 0.5 ml saline solution of 0.9% NaCl were considered as a control mice. Other experimental mice were daily administered orally by gavage with 0.5 ml of different three doses of Xanax (0.5, 1 and 1.5 mg/kg bw), for two months. Biochemical analyses revealed significant decreases in the activities of acetylcholinesterase and glutathionestransferase enzyme in the brain tissues of mice administered with the three doses of Xanax. The major mechanism involved appears to be the result of oxidative stress scavenging action on the neuronal cells of cerebellar cortex of male mice.

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Nascimento, Giovana Coutinho Zulin, Carla Letícia Gediel Rivero-Wendt, Ana Luisa Miranda-Vilela, Doroty Mesquita Dourado, Gilberto Gonçalves Facco, Vania Cláudia Olivon, Karla Rejane de Andrade Porto, et al. "Acetylcholinesterase inhibitory potential and lack of toxicity of Psychotria carthagenensis infusions." Research, Society and Development 10, no. 4 (April 8, 2021): e22810414059. http://dx.doi.org/10.33448/rsd-v10i4.14059.

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Анотація:

We aimed to evaluate the phytochemical composition of the aqueous extract of leaves of Psychotria carthagenensis, and its possible toxicological effects at 200 µg/Kg on Rattus norvegicus. The aqueous extract was used for preliminary phytochemical analyses using standard procedures. After, male albino Wistar rats (N= 6/group) received by gavage for 15 consecutive days, infusions with fresh (FL) and dry leaf (DL) at 200 µg/kg; controls received filtered water (negative) or clonazepam solution at 0.5 mg/kg (positive). Hematological analyses, determination of serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, uric acid, total plasma protein (TPP), quantification of serum cholinesterase (AChE), and histological analyses of kidneys and liver were carried out. By the phytochemical analysis of the aqueous leaf extract, it was possible to detect the total phenols, flavonoids, tannins and alkaloids, the latter having been recorded for the species for the first time in this study. ALT and AST levels indicated an increase in these plasma enzymes, but histological analysis of kidneys and liver showed only slight changes. Inhibition of AChE levels was related mainly to alkaloids. The infusion showed the pharmacological potential of the plant as an alternative in the treatment of neurodegenerative diseases.

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Cardozo, Mario G., Takatoshi Kawai, Youichi Iimura, Hachiro Sugimoto, Yoshiharu Yamanishi, and A. J. Hopfinger. "Conformational analyses and molecular-shape comparisons of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase." Journal of Medicinal Chemistry 35, no. 3 (February 1992): 590–601. http://dx.doi.org/10.1021/jm00081a023.

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Cheng, Yuhui, Xiaolin Cheng, Zoran Radić, and J. Andrew McCammon. "Acetylcholinesterase: Mechanisms of Covalent Inhibition of Wild-Type and H447I Mutant Determined by Computational Analyses." Journal of the American Chemical Society 129, no. 20 (May 2007): 6562–70. http://dx.doi.org/10.1021/ja070601r.

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Bonesi, Marco, Maria Tenuta, Monica Loizzo, Vincenzo Sicari, and Rosa Tundis. "Potential Application of Prunus armeniaca L. and P. domestica L. Leaf Essential Oils as Antioxidant and of Cholinesterases Inhibitors." Antioxidants 8, no. 1 (December 21, 2018): 2. http://dx.doi.org/10.3390/antiox8010002.

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Анотація:

The aim of this work is to investigate the in vitro acetylcholinesterase (AChE) and butyrycholinesterase (BChE) inhibitory activities of essential oils obtained by hydrodistillation from the leaves of Prunus armeniaca and P. domestica in relation to their composition, analysed by Gas Chromatography–Flame Ionization Detector (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS) analyses, at different times. Moreover, considering the role of free radicals in the progression of neurodegenerative disorders, the antioxidant properties of essential oils were investigated by using, 2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and β-carotene bleaching tests. The relative antioxidant capacity index (RACI) was used to achieve more comprehensive comparison between analysed antioxidant effects of essential oils. P. armeniaca oils were more active than P. domestica oils against AChE. Against BChE, the most active was the essential oil from P. domestica leaves collected in August with an IC50 value of 95.80 μg/mL. This oil exerted the highest inhibitory activity of lipid peroxidation with IC50 values of 11.15 and 11.39 μg/mL after 30 and 60 min of incubation, respectively. All samples demonstrated a remarkable ABTS radicals scavenging activity, with IC50 values in the range 0.45–0.57 μg/mL in comparison to the positive control, ascorbic acid.

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Sverdrup Efjestad, Anne, Hege Ihle-Hansen, Vidar Hjellvik, and Hege Salvesen Blix. "Comedication and Treatment Length in Users of Acetylcholinesterase Inhibitors." Dementia and Geriatric Cognitive Disorders Extra 7, no. 1 (February 9, 2017): 30–40. http://dx.doi.org/10.1159/000454948.

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Анотація:

Background/Aims: Reduced clinical effect on cognitive decline in dementia by acetylcholinesterase inhibitors (AChEIs) may be due to concurrent use of drugs with anticholinergic properties. The aim was to analyze the incidence of AChEI use and comedication with drugs with anticholinergic properties and other potential unfavorable effects. Methods: A prospective study applying drug use data from the Norwegian Prescription Database. Anticholinergic Drug Scale (ADS) scores were used as a measure of overall anticholinergic burden. Results: Patients with high ADS scores were more frequently discontinuing treatment early. Coprescribing of antipsychotics was strongly associated with early discontinuation of AChEI treatment. Conclusion: Coprescribing with potentially unfavorable medications was common. A high ADS score was associated with early discontinuation of treatment.

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Turkiewicz, Igor, Aneta Wojdyło, Karolina Tkacz, Paulina Nowicka, and Francisca Hernández. "Antidiabetic, Anticholinesterase and Antioxidant Activity vs. Terpenoids and Phenolic Compounds in Selected New Cultivars and Hybrids of Artichoke Cynara scolymus L." Molecules 24, no. 7 (March 28, 2019): 1222. http://dx.doi.org/10.3390/molecules24071222.

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Анотація:

The aim of the study was to analyze the chemical composition of new artichoke cultivars and hybrids and to assess their potential health-promoting properties. Polyphenols, carotenoids and chlorophylls were identified by liquid chromatography-photodiode detector-mass spectrometry/quadrupole time of flight (LC-PDA-MS/QTof) and quantified by ultra performance liquid chromatography-photodiode detector (UPLC-PDA). Sugar and organic acid profiles were prepared, and antioxidant capacity (ABTS, FRAP and ORAC) and in vitro antidiabetic (inhibition of α-amylase and α-glucosidase) and anticholinesterase (inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) potentials were evaluated. The analyses revealed a highly varied content of bioactive compounds and great health-promoting potential significantly depending on a cultivar. The content of polyphenolic compounds ranged from 1681.49 (“Sambo”) to 3638.91 (“Symphony”) mg/100 g of dry weight (DW). “Blanca de Tudela” contained the highest amounts of carotenoids and chlorophylls (3761.91 mg/100 g DW) and exhibited high ABTS and ORAC capacity. Inhibition of antidiabetic enzymes was significant in cvs. “Symphony” and “Calico”. Additionally, all tested cultivars and hybrids turned out to be effective inhibitors of neurodegenerative enzymes.

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Akinlolu, Adelaja, Mubarak Ameen, Tobilola Quadri, Kayode Odubela, Gabriel Omotoso, Rahmat Yahya, Sikiru Biliaminu, Muinat Adeyanju, Gabriel Ebito, and Jubril Otulana. "Extraction, isolation and evaluation of anti-toxic principles from Moringa oleifera (MOF6) and Myristica fragrans (Trimyristin) upregulated Acetylcholinesterase concentrations in Sodium arsenite-induced neurotoxicity in rats." Journal of Phytomedicine and Therapeutics 19, no. 2 (March 11, 2021): 466–82. http://dx.doi.org/10.4314/jopat.v19i2.1.

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This study evaluated the neuroprotective effects of MOF6 (isolated from Moringa oleifera leaves) and Trimyristin (isolated from Myristica fragrans seeds) on Acetylcholinesterase concentrations in cerebral cortices of rats with Sodium arsenite-induced neurotoxicity. Sixty-five adult male rats (150 g-250 g) were randomly divided into thirteen groups comprising of five rats per group. Groups 1 and 3 received physiological saline and 1 ml/200 g bodyweight of Olive oil respectively for 9 weeks. Group 2 received 20 mg/kg bodyweight of Sodium arsenite (SA) for 6 weeks and left untreated for another 3 weeks. Groups 4-5 received 20 mg/kg bodyweight of SA for 3 weeks followed by treatments with 5.0 and 7.5 mg/kg bodyweight of MOF6 respectively for 6 weeks. Groups 6-7 received 20 mg/kg bodyweight of SA for 3 weeks followed by treatments with 15 and 30 mg/kg bodyweight of Trimyristin respectively for 6 weeks. Groups 8-11 received 5.0 and 7.5 mg/kg bodyweight of MOF6; 15 and 30 mg/kg bodyweight of Trimyristin respectively for 9 weeks. Groups 12-13 received 7.5 mg/kg bodyweight of MOF6 and 30 mg/kg bodyweight of Trimyristin respectively for 6 weeks followed by co-administration of each extract dose with 20 mg/kg bodyweight of SA for another 3 weeks. Histological examination of cerebral cortices and biochemical analyses of Acetylcholinesterase concentrations were carried out in all rats. Computed data were analyzed using Microsoft Excel 2016 with statistical significance at p≤0.05. Histo-pathological evaluations revealed normal histo-architecture of cerebral cortices of all rats. Results showed statistically significant (p≤0.05) increases in Acetylcholinesterase concentrations in rats of Groups 1-10 and 12 compared with Group 2 (2.78±1.76 𝜇mole/min/g). 7.5 mg/kg bodyweight of MOF6 showed the best therapeutic and neuro-regenerative potential against SA-induced neurotoxicity.Conclusions: Our findings implied that MOF6 and Trimyristin reversed downregulation of Acetylcholinesterase concentrations in SA-induced neurotoxicity in rats; and possess neuro-protective and neuro-regenerative potentials.

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Sarikaya, Buket Bozkurt, Nehir Unver Somer, Gulen Irem Kaya, Mustafa Ali Onur, Jaume Bastida, and Strahil Berkov. "GC-MS Investigation and Acetylcholinesterase Inhibitory Activity of Galanthus rizehensis." Zeitschrift für Naturforschung C 68, no. 3-4 (April 1, 2013): 118–24. http://dx.doi.org/10.1515/znc-2013-3-407.

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GC-MS (gas chromatography-mass spectrometry) analyses of alkaloids in the aerial parts and bulbs of Galanthus rizehensis Stern (Amaryllidaceae), collected during two different vegetation periods, was performed. Twenty three alkaloids were identified in four different alkaloid extracts. Acetylcholinesterase (AChE) inhibitory activities of the alkaloid extracts were tested. Both the highest alkaloid diversity and the most potent inhibitory activity (IC50 12.94 μg/ml) were obtained in extracts from the bulbs of G. rizehensis collected during the fruiting period.

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Doan, Nguyet Thi, Duong Hoang Nguyen, and Tru Van Nguyen. "Neuroprotective Activity of Catharanthus roseus Ethanol Extract by Acetylcholinesterase Inhibition and Neurite Outgrowth Studies." Annual Research & Review in Biology 38, no. 8 (October 30, 2023): 1–12. http://dx.doi.org/10.9734/arrb/2023/v38i830598.

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Aims: To investigate biological activities for neuroprotective effect of Catharanthus roseus. Methodology: Catharanthus roseus was identified using DNA barcoding, utilizing matK, trnH-psbA, and rbcL markers. Additionally, thin-layer chromatography (TLC) method was used to analyze the phytochemistry compounds present in the C. roseus extracts. Moreover, acetylcholinesterase (AChE) inhibition activity was tested using a modified Ellman’s method. Finally, neurite outgrowth activity was determined in rat glial C6 cells treated with varying concentrations of C. roseus extracts. Results: Overall, the plant samples which were collected in Laocai, Vietnam were successfully identified through DNA barcoding regions, using trnH-psbA, matK, and rbcL genes. Phytochemical analysis detected the presence of sterols, terpenoids, flavonoids, polyphenolic in the ethanol extract and its fraction from C. roseus. Additionally, the extracts of C. roseus displayed remarkably high acetylcholinesterase inhibitory activity. Moreover, the ethanol extract of C. roseus shown the most potent neurotrophic activity in a preliminary cell-based screening based on C6 cells neurite outgrowth. Conclusion: These results demonstrate that Catharanthus roseus could be a strong candidate for developing pharmacological drugs to treat neurodegenerative diseases.

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46

Theroux, Mary C., Robert E. Akins, Carol Barone, Bobbie Boyce, Freeman Miller, and Kirk W. Dabney. "Neuromuscular Junctions in Cerebral Palsy." Anesthesiology 96, no. 2 (February 1, 2002): 330–35. http://dx.doi.org/10.1097/00000542-200202000-00017.

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Background Cerebral palsy (CP) is the most prevalent neurologic disease in children. A primary deficit in CP is neuromuscular dysfunction; however, neuromuscular junctions in children with CP have not been studied. Evidence exists that up-regulation of acetylcholine receptors (AChRs) may be present in children with CP, and the current study was undertaken to examine this possibility. Methods Thirty-nine children with spastic CP and 25 neurologically normal children were enrolled in the study. Paraspinal muscles underwent biopsy during scheduled spinal fusion surgery. Two sets of assessments were performed on the biopsy specimens: (1) reverse-transcription polymerase chain reaction and Western blotting to evaluate the expression of the gamma subunit of the AChR; and (2) histologic evaluation using a double-stain technique for AChR and acetylcholinesterase, wherein acetylcholinesterase staining defined the limits of the neuromuscular junction, and AChR staining that appeared outside of these limits indicated an abnormal distribution of AChRs. Results Reverse-transcription polymerase chain reaction and Western blot analyses showed that neither the CP nor non-CP samples had detectable gamma-AChR subunit. Histologic analysis indicated that 11 of 39 children with CP and none of 20 children with idiopathic scoliosis scored positive for the presence of AChR outside of the neuromuscular junction (P = 0.0085). Conclusion A subset of children with CP have an abnormal distribution of AChR relative to the acetylcholinesterase found at the neuromuscular junction. The altered distribution of AChR in CP was not associated with a detectable presence of the gamma-AChR subunit, suggesting that the nonjunctional AChRs in CP does not contain the gamma subunit.

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Arman, Sezgi, and Sema İşisağ Üçüncü. "Impact of acute fonofos exposure on skeletal muscle of zebrafish: Histopathological and biometric analyses." Annales de Limnologie - International Journal of Limnology 57 (2021): 25. http://dx.doi.org/10.1051/limn/2021023.

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It is widely known that pesticides generally do not show target specificity, and off-target species are strikingly affected by these chemicals. In the current work, histological changes in skeletal muscles of zebrafish (Danio rerio) caused by fonofos, an acetylcholinesterase (AChE) inhibitor organophosphate insecticide, were examined. Zebrafish were treated with 1 mg/L, 2 mg/L and 4 mg/L of fonofos for 96 hours. Skeletal muscle samples were removed from the pectoral region and embedded in paraffin. Sections were stained with Mayer's Hematoxylin and Eosin, Gomori's Trichrome and Periodic Acid Schiff techniques. Histopathological alterations were investigated by light microscopy. Fibrosis, intramyofibrillar vacuoles, disintegrated myofibrils, splitting of myofibers, atrophic and disappeared fibers, histoarchitectural loss, necrosis and progressive decrement in glycogen content were noted. Muscle fiber diameter measurements were also performed. Statistical analysis showed that measured fiber diameters of all fonofos exposed groups were significantly different from the control group, and they decreased in a concentration-dependent manner. These results suggested that fonofos caused significant myoarchitectural impairments in non-target freshwater zebrafish.

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Kaur, Ishtdeep, Nancy Suthar, Jasmeen Kaur, Yogita Bansal, and Gulshan Bansal. "Accelerated Stability Studies on Dried Extracts of Centella asiatica Through Chemical, HPLC, HPTLC, and Biological Activity Analyses." Journal of Evidence-Based Complementary & Alternative Medicine 21, no. 4 (August 6, 2016): NP127—NP137. http://dx.doi.org/10.1177/2156587216661468.

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Regulatory guidelines recommend systematic stability studies on a herbal product to establish its shelf life. In the present study, commercial extracts (Types I and II) and freshly prepared extract (Type III) of Centella asiatica were subjected to accelerated stability testing for 6 months. Control and stability samples were evaluated for organoleptics, pH, moisture, total phenolic content (TPC), asiatic acid, kaempherol, and high-performance thin layer chromatography fingerprints, and for antioxidant and acetylcholinesterase inhibitory activities. Markers and TPC and both the activities of each extract decreased in stability samples with respect to control. These losses were maximum in Type I extract and minimum in Type III extract. Higher stability of Type III extract than others might be attributed to the additional phytoconstituents and/or preservatives in it. Pearson correlation analysis of the results suggested that TPC, asiatic acid, and kaempferol can be taken as chemical markers to assess chemical and therapeutic shelf lives of herbal products containing Centella asiatica.

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AlSuhaibani, E., C. C. Voudouris, R. Al-Atiyat, A. Kotzamumin, J. Vontas, and J. T. Margaritopoulos. "Identification of a point mutation in the ace1 gene of Therioaphis trifolli maculata and detection of insecticide resistance by a diagnostic PCR–RFLP assay." Bulletin of Entomological Research 105, no. 6 (August 17, 2015): 712–16. http://dx.doi.org/10.1017/s0007485315000668.

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AbstractAphids are important agricultural pests worldwide. Their control is largely based on chemical insecticides. One species that shows important invasive abilities and host-plant-related differences is Therioaphis trifolii (Monell) (Hemiptera: Aphididae). T. trifolii maculata, also known as spotted alfalfa aphid (SAA), can be very injurious to alfalfa crops in certain regions, such as in Saudi Arabia for effective control it is essential to diagnose and monitor the resistance mechanisms in the SAA populations. In the present study, we analysed acetylcholinesterase (ace) target site insensitivity mechanisms. A 650 bp length DNA containing the putative acetylcholinesterase (ace1) precursor was obtained and compared with other Hemipteran species. The sequences of many individual aphids collected from alfalfa crops in Saudi Arabia were analysed for the presence of resistance mutations: no resistance mutations were found at the resistance mutation loci 302; however, the presence of a serine–phenylalanine substitution (S431F) was identified in one individual. The S431F substitution, has been shown to confer significant levels of both organophosphate and carbamate resistance in other aphid species, and is now found for the first time in T. trifolii. We subsequently developed a simple polymerase chain reaction–restriction fragment length polymorphism assays for the S431F mutation, using a TaqI restriction site destroyed by the S431F mutation. The novel diagnostic assay may support the implementation of Insecticide Resistance Management strategies, for the control of SAA in alfalfa crops in the Kingdom of Saudi Arabia, and other countries worldwide.

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Arsic, Biljana, Stefan Petrovic, Jelena Mrmosanin, Ivana Dimitrijevic, Snezana Tosic, Gordana Stojanovic, Sanja Glisic, and Jelena Milicevic. "Stability and computational analyses of selected pesticides in use in the Republic of Serbia." Journal of the Serbian Chemical Society, no. 00 (2023): 102. http://dx.doi.org/10.2298/jsc230714102a.

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Pesticides commonly used in the Republic of Serbia (tebuconazole, pendimethalin, pyraclostrobin, propiconazole, and famoxadone) have high stability, so their potential toxicity to humans needs to be investigated. These pesticides are in use in the Republic of Serbia in various formulations. Their toxicity and interactions with acetylcholinesterase were thoroughly investigated in this study using computational tools. The ADMET (Adsorption, Distribution, Metabolism, Excretion, Toxicity) study showed that all of them are good oral compounds, and that pendimethalin was a mutagenic compound. Glide scores ranged from -18.41 kJ mol-1 (pendimethalin) to -27.61 kJ mol-1 (famoxadone) in Mus musculus, and from -19.58 kJ mol-1 (pendimethalin) to -24.31 kJ mol-1 (propiconazole) in Homo sapiens. In addition, the experimental stability of the pesticides solutions in methanol was studied using the fast GC-MS (retention times of the studied pesticides ranged from 14.47 min (pendimethalin) to 22 min (famoxadone)). They showed good stability over time, apart from pyraclostrobin which decomposed mainly into its des-methoxy derivative after 20 months. Based on the promising modeling results, pyraclostrobin and famoxadone emerge as potential candidates for further investigation in the treatment of Alzheimer's disease, taking care to increase their stability.

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