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Piper baccatum is a woody climber and grows throughout the tropics mostly in Southeast Asia such as Thailand, Malaysia, Singapore, and Indonesia. The studies on essential oil composition and anticholinesterase activities were performed, along with molecular docking of all components. The essential oil was obtained by hydrodistillation and analyzed by GC-FID and GC-MS, while anticholinesterase activity was assessed using Ellman method. A total of 14 components were identified, representing 98.1% of the total composition of the essential oil. The major identified components were β-caryophyllene (30.7%), camphene (22.1%), eucalyptol (14.9%), γ-muurolene (6.9%), and α-pinene (5.3%). A moderate inhibitory effect was observed for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 80.5 and 96.4 μg/mL, respectively. Molecular docking studies of P. baccatum components with AChE and BChE revealed binding energy ranges of -5.6 to -8.5 Kcal/mol and -5.2 to -7.8 Kcal/mol, respectively, predominantly involving hydrophobic interactions with active site residues. Notably, β-caryophyllene and γ-muurolene exhibited superior binding energy profiles with both AChE and BChE compared to other components. The docking results underscore the potential of P. baccatum essential oil components as cholinesterase inhibitors, with implications for applications in food, aromatherapy, and pharmaceutical industries. The identified components, particularly β-caryophyllene and γ-muurolene, showcase promising attributes for further exploration in developing therapeutic interventions targeting cholinesterase-related conditions. This essential oil in general could be potentially used as a cholinesterase inhibitor with possible applications in food, aromatherapy, and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

GC/MS analysis of Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq. leaves revealed the identification of 73 components, with an evident greater contribution of monoterpenes hydrocarbons to their total volatiles. α-Pinene (37.5%) and β-caryophyllene (27.4%) were the most abundant compounds in M. koenigii leaves and β-phellandrene (40.7%) in M. paniculata leaves, using headspace. β-Phellandrene (33.7%) was the major constituent by M. koenigii leaves where germacrene D (23.8%), and δ-elemene (22.0%) were predominant in M. paniculata leaves, using steam distillation. M. koenigii leaves oil showed quite remarkable cholinesterase inhibitory activity, where oil of M. paniculata leaves showed strong inhibitory activity against AChE (IC50=13.2 ± 0.9 µg/mL) and BChE (IC50=5.1 ± 0.3 µg/mL). Germacrene D, α-zingiberene, and δ-elemene showed higher affinity to BChE than AChE as revealed from docking scores (S = −5.65 to −6.03 Kcal/mol) for BChE and (S = −5.56 to −6.25 Kcal/mol) for AChE. [ABSTRACT FROM AUTHOR]

Cholinesterase inhibitors, along with memantine, are the mainstay of symptomatic treatment for AD (Alzheimer's disease); however, these medications are typically administered orally, which can be difficult for people with AD and their caregivers. In this drug profile and narrative review, the authors trace the development of the new FDA-approved transdermal donepezil. The authors discuss the studies showing its bioequivalence with the oral formulation, including two double-blinded placebo controlled non-inferiority trials. The authors also compare the patch to the only other transdermal cholinesterase inhibitor on the market, rivastigmine, and highlight the potential advantages and disadvantages between these two treatments. While the patch is bio-equivalent, it is rather large and may not be affordable for some patients. In addition, there is no high dose (e.g. 23 mg) equivalent. Nevertheless, transdermal donepezil will be useful for people with AD and their caregivers, given its effectiveness and potential convenience. [ABSTRACT FROM AUTHOR]

The EtOH extracts of the leaves of two new cultivars (Uysal-SFU and Turgut-SFT) of Salvia fruticosa Mill. was tested against acetylcholinesterase (IC50: 30.62 ± 3.27 and 32.97 ± 2.33 µg/mL for SFU and SFT, respectively) and butyrylcholinesterase (IC50: 69.91 ± 1.08 µg/mL and 86.55 ± 1.26 µg/mL), respectively, relevant to Alzheimer's disease. The essential oils showed a stumpy inhibition against AChE and no inhibition against BChE. DPPH radical scavenging activity of the extracts (86.70 ± 0.17% and 86.14 ± 1.13% for SFU and SFT, respectively) was stronger than that of quercetin (85.51 ± 0.17%): Their (1.24 ± 0.05 and 1.04 ± 0.16 for SFU and SFT, respectively) ferric-reducing antioxidant power were close to that of the reference (e.g. quercetin, 1.42 ± 0.14). Molecular docking simulations were performed on their major monoterpenes. Our findings revealed that the leaf EtOH extracts of two cultivars are promising inhibitors of both AChE and BChE. [ABSTRACT FROM AUTHOR]

A series of OA-tacrine hybrids with the alkylamine linker was designed, synthesized, and evaluated as effective cholinesterase inhibitors for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some hybrids possessed significant inhibitory activities against acetylcholinesterase (AChE). Among them, compounds B4 (hAChE, IC50 = 14.37 ± 1.89 nM; SI > 695.89) and D4 (hAChE, IC50 = 0.18 ± 0.01 nM; SI = 3374.44) showed excellent inhibitory activities and selectivity for AChE as well as low nerve cell toxicity. Furthermore, compounds B4 and D4 exhibited lower hepatotoxicity than tacrine in cell viability, apoptosis, and intracellular ROS production for HepG2 cells. These properties of compounds B4 and D4 suggest that they deserve further investigation as promising agents for the prospective treatment of AD. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Alzheimer's disease (AD) are multifactorial with several different pathologic mechanisms. Therefore, it is assumed that multitargeted-directed ligands (MTDLs) which interact with different biological targets relevant to the diseases, might offer an improved therapeutic alternative than using the traditional "one-target, one-molecule" approach. Herein, we describe new benzothiazole-based derivatives as a privileged scaffold for histamine H3 receptor ligands (H3R). The most affine compound, the 3-(azepan-1-yl)propyloxy-linked benzothiazole derivative 4b, displayed a Ki value of 0.012 μM. The multitargeting potential of these H3R ligands towards AChE, BuChE and MAO-B enzymes was evaluated to yield compound 3s (pyrrolidin-1-yl-(6-((5-(pyrrolidin-1-yl)pentyl)oxy)benzo[d]thiazol-2-yl)methanone) as the most promising MTDL with a Ki value of 0.036 μM at H3R and IC50 values of 6.7 µM, 2.35 µM, and 1.6 µM towards AChE, BuChE, and MAO-B, respectively. These findings suggest that compound 3s can be a lead structure for developing new multi-targeting anti-AD agents. [ABSTRACT FROM AUTHOR]

A new terrein dimer named lichtheicol A (1) and a new meroterpene named lichtheiterpene A (2), were isolated from the mangrove endophytic fungus Lichtheimia sp. J2B1, together with 10 known compounds (3–12). The planar structures and absolute configurations of 1 and 2 were established by a combination of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 exhibited marked inhibitory effects against butyrylcholinesterase (BuChE) with IC50 values of 0.71 and 0.53 μM, respectively. [ABSTRACT FROM AUTHOR]

A series of arylated huperzine A (HPA) derivatives (1–24) were efficiently synthesized in good yields (45–88% yields) through the late-stage modification of structurally complex natural anti-Alzheimer's disease (AD) drug huperzine A (HPA), using the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. The acetylcholinesterase (AChE) inhibitory activity of all synthesized compounds was evaluated to screen the potential anti-AD bioactive molecules. The results showed that introducing the aryl groups to C-1 position of HPA resulted in the unsatisfactory AChE inhibitory activity. The present study demonstrably verifies pyridone carbonyl group could be the necessary and unchangeable pharmacophore for maintaining HPA's anti-AChE potency, and provides the helpful information on the further research for developing anti-AD HPA analogues. [ABSTRACT FROM AUTHOR]

Five selected medicinal plants in the family Zingiberaceae, Alpinia nigra, Boesenbergia maxwellii, Etlingera araneosa, Meistera koenigii, and Wurfbainia biflora, were collected from Thailand. HPLC was used to determine the content of phenolic compounds in their ethanolic extracts. The total phenolic contents and the total flavonoid contents of M. koenigii were found to be higher than that of the others. The antioxidant activity of the extracts was assayed by two methods, namely ABTS and DPPH assays using HPTLC and a microplate spectrophotometer. Anticholinesterase activity was screened by the Ellman method against acetylcholinesterase, the chief enzyme of Alzheimer's disease. The results showed mild acetylcholinesterase effects. The results indicated that these five ginger species, especially M. koenigii have the potential to be a good source of natural antioxidants and anticholinesterase agents that could be further applied in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders among the older population. Sleep disruption and circadian rhythm disorders often develop in AD patients, and many experience sleeping difficulties requiring pharmacological and non-pharmacological interventions. This review appraised the evidence from clinical studies on various pharmacological and non-pharmacological therapies for sleep disturbances in AD patients and proposed an algorithm to manage sleep disturbances in this population of patients. Non-pharmacological interventions are generally preferred as the first-line approach to improve sleep-related symptoms in AD due to their favorable safety profile. However, when non-pharmacological interventions alone are insufficient, a range of pharmacological agents can be considered. Trazodone and melatonin are commonly used as adjunctive therapies, while Z-drugs including zopiclone and zolpidem are specifically employed to treat insomnia in patients with late-onset AD. Furthermore, a newer class of agents known as dual orexin receptor antagonists has emerged and gained approval for improving sleep onset and maintenance in AD patients. [ABSTRACT FROM AUTHOR]

Cholinesterase (ChE) is a kind of important enzyme in a range of significant areas such as toxicology, pharmacology, and neurobiology. ChE, which can be irreversibly inhibited with organophosphorus agents (OPs), plays an important role in cholinergic syndrome. Recently, many efforts have been devoted to developing ChE sensor. Spectroscopic methods, including fluorescence, colorimetric and UV-vis, chemiluminescence (CL), and surface enhanced Raman scattering (SERS) are the most widely used techniques for the ChE activity detection. In these developed spectroscopic techniques, biosensors using nanomaterials or probe or chromogenic agent are highly promising because of the enhanced sensitivity, fast response time, wide detection range and system miniaturization. This paper reviews the development, application, and research trend of spectroscopic methods of ChE activity and its inhibitors in the last decade. Furthermore, the prospects for ChE detection are also discussed. [ABSTRACT FROM AUTHOR]

Pesticide poisonings, intentional as well as accidental, are common, especially in undeveloped and developing countries. The goal of this study was to analyze the clinical presentation of patients hospitalized due to acute organophosphate (OPP) or carbamate pesticide (CP) poisoning as well as to analyze the factors that potentially influenced the severity and outcome of the poisonings. A retrospective cross-sectional study was performed. The age and gender of each patient were recorded, the type of ingested pesticide, whether the poisoning was intentional or accidental, number of days of hospitalization, the severity of the poisoning, and the outcome of the treatment (i.e., whether the patient survived or not). Clinical aspects of poisonings were analyzed, as well as the therapeutic measures performed. 60 patients were hospitalized due to acute OPP or CP poisoning, out of 51 (85.00%) were cases of intentional self-poisoning. The majority of patients were poisoned by OPPs (76.67%), in one-third the causative agent was malathion, followed in frequency by chlorpyrifos and diazinon. Dimethoate poisonings were manifested with the most severe clinical picture. A 70% or lower activity of reference values of acetylcholinesterase and butyrylcholinesterase was found in 50% and 58% of patients, respectively. The most common symptom was miosis (58.33%), followed by nausea and vomiting. Pralidoxime reactivated acetylcholinesterase inhibited by chlorpyrifos or diazinon, but not with malathion or dimethoate. Impairment of consciousness and respiratory failure, as well as the degree of acetylcholinesterase and butyrylcholinesterase inhibition, were prognostic signs of the severity of poisoning. The lethal outcome was more often found in older patients (t = 2.41, p = 0.019). The type of ingested pesticide significantly affects the severity and outcome of poisoning as well as the effectiveness of antidotes. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase inhibitors (AChEIs) are used off-label, in both adult and pediatric patients, to help further neuro-recovery after traumatic brain injury (TBI). Evidence is limited and piecemeal. This review describes how TBI affects the cholinergic system and consolidates evidence supporting or refuting the use of AChEIs following TBI. NCBI MEDLINE search included all articles published through March 2021 on AChEI use in acute and post-acute adult TBI rehabilitation (treatment began <90 days or ≥90 days since injury, respectively), and in pediatric TBI rehabilitation. Further, we checked ClinicalTrials.gov for ongoing trials using AChEIs for TBI rehabilitation in the United States. 27 original articles from NCBI Medline, published through March 2021, were included. The use of AChEIs following TBI in acute and post-acute rehabilitation settings, in both adult and pediatric patients, along with medication side effects, is discussed. Most studies showed benefits with only moderate effect sizes because of small sample sizes. Reported side effects are minimal and stop soon after AChEIs is discontinued. Conclusions are limited by paucity of research; but fortunately, a large randomized controlled trial is ongoing, and more are needed to truly determine the efficacy of AChEIs in helping with recovery from TBI. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and β-secretase inhibitory activity. The IC50 value of compound 20 against acetylcholinesterase inhibition (0.086 ± 0.01 µmol·L−1) is similar to donepezil (0.085 ± 0.01 µmol·L−1) and is better than baicalein (0.404 ± 0.04 µmol·L−1). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 ± 0.03 µmol·L−1). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD. [ABSTRACT FROM AUTHOR]

Multitarget directed ligands (MTDLs) are emerging as promising treatment options for Alzheimer's disease (AD). Coumarin derivatives serve as a good starting point for designing MTDLs due to their inherent inhibition of monoamine oxidase (MAO) and cholinesterase enzymes, which are complicit in AD's complex pathophysiology. A preliminary series of 3,7-substituted coumarin derivatives were synthesised and evaluated for enzyme inhibitory activity, cytotoxicity as well as neuroprotective ability. The results indicated that the compounds are weak cholinesterase inhibitors with five compounds demonstrating relatively potent inhibition and selectivity towards MAO-B with IC50 values between 0.014 and 0.498 hx00B5;µM. Significant neuroprotective effects towards MPP+-compromised SH-SY5Y neuroblastoma cells were also observed, with no inherent cytotoxicity at 10 µM for all compounds. The overall results demonstrated that substitution of the phenylethyloxy moiety at the 7-position imparted superior general activity to the derivatives, with the propargylamine substitution at the 3-position, in particular, displaying the best MAO-B selectivity and neuroprotection. [ABSTRACT FROM AUTHOR]

We have designed unprecedented cholinesterase inhibitors based on 1-deoxynojirimycin as potential anti-Alzheimer's agents. Compounds are comprised of three key structural motifs: the iminosugar, for interaction with cholinesterase catalytic anionic site (CAS); a hydrocarbon tether with variable lengths, and a fragment derived from 2-phenylethanol for promoting interactions with peripheral anionic site (PAS). Title compounds exhibited good selectivity towards BuChE, strongly depending on the substitution pattern and the length of the tether. The lead compounds were found to be strong mixed inhibitors of BuChE (IC50 = 1.8 and 1.9 µM). The presumptive binding mode of the lead compound was analysed using molecular docking simulations, revealing H-bond interactions with the catalytic subsite (His438) and CAS (Trp82 and Glu197) and van der Waals interactions with PAS (Thr284, Pro285, Asn289). They also lacked significant antiproliferative activity against tumour and non-tumour cells at 100 µM, making them promising new agents for tackling Alzheimer's disease through the cholinergic approach. [ABSTRACT FROM AUTHOR]

This work reports for the first time the in vitro anti-oxidant (towards DPPH, ABTS, copper and iron), enzymatic inhibitory (on AChE, BuChE, α-glucosidase, α-amylase and tyrosinase), cytotoxicity (towards HepG2 and HEK 293 cells), and metabolomics (by HPLC-MS) of extracts from organs of Malcolmia littorea (L.) R.Br. Extracts were constituted mainly by phenolic acids and flavonoids, and main compounds were salicylic acid and luteolin-7-O-glucoside. Samples showed reduced radical scavenging and metal chelating capacity, and only the methanol extracts reduced iron. The root's ethanol and methanol extracts, and the aerial organ's ethanol extract exhibited the highest AChE inhibition. The root's ethanol extract displayed dual anti-cholinesterase activity. Samples showed a low capacity to inhibit α-amylase, but a high α-glucosidase inhibition was obtained with the root's and flower's ethanol extracts, and flower's methanol extract. Overall, samples displayed a high inhibition against tyrosinase, reduced HepG2 cellular viability and were less toxic towards HEK 293 cells. [ABSTRACT FROM AUTHOR]

Improvements and advances in health care over the past few decades have increased life expectancy and quality of life. However, this has resulted in an increase in non-communicable diseases like dementia, Alzheimer's Disease (AD), etc. AD most commonly affects the older population, but recent studies reveal that it can also affect people of any age group. As of now, there are no accessible treatments or therapies that reverse the progression of the disease. The few existing medications to treat AD include Donepezil (Aricept), Galantamine (Razadyne) and Rivastigmine (Exelon) provide only temporary relief and come with several side effects like diarrhoea, vomiting, nausea, fatigue, insomnia, loss of appetite, and weight loss. An effective and augmenting therapy with Cholinesterase inhibitors from natural products is gaining popularity among researchers. Plant sterols have been known to play roles in inhibiting proteins implicated in the development of AD. The present study highlights the significance and scope of Stigmasterol, a phytochemical in Saraca asoca in the alleviation of AD. Our study involving the use of QSAR, ADME, molecular interaction, and molecular docking has shown that Stigmasterol has the potential to be developed as a therapeutic drug to curb the progression of AD after thorough validation procedures. [ABSTRACT FROM AUTHOR]

Introduction: Our objective is to highlight the value of the neurophenomenological classification of complex visual hallucinations (VHs). This approach enabled the authors to successfully treat VHs of uncertain aetiology with cholinesterase inhibitors because the content of the hallucinations suggested dysfunction in cholinergic modulated networks. Methods: We utilise the single case report to describe the nature and content of chronic VHs experienced by a 49-year-old woman following a prolonged admission to ITU. Despite extensive investigation, no clear cause was identified for these hallucinations and the patient did not respond to rationalisation of medications or trials of antipsychotics. We therefore adopted the neurophenomenological approach to classifying and treating her VHs. Results: After several years of distressing visual hallucinations, a course of Rivastigmine was trialed despite no evidence suggestive of a Parkinsonian syndrome. Nevertheless, the patient reported a dose-effect response with significant reduction in the frequency and intensity of her hallucinations, almost to complete resolution. Conclusions: At present there is limited evidence about the medical management of visual hallucinations. This case report suggests that cholinesterase inhibitors may be of benefit, even in the absence of clear parkinsonsian features, if the form and content of the VHs suggest dysfunction in cholinergic modulated attentional networks. [ABSTRACT FROM AUTHOR]

The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors play a key role in treating Alzheimer's disease. This study proposes an approach that integrates a modified binary particle swarm optimization (PSO) with a machine learning algorithm for building QSAR models to predict the activity of inhibitors for AChE and BuChE enzymes. More precisely, it uses a transfer function to convert the continuous search space of PSO to binary. Furthermore, it utilizes the concepts of catfish effect and chaotic map to improve exploration ability in searching for an optimum subset of descriptors for QSAR model constructions. Then, through a statistical method, it employs a machine learning algorithm to evaluate the fitness value of each candidate subset of features. Different combinations of four transfer functions with four machine learning algorithms, including K-nearest neighbour, multiple linear regression, support vector machine, and regression tree, were used to build several variants of the proposed algorithm. QSAR models constructed by each version were verified by internal and external validations. The best variants were selected based on a method called sum of ranking differences. [ABSTRACT FROM AUTHOR]

Twelve novel 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives were synthesized via iodine-mediated oxidative cyclisation and confirmed by 1H NMR, 13C NMR and HRMS. The result of these derivatives' activities inhibiting acetylcholinesterase in vitro showed that 4 g and 4i had moderate inhibitory activities with 69.19% and 65.06%, respectively. The preliminary structure-activity relationships revealed that introduction of halogen atom on the para-position of phenyl of 7-diethylaminocoumarin-based 1,3,4-oxadiazole derivatives could enhance their activities. Molecular docking study suggested that 4 g possessed an optimal docking pose with interactions inside AChE. [ABSTRACT FROM AUTHOR]

Eugenia genus is known for its phenolic metabolites, which may influence the progression of the Alzheimer Disease. This study aimed to evaluate the anticholinesterase effects of six Eugenia species from Brazil. Leaves and stems were submitted to maceration (methanol) and partitioned with dichloromethane and ethyl acetate (EtOAc). Samples were screened (200 μg mL−1) for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). HPLC-ESI-MS/MS analysis allowed the identification of twenty-eight phenolic compounds. Regarding the enzymatic activity, EtOAc fraction of E. mattosii exhibited the best results. Chemical and pharmacological aspects of seasonal E. mattosii extracts were evaluated. The extract from leaves collected in the winter was the most effective for AChE, and the extract from leaves collected in the spring was the most effective for BuChE. Correlating the enzymatic results with the chemical data, it was possible to associate these effects to isoquercitrin, quercetin, catechin, epicatechin, procatecuic acid and myricitrin content. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase/Butyrylcholinesterase inhibitors are considered an effective method for treating Alzheimer's disease (AD). In this current work, we have computationally analyzed 11 new small molecule drugs used in various neurological diseases and Donepezil, a known inhibitor of acetylcholinesterase, as a positive control. We investigated these drugs for possible fundamental interactions with acetylcholinesterase and butyrylcholinesterase as both are critical in the pathophysiology of Alzheimer's disease. We have selected FDA approved compounds for repurposing as possible inhibitors of these enzymes and novel therapeutic option for Alzheimer's disease. We selected the top two molecules for each protein for their binding energies, interactions, and Donepezil, the most commonly used drug for AD treatment. Molecular simulation and dynamics studies of the top 2 drugs in each case and free energy analysis helped us reach further conclusions about the best possible drugs for repurposing. Brexipirazole and Deutetrabenazine produce encouraging results as butyrylcholinesterase and acetylcholinesterase inhibitors, respectively. [ABSTRACT FROM AUTHOR]

The neurocognitive benefits of donepezil are well recognised, but the potential side effects on cardiac conduction remain unclear. To investigate whether long-term donepezil therapy is associated with electrocardiographic (ECG) changes and in particular to assess its effects on the QT interval. We conducted a single centre retrospective analysis of patients admitted to our trust on donepezil therapy over a 12-month period. An admission resting 12-lead ECG was obtained and compared to their ECG prior to commencement of donepezil therapy to assess for any significant difference in ECG parameters. We identified 59 patients suitable for analysis. PR (177.0 ± 29.0 ms vs. 186.1 ± 34.2 ms, p = 0.04), QRS (101.7 ± 20.3 ms vs. 104.7 ± 22.3 ms, p = 0.04) and QT (393.3 ± 35.6 ms vs. 411.9 ± 44.6 ms, p = 0.002) interval prolongation were all associated with donepezil use. The increase in QT intervals remained significant on correction for heart rate; resulting in 8 (13.6%) patients developing high arrhythmogenic risk based on assessment using QT nomogram plots. Concomitant use of tricyclic antidepressants was associated with significant QT prolongation (QTcB: rpb = 0.344, p = 0.008, QTcFred: rpb = 0.382, p = 0.003, QTcFram: rpb = 0.379, p = 0.003, QTcH: rpb = 0.352, p = 0.006), while the use of rate-limiting calcium channel blockers was associated with significant PR prolongation (rpb = 0.314, p = 0.030), and beta-blockers with a reduction in heart rate (rpb = 0.256, p = 0.050). Our results clearly demonstrate that long-term use of donepezil is associated with prolongation of the QT interval. We suggest ECG evaluation should take place before and after donepezil initiation, and clinicians should be even more vigilant in those prescribed tricyclic antidepressants. [ABSTRACT FROM AUTHOR]

A new trace alkaloid possessing the lignan structure, named oleraisoindole A, was obtained from the extract of the Portulaca oleracea L.. The structure of oleraisoindole A was elucidated by 1D and 2D NMR and high resolution electrospray ionization time-of-flight mass spectroscopic methods. The compound presented an anticholinesterase effect with the IC50 value of 60.4 μM. [ABSTRACT FROM AUTHOR]

Effective therapy of Alzheimer's disease (AD) requires treatment with a combination of drugs that modulate various pathomechanisms contributing to the disease. In our research, we have focused on the development of multi-target-directed ligands – 5-HT6 receptor antagonists and cholinesterase inhibitors – with disease-modifying properties. We have performed extended in vitro (FRET assay) and in cellulo (Escherichia coli model of protein aggregation) studies on their β-secretase, tau, and amyloid β aggregation inhibitory activity. Within these multifunctional ligands, we have identified compound 17 with inhibitory potency against tau and amyloid β aggregation in in cellulo assay of 59% and 56% at 10 µM, respectively, hBACE IC50=4 µM, h5TH6 Ki=94 nM, hAChE IC50=26 nM, and eqBuChE IC50=5 nM. This study led to the development of multifunctional ligands with a broad range of biological activities crucial not only for the symptomatic but also for the disease-modifying treatment of AD. [ABSTRACT FROM AUTHOR]

There are numerous studies supporting the contribution of oxidative stress to the pathogenesis of epilepsy. Prolonged oxidative stress is associated with the overexpression of ATP-binding cassette transporters, which results in antiepileptic drugs resistance. During our studies, three 1,2,4-triazole-3-thione derivatives were evaluated for the antioxidant activity and anticonvulsant effect in the 6 Hz model of pharmacoresistant epilepsy. The investigated compounds exhibited 2-3 times more potent anticonvulsant activity than valproic acid in 6 Hz test in mice, which is well-established preclinical model of pharmacoresistant epilepsy. The antioxidant/ROS scavenging activity was confirmed in both single-electron transfer-based methods (DPPH and CUPRAC) and during flow cytometric analysis of total ROS activity in U-87 MG cells. Based on the enzymatic studies on human carbonic anhydrases (CAs), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), one can assume that the herein investigated drug candidates will not impair the cognitive processes mediated by CAs and will have minimal off-target cholinergic effects. [ABSTRACT FROM AUTHOR]

Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer's disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 ± 0.01 μM) is similar to the positive drug donepezil (0.059 ± 0.003 μM). According to the experimental results, Compounds 7, 13 show a certain effect in the in vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC50 in µM range) and AChE poorly (IC50≫100 µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors. Series of oxazole benzylamines were designed and synthesised The tested compounds showed binding selectivity for BChE Naphthoxazoles were more potent AChE inhibitors [ABSTRACT FROM AUTHOR]

Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer's disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 ± 0.11 µM; 15j, eqBChE IC50 = 0.16 ± 0.04 µM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD. [ABSTRACT FROM AUTHOR]

In vitro cholinesterase inhibition, antioxidant and anticancer potentials of the essential oils and extracts of flowers and aerial parts of Salvia verticillata subsp. amasiaca have been studied. The GC-MS and GC-FID analyses found that major components of the essential oils were caryophyllene oxide, caryophylladienol II, spathulenol, hexahydrofarnesyl acetone and phytol. Oxygenated sesquiterpenes and sesquiterpene hydrocarbons were identified in the essential oils as the dominating groups of compounds. Caryophyllene oxide indicated strong cholinesterase inhibitory activities and antioxidant effect. The essential oil from aerial parts exhibited high anticancer activity on U-87 MG and PC-3 cells with 0% and 45.56% cell viability, respectively. Microscopic analysis of different parts of the experimental plant revealed that glandular trichomes of flowers contain more oxygenated sesquiterpene hydrocarbons, while glandular trichomes of the aerial parts contain monoterpene hydrocarbons. It was confirmed that S. verticillata subsp. amasiaca had similar kinds of capitate and peltate trichomes like other Salvia members. [ABSTRACT FROM AUTHOR]

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). Acetylshikonin was the active principle component of Purple Gromwell that show anti-oxidative and anti-inflammatory effect. However, no data are available to elucidate the protective effect of acetylshikonin on COPD. Acetylshikonin could attenuate smoke-induced lung pathological changes, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) productions, and tissue damages caused by oxidative stress. Furthermore, acetylshikonin was found to enhance the expression of Nrf2 and Nur77-mediated COX-2 in vivo and in vitro. [ABSTRACT FROM AUTHOR]

This investigation displays antioxidant potential of Cymbocarpum erythraeum essential oils and their biological effects like cytotoxic and anticholinesterase. The antioxidant capacities of the essential oils were estimated by DPPH, TBA, TOS assays. The anticholinesterase activity of essential oils was estimated utilizing Ellman method. The human U-87MG and PC-3 were handled and measurements were estimated by MTT test. The root essential oil showed high cytotoxic activity on PC-3 cells with 48.33% whereas aerial part essential oils indicated high cytotoxic activity on U-87MG cells with 34.62% at 0.03 mg/L. Root oil presented the highest acetylcholinesterase and butyrylcholinesterase inhibition (IC50: 113, 197 µM, respectively). The GC-FID and GC-MS assays showed that major components of aerial part with flowers and root oils were (E)-2-decenal (52.1%); (E)-2-dodecenal (36.1%), and (E)-2-tetradecenal (22.3%), respectively. (E)-2-dodecenal was a major compound of root il and exhibited AChE and BuChE inhibitory (IC50: 100, 136 µM, respectively) and antioxidant effects. [ABSTRACT FROM AUTHOR]

α-mangostin, a polyphenol xanthone derivative, was mainly isolated from pericarps of the mangosteen fruit (Garcinia mangostana L.). In present investigation, a series of derivatives were designed, synthesised and evaluated in vitro for their inhibitory activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among the synthesised xanthones, compounds 1, 9, 13 and 16 showed AChE selective inhibitory activity, 15 was a BuChE selective inhibitor while 2, 3, 5, 6, 7, 12 and 14 were dual inhibitors. The most potent inhibitor of AChE was 16 while 5 was the most potent inhibitor of BuChE with IC50 values of 5.26 μM and 7.55 μM respectively. [ABSTRACT FROM AUTHOR]

Aim: The role of cognitive reserve (CR) in modulating dementia has been broadly investigated. We aimed to evaluate the long-term effects of CR on cognitive functions in outpatients newly treated with acetylcholinesterase inhibitors. Method: Fifty older adults with dementia (age 80 ± 6.4 years) were followed up over 27 months. CR was assessed with the Cognitive Reserve Index questionnaire (CRIq), which provides a Total CR index and three proxy measures: Education, Working Activity and Leisure Time. The association between CR and cognition, evaluated by the Mini-Mental State Examination (MMSE), was tested through linear mixed models. Results: The cognitive profile of High CR individuals (n = 16) was more fluctuating than that of patients with Low CR (n = 34) up to 15 months of treatment, showingan alternation of improvements and worsening. At linear mixed models, CRIq Total score was significantly associated with MMSE over the follow-up either when considered as continuous (β = 0.13 [95%CI:0.07–0.19], p <.001, per each 1-unit increase) orcategorical variable (β = 3.62 [95%CI:1.77–5.47], p =.002, High vs Low CR). Among the CR domains, higher CRIq Leisure-time scores were significantly associated with higher MMSE during the follow-up (β = 0.05 [95%CI:0.02–0.09], p =.009, per each 1-unit increase). Conclusion: The study indicates that higher CR, and especially Leisure Time-related CR, was associated with better cognitive performance in older outpatients with dementia treated with AChEI for 27 months. These findings suggest that Leisure Time-related CR could influence the evolution of dementia, and support the need of further investigations to verify the potential usefulness of interventions enhancing such domain even in advanced age. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the DNA damage in soybean growers during two agricultural periods of a crop season (high and low exposure) and a control group, as well as butyrylcholinesterase (BChE) activity during these exposure periods in order to estimate the degree of BChE inhibition for the exposed group. DNA damage in peripheral whole blood was evaluated by the comet assay and plasma BChE activity was accessed as a measure of exposure to cholinesterase inhibitors. None of the soybean growers reported using full Personal Protective Equipment (PPE). BChE was lower in high exposure period than in low exposure period and DNA damage index was significantly increased in the high exposure period than in the low exposure period. In addition, DNA damage in both exposure periods was higher than control group. No correlation was found between exposure time and DNA damage and BChE activity. However, negative correlation was observed between DNA damage in high and low exposure periods. The results indicate that soybean growers are exposed to cholinesterase inhibitors and to pesticides mixtures with genotoxic potential. [ABSTRACT FROM AUTHOR]

Introduction: Cortical cholinergic denervation resulting from degeneration of the nucleus basalis of Meynert (NBM) is a primary contributor to cognitive impairment and neuropsychiatric symptoms in the Lewy body diseases Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). Considering the morbidity associated with cognitive impairment and neuropsychiatric symptoms in these diseases, it is important to investigate all potential therapies to improve these symptoms. Areas covered: The authors review the current landscape of pharmacological and surgical therapies for mitigating the cortical cholinergic deficiency in PD, PDD, and DLB. Expert opinion: The cholinesterase inhibitors rivastigmine, donepezil, and galantamine are currently the primary pharmacological treatments available to improve cognition and associated neuropsychiatric symptoms in Lewy body diseases. Other possible pharmacological strategies include increasing acetylcholine release with 5-HT4 agonists or directly stimulating cholinergic receptors with muscarinic and nicotinic agonists. The side effect profile of muscarinic agonists is a deterrent to their future study, but 5-HT4 and nicotinic agonists deserve further investigation. Targeting the basal forebrain with either deep brain stimulation (DBS)- or cell-based therapies is another strategy to mitigate cortical cholinergic deficiency. Before NBM DBS studies continue, it will be important to resolve issues related to targeting, stimulation pattern, and duration. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations. [ABSTRACT FROM AUTHOR]

A series of new Olaparib derivatives was designed and synthesized, and their inhibitory activities against poly (ADP-ribose) polymerases-1 (PARP-1) enzyme and cancer cell line MDA-MB-436 in vitro were evaluated. The results showed that compound 5l exhibited the most potent inhibitory effects on PARP-1 enzyme (16.10 ± 1.25 nM) and MDA-MB-436 cancer cell (11.62 ± 2.15 μM), which was close to that of Olaparib. As a PARP-1 inhibitor had been reported to be viable to neuroprotection, in order to search for new multitarget-directed ligands (MTDLs) for the treatment of Alzheimer's disease (AD), the inhibitory activities of the synthesized compounds against the enzymes AChE (from electric eel) and BChE (from equine serum) were also tested. Compound 5l displayed moderate BChE inhibitory activity (9.16 ± 0.91 μM) which was stronger than neostigmine (12.01 ± 0.45 μM) and exhibited selectivity for BChE over AChE to some degree. Molecular docking studies indicated that 5l could bind simultaneously to the catalytic active of PARP-1, but it could not interact well with huBChE. For pursuit of PARP-1 and BChE dual-targeted inhibitors against AD, small and flexible non-polar groups introduced to the compound seemed to be conducive to improving its inhibitory potency on huBChE, while keeping phthalazine-1-one moiety unchanged which was mainly responsible for PARP-1 inhibitory activity. Our research gave a clue to search for new agents based on AChE and PARP-1 dual-inhibited activities to treat Alzheimer's disease. [ABSTRACT FROM AUTHOR]

A series of new coumarin/1,2,4-oxadiazole hybrids were synthesized and evaluated for cholinesterase inhibitory and neuroprotective activities. Among them, enantiomers 5u and 5v showed potent hBChE inhibitory activity with IC50 values of 8.17 and 9.56 μM, respectively, and also exhibited good selectivity for hBChE over hAChE by 9.49- and 7.58-fold, respectively. In addition, both compounds could protect SH-SY5Y cells against Aβ25–35-induced neurotoxicity. The preliminary bioassay results provided a new chemotype for multifunctional anti-Alzheimer's disease agents and continuing investigation into compounds 5u and 5v is warranted. [ABSTRACT FROM AUTHOR]

Phytochemical investigation on the roots of Swietenia macrophylla yielded one new pharagmalin-type limonoid named 2-dehydroxyl-swietephragmin C (1) and one new xanthone, 1,5-dihydroxy-6-methoxy-6′,6′-dimethyl-2H-pyrano[2′,3′:3,2]xanthone (2), in addition to three known compounds. The structures of the new compounds were unambiguously determined by comprehensive spectroscopic methods (NMR, UV, IR, MS), as well as by comparison with the reported data in the literature. Xanthones were reported from Swietenia genus for the first time. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple pathological consequences such as oxidative stress, inflammation, apoptosis, cholinergic deficit, amyloid plaques, and tangles formation. Hence, development of drugs with multiple targets will be effective in the treatment of AD. The present study aims at evaluation of the neuroprotective effect of Gelidiella acerosa against amyloid beta 25–35 (Aβ 25–35) induced toxicity in PC12 cells. The antioxidative effect was evaluated by monitoring levels of antioxidant enzymes. Protection against ROS-induced damage was assessed by the measurement of lipid peroxidation, protein carbonyl content (PCC), 2′,7′–dichlorofluorescein diacetate (DCFH-DA) fluorescence, and nitric oxide (NO) production. The cholinesterase (ChE) inhibitory activity was also evaluated. The antiapoptotic activity was verified by caspase-3 activity. The results of antioxidant assays suggest that G. acerosa significantly (P <.05) restores the levels of antioxidant enzymes. Moreover, the seaweed extract was found to prevent the formation of intracellular ROS induced by Aβ 25–35 and thereby protects PC12 cells from macromolecular damage. The study demonstrated that G. acerosa inhibits ChE activity significantly (P <.05) in PC12 cells. The significant decrease (P <.05) in the level of caspase-3 activity indicates that the seaweed has anti-apoptotic activity. Hence, the outcome of this study signifies the neuroprotective effect of G. acerosa targeting multiple pathological consequences of AD. [ABSTRACT FROM AUTHOR]

The anticholinesterase and antioxidant potential of methanol (ME), aqueous (AE), ethyl acetate (EA), and hexane (HE) fractions of whole plant of Cascuta reflexa was evaluated. The anticholinesterase activity was assessed by Ellman's method, while the antioxidant activity was estimated by DPPH radical scavenging and reducing power assays. Phytochemical analysis and acute toxicity studies were also performed. ME of the plant showed inhibition (IC50 = 0.024) that was comparable to ascorbic acid (IC50 = 0.02), while EA and AE fractions had the strongest antioxidant activity with lowest IC50 of 0.00097 and 0.0021 mg mL−1, respectively. In the reducing power assay, EA fraction of the plant had the highest reducing power with high flavonoid level. The hexane fraction of the plant showed the lowest antioxidant activity in both these assays and had the least flavonoid contents. The methanol extract (ME) was positive for the presence of tannins, saponins, phenols, and flavonoids and was safe up to 2000 mg kg−1. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate in vitro antioxidant, anticholinesterase and antidiabetic properties of Ouratea hexasperma (A. St.-Hil.) Baill. The inflorescence methanol extract and the ethyl acetate fraction of leaves and stems reported the highest Relative Antioxidant Capacity Index (RACI), whereas the dichloromethane fraction of leaves was the best inhibitor of α-amylase and α-glucosidase. Trans-3-O-methyl-resveratrol-2-C-β-glucoside, lithospermoside, 2,5-dimethoxy-p-benzoquinone, lup-20(30)-ene-3β,28-diol, 7-O-methylgenistein, apigenin and luteolin and amentoflavone were isolated from O. hexasperma. Resveratrol derivative was isolated for the first time in Ochnaceae family. Luteolin, followed by apigenin, reported the highest Relative Antioxidant Capacity Index and they were also the best inhibitors of α-glucosidase enzyme. [ABSTRACT FROM AUTHOR]

Chemical investigation on the cultures of the fungus Cordyceps spp., a strain from cell fusion between Cordyceps militaris and Cordyceps cicadae, resulted in the isolation of 13 compounds including 2 new ones named 2-(5-(3-oxobutyl) furan-2-yl) acetic acid (1) and cordycepone (2). Their structures were elucidated from the analysis of 1D/2D NMR and CD data. Among them, compounds 1, 7–9, at a concentration of 50 μg/ml, showed weak inhibitory activity against AChE. Moreover, compounds 6, 9, and 11 showed moderate inhibitory activity against the nematode Panagrellus redivivus with mortality ratio of 79.0, 71.7, and 72.3% at 2.5 mg/ml, respectively. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess in vitro the effects of sulphenamide and sulphonamide derivatives of metformin on the activity of human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), establish the type of inhibition, and assess the potential synergism between biguanides and donepezil towards both cholinesterases (ChEs) and the effects on the β-amyloid aggregation. Sulphonamide 5 with para-trifluoromethyl- and ortho-nitro substituents in aromatic ring inhibited AChE in a mixed-type manner at micromolar concentrations (IC50 = 212.5 ± 48.3 µmol/L). The binary mixtures of donepezil and biguanides produce an anti-AChE effect, which was greater than either compound had alone. A combination of donepezil and sulphonamide 5 improved the IC50 value by 170 times. Compound 5 at 200 µmol/L inhibited Aβ aggregation by ∼20%. In conclusion, para-trifluoromethyl-ortho-nitro-benzenesulphonamide presents highly beneficial anti-AChE and anti-Aβ aggregation properties which could serve as a promising starting point for the design and development of novel biguanide-based candidates for AD treatment. [ABSTRACT FROM AUTHOR]

Cholinesterases (ChEs) are enzymes that break down neurotransmitters associated with cognitive function and memory. We isolated cinnamic acids (1 and 2), indolinones (3 and 4), and cycloartane triterpenoid derivatives (5-19) from the roots of Cimicifuga dahurica (Turcz.) Maxim. by chromatography. These compounds were evaluated for their inhibitory activity toward ChEs. Compound 1 was determined to have an IC50 value of 16.7 ± 1.9 μM, and to act as a competitive inhibitor of acetylcholinesterase (AChE). Compounds 3, 4 and 14 were found to be noncompetitive with IC50 values of 13.8 ± 1.5 and 6.5 ± 2.5 μM, and competitive with an IC50 value of 22.6 ± 0.4 μM, respectively, against butyrylcholinesterase (BuChE). Our molecular simulation suggested each key amino acid, Tyr337 of AChE and Asn228 of BuChE, which were corresponded with potential inhibitors 1, and 3 and 4, respectively. Compounds 1 and 4 were revealed to be promising compounds for inhibition of AChEs and BuChEs, respectively. [ABSTRACT FROM AUTHOR]

UHPLC/ESI/MS identification of organic compounds is the first step in the majority of screening techniques for the characterization of biologically active metabolites in natural sources. This paper describes a method for the fast identification and characterisation of secondary metabolites in Leptocarpha rivularis DC. (Palo negro) extracts by HPLC/UV (DAD)-Mass Spectrometry (HPLC/MS). The plant is used for the treatment of several diseases since pre-hispanic Mapuche times. Thirty-seven compounds were detected in the aqueous edible extract for the first time including 4 sesquiterpenes, 10 flavonoids, 9 oxylipins, 2 organic acids, and 11 phenolic acids. In addition, phenolic content antioxidant and cholinesterase inhibitory activities were measured for the first time using the edible infusion. The total polyphenol content of the infusion was 230.76 ± 2.5 mmol GAE/kg dry weight, while the antioxidant activity was 176.51 ± 28.84; 195.28 ± 4.83; and 223.92 ± 2.95 mmol TE/kg dry weight, for the DPPH, ABTS, and FRAP assays, respectively. The cholinesterase inhibitory activity was 7.38 ± 0.03 and 5.74 ± 0.06 mmol GALAE/kg, for the inhibition of acetylcholinesterase AChE and BChE, respectively, showing that this plant is a candidate for the isolation of compounds that can be useful for the treatment of neurodegenerative diseases. Furthermore, this plant could serve also as a raw material for the production of dietary supplements, due to its content of polyphenolic compounds. [ABSTRACT FROM AUTHOR]

Finding a new type of cholinesterase inhibitor that would overcome the brain availability and pharmacokinetic parameters or hepatotoxic liability has been a focus of investigations dealing with the treatment of Alzheimer’s disease. Isothiocyanates have not been previously investigated as potential cholinesterase inhibitors. These compounds can be naturally produced from their glucosinolate precursors, secondary metabolites widely distributed in our daily Brassica vegetables. Among 11 tested compounds, phenyl isothiocyanate and its derivatives showed the most promising inhibitory activity. 2-Methoxyphenyl ITC showed best inhibition on acetylcholinesterase with IC50 of 0.57 mM, while 3-methoxyphenyl ITC showed the best inhibition on butyrylcholinesterase having 49.2% at 1.14 mM. Assessment of the antioxidant efficacy using different methods led to a similar conclusion. The anti-inflammatory activity was also tested using human COX-2 enzyme, ranking phenyl isothiocyanate, and 3-methoxyphenyl isothiocyanate as most active, with ∼99% inhibition at 50 μM. [ABSTRACT FROM AUTHOR]