Inhibition Of Cholinesterase Enzymes Research Articles

Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents.

Benzimidazole-based pyrrole/piperidine analogs (1-26) were synthesized and then screened for their acetylcholinesterase and butyrylcholinesterase activities. All the analogs showed good to moderate cholinesterase activities. Synthesized compounds (1-13) were screened in cholinesterase enzyme inhibition assays and showed AChE activities in the range of IC50 = 19.44 ± 0.60 µM to 36.05 ± 0.4 µM against allanzanthane (IC50 = 16.11 ± 0.33 µM) and galantamine (IC50 = 19.34 ± 0.62 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 21.57 ± 0.61 µM to 39.55 ± 0.03 µM as compared with standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Similarly, synthesized compounds (14-26) were also subjected to tests to determine their in vitro AChE inhibitory activities, and the results obtained corroborated that all the compounds showed varied activities in the range of IC50 = 22.07 ± 0.13 to 42.01 ± 0.02 µM as compared to allanzanthane (IC50 = 20.01 ± 0.12 µM) and galantamine (IC50 = 18.05 ± 0.31 µM) and varied BuChE inhibitory activities, with IC50 values in the range of 26.32 ± 0.13 to 47.03 ± 0.15 µM as compared to standard allanzanthane (IC50 = 18.14 ± 0.05 µM) and galantamine (IC50 = 21.45 ± 0.21 µM). Binding interactions of the most potent analogs were confirmed through molecular docking studies. The active analogs 2, 4, 10 and 13 established numerous interactions with the active sites of targeted enzymes, with docking scores of -10.50, -9.3, -7.73 and -7.8 for AChE and -8.97, -8.2, -8.20 and -7.6 for BuChE, respectively.

New Imidazo[1,2-a]pyridin-2-yl Derivatives as AChE, BChE, and LOX Inhibitors; Design, Synthesis, and Biological Evaluation

Background: Inhibition of cholinesterase enzyme has been recognized as an important target in the symptomatic treatment of Alzheimer’s disease. Objective: In the current work, a series of new N-(4-(imidazo[1,2-a]pyridin-2-yl)phenyl)cinnamamide derivatives were synthesized and their inhibitory activities against acetyl cholinesterase, butrylcholines terase, and Lipoxygenase were evaluated. Methods: The target compounds were synthesized as the literature reported with some modifications. The AChE, BChE, and LOX inhibitory activities of the synthesized compounds were evaluated using in vitro methods. The docking and kinetic studies were performed for the most potent compounds to evaluate the inhibition mechanism. Results: The structural elucidation of the synthesized imidazo-pyridine derivatives was performed by different spectroscopic techniques including IR, NMR, and Mass. Most of the synthesized compounds demonstrated good AChE, BChE, and LOX inhibitory activities. The most active AChE, BChE, and sLOX-1 inhibitors were found for compounds 4a, 4g, and 4l, respectively. The docking study also revealed that the three compounds, 4a, 4g, and 4l, have important binding interactions with the AChE, BChE, and sLOX-1 enzyme active sites, respectively. Conclusion: The results of current study shows imidazo[1,2-a]pyridine derivatives have potential for development of novel drug candidate for AD as AChE, BChE and sLOX-1 inhibitors.

Constituents and Selective BuChE Inhibitory Activity of the Essential Oil from Hypericum aciculare Kunth.

A potential source of new inhibitors of cholinesterase enzymes are certain compounds of natural plant origin; therefore, in the study described herein we have determined the chemical composition and the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the essential oil (EO) steam distilled from aerial parts of Hypericum aciculare, which was collected in southern Ecuador. The oil qualitative and quantitative composition was determined by GC-FID and GC-MS using a non-polar and a polar chromatographic column. A total of fifty-three constituents were identified, that accounted for about 98% of the EO content. The hydrocarbon n-nonane (16.4-28.7%) and the aldehyde n-decanal (20.7-23.1%) were the predominant oil constituents. In addition, the EO showed significant inhibition of BuChE (IC50 = 28.3 ± 2.7 μg/mL) and moderate activity towards AChE (IC50 = 82.1 ± 12.1 µg/mL). Thus, the EO from H. aciculare aerial parts is an interesting candidate to investigate the mechanism of selective ChE inhibition by the two ChE enzymes with the aim to discover potential targets to control the progression of the Alzheimer's disease (AD).

Assessment of exposure to pesticides and the knowledge, attitude and practice among farmers of western Bhutan.

An estimated 69% of the population of Bhutan is engaged in agriculture. Farmers are exposed to a wide variety of pesticides during the preparation, transport, storage, mixing and application of pesticides posing a significant health risk. A controlled cross-sectional study of farmers in selected sites of Bhutan was conducted to characterize the level of exposure to pesticides and assess their knowledge attitude and practice on the safe handling of pesticides. A total of 399 participants were enrolled in the study comprising of 295 exposed farmers and 104 healthy and unexposed controls. A structured investigator administered questionaries was used to assess their Knowledge, Attitude and practice, and their blood samples were taken for measuring Acetyl Cholinesterase enzyme activity level. There was a significant difference between the Acetyl Cholinesterase enzyme inhibition of exposed and non-exposed control groups observed in the study (P < 0.001). Of the total of 295 farmers, 62 (21.01%) had severe enzyme inhibition of >30% as compared to the unexposed group. Safety practices of handling pesticides were low. The most common symptoms self-reported were headache (OR 1.08, 0.60-1.93) and neurological problems like forgetfulness, lack of concentration (OR 1.12, 0.50-2.48) and increased tiredness (OR 1.075, 0.52-2.19) that were significantly associated with the enzyme inhibition. In addition, we record a very low level of knowledge (17.0%), a fair attitude (63.0%) and poor practice (35.0%) on the safe handling and management of pesticides. This pilot study provides indication of exposure to pesticides in the selected sites of the country. Furthermore, it provides evidence for public health interventions by identifying the exposure patterns and pathways of individuals most at risk in the farming communities of the country. Surveillance and bio-monitoring programs are deemed necessary.

Anti-AChE and Anti-BuChE Screening of the Fermentation Broth Extracts from Twelve Aspergillus Isolates and GC-MS and Molecular Docking Studies of the Most Active Extracts.

Nowadays, the administration of cholinesterase enzyme (acetylcholinesterase: AChE and butyrylcholinesterase: BuChE) inhibitors is very common for the symptomatic treatment of Alzheimer's disease and the other forms of dementia and CNS disorders. In this paper, the anti-AChE and anti-BuChE activities of the fermentation broth ethyl acetate extracts from twelve Aspergillus isolates were evaluated by Ellman method. The results showed that A1 (Aspergillus flavus) and A5 (Aspergillus tubingensis, isolate 1) extracts with IC50 values of 46.77 μg/mL and 75.85 μg/mL possess the greatest ability to inhibit AChE and BuChE, respectively. GC-MS analysis of the extracts (A1 and A5) demonstrated that two alkaloids named 14-methyl-16-azabicyclo[10.3.1]hexadeca-1(15),12(16),13-triene (MAHT) and 6-chloro-2-methyl-7,8,9,10-tetrahydro-phenanthridine (CMTP) account for the highest percentage of A1 (26.95%) and A5 (25.5%) extracts, respectively. A 2-pyrazoline derivative, 5-hydroxy-3-(4-pyridinyl)-5-trifluoromethyl-1-(2,4,6-trimethylphenoxyacetyl)- (PHPTT), also constituted the high percentage (9.54%) of A5 extract. The anticholinesterase and neuroprotective effects of some 2-pyrazoline derivatives have been previously reported. The interaction study of MAHT with human AChE and CMTP and PHPTT with human BuChE using molecular docking indicated that these alkaloids bind to the active site gorge of the enzymes with high affinity. The best docking scores of MAHT, CMTP, and PHPTT were -7.1, -8.2, and -9.7 kcal/mol, respectively.

Basics of Alzheimer’s Disease and Dementia

Alzheimer’s Disease (AD) is a disorder that causes degeneration of the cells in the brain and it is the main cause of dementia, which is characterized by a decline Independence in an individual’s daily activities. AD is considered a multifactorial disease. Two main hypotheses have been proposed as the cause of AD. The cholinergic hypothesis and the amyloid hypothesis. In addition, several risk factors have been implicated in this disease, including aging, genetic factors, head trauma, vascular disease, infections, and environmental factors. Currently, there are only two classes of drugs approved for the treatment of AD, including cholinesterase enzyme inhibitors and N-Methyl-D-Aspartic Acid (NMDA) antagonists, which are not associated with AD symptoms or disease. Prevent. Today, research is focused on understanding the pathology of AD by targeting multiple mechanisms such as alteration of AD course. This review describes the drugs currently available and future theories for the development of new treatments for AD, including Disease-Modifying Therapies (DMTs), chaperones, and natural products.

Ultrasound-Assisted Synthesis of Piperidinyl-Quinoline Acylhydrazones as New Anti-Alzheimer's Agents: Assessment of Cholinesterase Inhibitory Profile, Molecular Docking Analysis, and Drug-like Properties.

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes (4a,b) and (un)substituted aromatic acid hydrazides (7a-m) provided facile access to target compounds (8a-m and 9a-j) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1H- and 13C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c, also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).

Phytochemical Characterization and In Vitro and In Silico Biological Studies from Ferns of Genus Blechnum (Blechnaceae, Polypodiales)

The genus Blechnum represents one of the most ecologically and therapeutically important groups of ferns that grow in tropical, subtropical and temperate regions. In this work, the chemical fingerprint of lyophilized extracts of Blechnum chilense, B. hastatum, B. magellanicum and B. penna-marina species, the determination of their antioxidant activity through ORAC, FRAP and DPPH assays and inhibition of cholinesterase enzymes (AChE and BChE), and an in silico analysis of selected majority compounds on cholinesterase enzymes were identified. Nineteen compounds were recorded for B. chilense, nine in B. hastatum, seventeen in B. magellanicum and seventeen in B. penna-marina by liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). The content of phenolic compounds, flavonoids, antioxidant activity and enzyme inhibition were variable among species, with best results for B. penna-marina. Molecular docking evidenced low toxicities, significant pharmacokinetic properties, and significant binding affinities of the tested compounds for the AChE and BChE enzymes. These fern species show high diversity of bioactive compounds and represent a promising resource in phytotherapy, especially for their optimal levels of phenolic compounds that support their antioxidant activity.

Therapeutic potential of 1,3,4-oxadiazoles as potential lead compounds for the treatment of Alzheimer's disease.

Monoamine oxidase and cholinesterase enzymes are important targets for the treatment of several neurological diseases especially depression, Parkinson disease and Alzheimer's. Here, we report the synthesis and testing of new 1,3,4-oxadiazole derivatives as novel inhibitors of monoamine oxidase enzymes (MAO-A and MAO-B) and cholinesterase enzymes (acetyl and butyryl cholinesterase (AChE, BChE). Compounds 4c, 4d, 4e, 4g, 4j, 4k, 4m, 4n displayed promising inhibitory effects on MAO-A (IC50: 0.11-3.46 μM), MAO-B (IC50: 0.80-3.08 μM) and AChE (IC50: 0.83-2.67 μM). Interestingly, compounds 4d, 4e and 4g are multitargeting MAO-A/B and AChE inhibitors. Also, Compound 4m displayed promising MAO-A inhibition with IC50 of 0.11 μM and high selectivity (∼25-fold) over MAO-B and AChE enzymes. These newly synthesized analogues represent promising hits for the development of promising lead compounds for neurological disease treatment.

Evaluation of derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases and their antioxidant activity: In vitro, in silico, and kinetics studies

In search of potent inhibitors of cholinesterase enzymes and antioxidant agents, synthetic derivatives of dihydroquinazolin-4(1H)-one (1?38) were evaluated as potential anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitions and radical (DPPH and ABTS) scavenging activities. The structure?activity relationship (SAR) was mainly based on the different substituents at the aryl part which showed a significant effect on the inhibitory potential of enzymes and radical scavenging activities. The kinetic studies of most active compounds showed a noncompetitive mode of inhibition for AChE and a competitive mode of inhibition for the BChE enzyme. Additionally, molecular modelling studies were carried out to investigate the possible binding interactions of quinazolinone derivatives with the active site of both enzymes.

Grid-Type Quaternary Metallosupramolecular Compounds Inhibit Human Cholinesterases through Dynamic Multivalent Interactions.

We report the implementation of coordination complexes containing two types of cationic moieties, i. e. pyridinium and ammonium quaternary salt, as potential inhibitors of human cholinesterase enzymes. Utilization of ligands containing NNO-coordination site and binding zinc metal ion allowed mono- and tetra-nuclear complexes to be obtained with corner and grid structural type, respectively, thus affecting the overall charge of the compounds (from +1 to +8). We were able to examine for the first time the multivalency effect of metallosupramolecular species on their inhibitory abilities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Importantly, resolution of the crystal structures of the obtained enzyme-substrate complexes provided a better understanding of the inhibition process at the molecular level.

Monitoring the Activity and Inhibition of Cholinesterase Enzymes using Single-Walled Carbon Nanotube Fluorescent Sensors.

Cholinesterase enzymes are involved in a wide range of bodily functions, and their disruption is linked to pathologies such as neurodegenerative diseases and cancer. While cholinesterase inhibitors are used as drug treatments for diseases such as Alzheimer and dementia at therapeutic doses, acute exposure to high doses, found in pesticides and nerve agents, can be lethal. Therefore, measuring cholinesterase activity is important for numerous applications ranging from the search for novel treatments for neurodegenerative disorders to the on-site detection of potential health hazards. Here, we present the development of a near-infrared (near-IR) fluorescent single-walled carbon nanotube (SWCNT) optical sensor for cholinesterase activity and demonstrate the detection of both acetylcholinesterase and butyrylcholinesterase, as well as their inhibition. We show sub U L–1 sensitivity, demonstrate the optical response at the level of individual nanosensors, and showcase an optical signal output in the 900–1400 nm range, which overlaps with the biological transparency window. To the best of our knowledge, this is the longest wavelength cholinesterase activity sensor reported to date. Our near-IR fluorescence-based approach opens new avenues for spatiotemporal-resolved detection of cholinesterase activity, with numerous applications such as advancing the research of the cholinergic system, detecting on-site potential health hazards, and measuring biomarkers in real-time.

Synthesis, biological evaluation and computational investigations of S-benzyl dithiocarbamates as the cholinesterase and monoamine oxidase inhibitors

The current study was aimed to identify the selective and multi-targeted inhibitors of cholinesterase and monoamine oxidase enzymes. For this purpose, a novel class of multi-targeted compounds i.e., S-benzyl dithiocarbamates (1-30) was synthesized via a single pot reaction and the structures were characterized via NMR (1H and 13C), FT-IR and high-resolution mass spectrometry (HRMS). Moreover, the purity of the final products was determined using thin-layer chromatography (TLC). The compounds were evaluated for their inhibitory potential against cholinesterases (ChE) and monoamine oxidases (MAO). Among all derivatives, compound 5 (2-(trifluoromethyl) benzyl azepane-1-carbodithioate) depicted the maximum inhibition of AChE and BChE enzyme with an IC50 value of 4.37±0.94 and 14.9±1.11, respectively. The derivative 11, expressed maximum inhibition of MAO-A and MAO-B with an IC50 value of 1.14±0.03 and 1.01±0.16 µM, respectively. Whereas, compound 16 exhibited maximum inhibitory potential against all four targeted enzymes i.e., AChE, BChE, MAO-A and MAO-B with an IC50 value of 1.39±0.07 µg/ mL, 1.52±0.14 µg/ mL, 44.9±1.54 µM and 2.85±0.21 µM, respectively. The chemical reactivity profile of the potent derivatives were evaluated through density functional theory studies (DFT) where it was found that compound 5, 6 and 11 possessed reactive character due to narrow LUMO/HOMO energy gap. In addition, Molecular docking studies revealed excellent docking scores and produced sable protein-ligand complexes. The stability of protein-ligand complex was affirmed by molecular dynamic simulations which revealed stable and equilibrated trajectories of simulated complexes. The findings of in-vitro and in-silico studies suggested compound 16 as a promising multi-targeted compound that can be act as lead molecule for the treatment of AD.

Design, synthesis and structure-activity relationship studies of 3-phenylpyrazino[1,2-a]indol-1(2H)-ones as amyloid aggregation and cholinesterase inhibitors with antioxidant activity

A group of novel fused tricyclic derivatives based on a pyrazino[1,2-a]indol-1(2H)-one ring scaffold possessing a C3 phenyl substituent were designed, synthesized and evaluated as multi-target-directed-ligands (MTDLs) for Alzheimer's disease (AD). The biochemical assays were carried out to determine their inhibition activity toward i) amyloid peptide aggregation (Aβ40 and Aβ42), ii) acetyl and butyrylcholinesterase (AChE and BuChE) enzyme inhibition and iii) evaluation of their antioxidant properties. These studies identified several 3-phenylpyrazino[1,2-a]indol-1(2H)-one derivatives that exhibited multi-targeting activity capable of preventing amyloid aggregation (Aβ40 and Aβ42 inhibition range ​= ​10–89.5% at 25 ​μM), inhibition of cholinesterase enzymes (AChE and BuChE IC50 range ​= ​1.6–21 ​μM) and antioxidant activity (24–55% inhibition at 25 ​μM). The lead compound 5i (3-(3,4-dimethoxyphenyl)pyrazino[1,2-a]indol-1(2H)-one), exhibited multi-targeting activity with excellent inhibition of Aβ40 and Aβ42 aggregation (85% and 90% inhibition at 25 ​μM), dual inhibition of human cholinesterase enzymes (hAChE IC50 ​= ​7.5 ​μM; hBuChE IC50 ∼ 15 ​μM) and antioxidant property (∼39% inhibition at 25 ​μM). Compound 5i did not exhibit toxicity in mouse HT22 mouse hippocampal neuronal cells at 25 ​μM. In addition, 5i was able to prevent Aβ42 mediated cytotoxicity in the mouse hippocampal neuronal HT22 ​cells (77% cell viability). In the in vitro PAMPA-BBB permeation assay, compound 5i and 5a showed permeability values Pe ​= ​2.25 ​× ​10−6 ​cm/s and 6.20 ​× ​10−6 ​cm/s respectively, suggesting their ability to get into brain. These structure-activity studies demonstrate that the fused tricyclic pyrazino[1,2-a]indol-1(2H)-one template is capable of binding to Aβ (Aβ40 and Aβ42), and human cholinesterase enzymes (hAChE and hBuChE), and that a C3 3,4-diOMe-phenyl is a novel Aβ-binding pharmacophore that can be incorporated in the design of anti-AD agents.

Synthesis multicomponent based on o‐tolyl‐isocyanide; cholinesterase inhibitors and computational studies

Isocyanide-based multicomponent reactions turn out to be interesting synthetic strategies, with highly valued advantages such as atomic economy, selectivity, among others. Furthermore, Isocyanide-based multicomponent reactions have been shown to generate a wide range of products with significant biological activity. Recently, it has been described that the compounds of the Isocyanide-based multicomponent reactions product could be inhibitors of cholinesterase enzymes, acetylcholinesterase, and butyrylcholinesterase. cholinesterase enzymes have aroused great interest as pharmacological targets in the treatment of Alzheimer's disease, which is a disease that affects millions of people in the world, and its effects become disabling for those who suffer from it since it mainly has consequences on memory and cognitive ability. In this work, using Isocyanide-based multicomponent reactions, we report a series of five new compounds, their characterization, and their potential inhibitory biological activity on acetylcholinesterase and butyrylcholinesterase by spectrophotometric analysis. Our studies revealed that the compounds have moderate inhibitory activities against acetylcholinesterase and butyrylcholinesterase. Interestingly, compounds 7a and 7e showed a higher affinity for butyrylcholinesterase. Particularly compound 7a proved to be the compound with the best activity of this series with an IC50 of 25.91 µM for butyrylcholinesterase, more than 62.22 times selective for butyrylcholinesterase than for acetylcholinesterase. The study of molecular docking and molecular dynamics revealed that the hydrophobic character of these compounds favors the interaction with BChE. The favored interactions for compounds 7a and 7e are with the hydrophobic residues Trp82, Trp231, Val288, Phe329, Thr120. In addition, the molecular electrostatic potential and pharmacokinetic predictions also showed that compounds 7a and 7e have free energy values close to galantamine in the complex with butyrylcholinesterase, among others. These analyzes will allow us in the future to establish some structural modifications that would enable, on this basis, to obtain compounds with better activity against cholinesterase enzymes.

Sensitivity of cholinesterase activity in juvenile giant freshwater prawn (Macrobrachium rosenbergii de Man, 1879) to organophosphate diazinon

Pesticides containing diazinon are frequently used in agriculture in the Vietnamese Mekong delta region leading to their potential residual occurrence in the environment. Under laboratory conditions, exposure to diazinon has been shown to result in adverse inhibition of cholinesterase enzyme (ChE) activity and subsequent death in several fish species. This study investigated a 96-h median lethal concentration (LC50) of diazinon concentrations from 0.08 to 1.25 mg/L on juvenile giant freshwater prawns (Macrobrachium rosenbergii de Man, 1879) in tanks in the laboratory. Inhibition of ChE in the flesh and in the eyes of the tested shrimps after exposed to diazinon concentrations of 2.7, 27, 67.5 μg/L equivalent to 1%, 10%, 25% LC50–96 h was calculated. The results indicated that diazinon was highly toxic to giant freshwater prawn with a low LC50–96 h of 270 μg/L. The activity of ChE in the flesh was more sensitive to diazinon than that in the eyes. Furthermore, in the future, the activity of ChE in the flesh or in the eyes of shrimps has potential to be used as biomarker for rapid recognition of diazinon contamination in water.

An Overview on the Aetiology and Treatment of Alzheimer's Disease

Alzheimer’s disease is a disease that mainly leads to the degeneration of cells in the brain and it causes dementia. This reduces thinking capacity and doesn't allow the person to be independently do their own work. Two main causes of AD are cholinergic and amyloid hypothesis. Other risk factors include age, genetics, infections in the brain etc. currently only two types of drugs can treat AD, cholinesterase enzyme inhibitors and NMDA antagonists, but these are only able to treat the symptoms not the whole disease. At this moment the researchers are trying to target several mechanisms such as abnormal tau protein metabolism, inflammation and damage in the cholinergic system.

Polyphenol Composition, Anticholinesterase and Antioxidant Potential of the Extracts of Clinopodium vulgare L.

Clinopidium vulgare L. (wild basil, Lamiaceae) is a well-known medicinal plant used in the traditional medicine in many countries. Medicinal plants present potential sources of bioactive compounds. Many of them are rich in polyphenol compounds that show biological potential in terms of protecting biological molecules from oxidation and in inhibition of cholinesterase enzymes, which may be significant in the treatment of diseases related to oxidative stress. In this work, we examined the chemical composition of Clinopodium vulgare L. hot water and methanol extract using spectroscopic and HPLC/DAD techniques. Using DPPH and FRAP methods the antioxidant activity was analyzed. The ability to protect proteins and lipids from oxidation was also determined as well as the ability of extracts to inhibit cholinesterase enzymes using Ellman's method. Analyzed extracts were rich in polyphenol compounds. Among 16 identified and quantified phenolic compounds dominant were: rosmarinic (26.63 and 34.21 mg/g) and ellagic acid (23.11 and 29.31 mg/g) of hot water and methanol extract, respectively. They show good antioxidant activity and good potential in protecting lipids from oxidation. The ability of extracts to inhibit enzyme acetylcholinesterase was weak, while inhibition of the butyrylcholinesterase was missing. Extracts show prooxidant activity in terms of protecting proteins from oxidation.

A New Mode of Thinfilm and Nanofiber for Burst Release of the Drug for Alzheimer Disease; A Complete Scenario from Dispersible Polymer to Formulation Methodology.

Alzheimer's Disease (AD) is usually caused by intellectual deterioration which occurs due to the degeneration of cholinergic neurons. Donepezil is employed for cholinesterase enzyme Inhibition (ChEI) to treat AD in a wider population. Over the years, researchers finding difficulties prompted through traditional dosage forms particularly in geriatric patience. To avoid swallowing difficulties brought about with the aid of the AD population, researchers majorly focused on Oral Thin-Film technology (OTF). This technology strongly eliminates issues caused by solid oral dosage forms. It is one of the quality strategies to alternate a drug that is used in the first-pass metabolism or pre systematic metabolism. The solubility of the drug is a bigger problem and it can expand by way of lowering particle size. Nanofibers are need of the day to minimize the drug particles at the submicron stage which can increase the drug release rate drastically. It can be prepared by Electrospinning technology by incorporating polymeric material into poorly soluble drugs. Mostly natural and biodegradable polymers prefer in all pharmaceutical preparations. Polymers employed for oral delivery should be stable, possess mucoadhesive properties, and should release the drug by diffusion, degradation, and swelling mechanism. The objective of the present review explains various thin-film and nanofiber formulations used for faster drug release in the treatment of Alzheimer's disease.

Bongardia chrysogonum (L.) Spach as a potential medicinal plant against cancer and Alzheimer’s disease management

Background and Aims: Bongardia chrysogonum (L.) Spach (Berberidaceae), an ancient medicinal plant in Eastern Mediterranean countries, is traditionally used for the treatment of epilepsy, hemorrhoids, urinary system infections and gastrointestinal disorders. This study was designed to evaluate potential neuroprotective and anticancer effects of different parts from B. chrysogonum. Material and Methods: Leaf, stem, and tuber parts of the plant were extracted and subjected to determine cholinesterase enzyme inhibitory potentials and anticancer activities. Enzyme inhibition assays were carried out to screen neuroprotective potentials, while the MTT assay was performed for evaluating anticancer activities of the extracts towards human lung carcinoma (A549), breast adenocarcinoma (MCF-7), brain glioma (C6), and non-tumorous human umbilical vein endothelial cell (HUVEC) lines. Results: Among the tested extracts, the highest enzyme inhibitory activity was exhibited by tuber-water extract (83.81±0.33% and 62.14±0.60% inhibition on AChE and BChE at 400 µg/mL p&lt;0.01, respectively), whilst the lowest enzyme inhibition was exerted by the tuber-chloroform extract. Moreover, the tuber part of the plant was found to have the most cytotoxic activity against all the cancer cells, and the best anticancer activity was determined in tuber ethanol extract against MCF-7 cells (IC50= 28.36±0.04, p&lt;0.01). Conclusion: To the best of our knowledge, this research is the first study that assessed the in vitro neuroprotective effect of the aerial parts and tuber extracts of the plant through inhibition of cholinesterase enzymes alongside an anticancer capacity towards human cancer cells. The results revealed that this plant is a good candidate for performing further clinical studies in cancer and neurodegenerative diseases.