Acetylcholinesterase Inhibitors Research Articles

Preventing Donepezil-Induced Adverse Effects Through N-acetylcysteine Co-Administration.

Drug-induced adverse symptoms affect patients' quality of life (QoL) during treatment. Understanding the underlying mechanisms of drug-induced adverse effects could help prevent them. As current drugs have limited effects in halting the progress of Alzheimer's disease (AD), patients are required to take these drugs over a long period. The main obstacles to long-term compliance are drug-elicited side effects that deteriorate patient QoL. Donepezil, the most popular acetylcholinesterase inhibitor (AChEI) drug for AD, induces various side effects, especially at high doses. This study aimed to identify a drug that can attenuate the side effects of donepezil and investigate the underlying mechanisms. Five-week-old Sprague-Dawley rats received daily oral donepezil and N-acetylcysteine (NAC) for four weeks. General symptoms following administration were monitored daily to address drug-related adverse effects. Cytosolic calcium influx and generation of reactive oxygen species (ROS) after drug treatment were measured in vitro using C2C12 myotubes. High-dose donepezil induced numerous adverse symptoms in male and female rats, which were markedly attenuated by co-treatment with NAC. NAC significantly reduced both acute and chronic muscle-related symptoms caused by donepezil. Additionally, in vitro studies showed that high-dose donepezil increased ROS and intracellular calcium ([Ca2+]i) levels in muscle cells, contributing to these adverse effects. NAC co-treatment dramatically reduced ROS and [Ca2+]i levels in muscle cells. Combined treatment with NAC effectively diminishes the adverse effects elicited by donepezil by regulating ROS and [Ca2+]i levels in the skeletal muscle, which could contribute to improving donepezil treatment in patients.

Nanodisc-associated acetylcholinesterase as a novel model system of physiological relevant membrane-bound cholinesterases. Inhibition by phenolic compounds

Acetylcholinesterase (AChE) plays a pivotal role in the cholinergic system, and its inhibition is sought after in a wide range of applications, from insect control to Alzheimer's disease treatment. While the primary physiological isoforms of AChE are membrane-bound proteins, most assays for discovering new, safer, and potent inhibitors are conducted using commercially available soluble isoforms, such as the electric eel AChE (eeAChE). In this study, we conducted a comparative analysis of the activity and selectivity to phenolic inhibitors of recombinant human AChE, eeAChE and a mutant variant of human AChE known as dAChE4. Despite numerous mutations, dAChE4 closely resembles its parental protein and serves as a suitable model for monomeric human AChE. We also established an in vitro system of membrane-bound AChE to create a model that closely mimics the physiological isoforms. This system ensures the proper work of the enzyme and allowed us to control the exact concentration of enzyme and lipids per assay.

Catalytic N-Alkylation of (Hetero)Aromatic Amines and Tandem Annulation Reactions.

A general and practical approach for N-alkylation of heteroaromatic amines with heteroaromatic alcohols is always challenging and rarely reported. Here, we designed and synthesized phosphine-free, robust, and efficient N,N-bidentate-Co(II) complexes for a universal N-alkylation of amines strategy. This present catalytic methodology can be applied to a wide range of substrates by varying alcohols, including aryl, aliphatic, acyclic, and cyclic groups, with heteroaromatic amines such as aminopyridine, 2-aminopyrimidine, and aminoquinoline to provide diverse monoalkylated organonitrogen compounds in good to excellent yields (108 examples). In addition, the utility of the developed catalytic protocol was also extended successfully for the dehydrogenative synthesis of biologically important quinoline derivatives (11 examples). Particularly, 8-aminoquinoline reacted differently with tandem N-alkylated-transfer hydrogenative byproduct (N-benzyl-1,2,3,4-tetrahydroquinolin-8-amine) was obtained, revealing the catalytic activity of the complex I. The reaction proceeded under environmentally benign conditions, which liberates water as the sole byproduct. Notably, a concise synthesis of acetylcholinesterase inhibitors (AChEIs) scaffolds as potential cognition enhancers illustrated the utility of the present protocol. Interestingly, various control and deuterium-labeled experiments were performed, suggesting that the reaction proceeds via the borrowing hydrogen pathway.

Association between Polypharmacy and Adverse Events in Patients with Alzheimer's Disease: An Analysis of the Japanese Adverse Drug Event Report Database (JADER).

Background and Objectives: Alzheimer's disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer's disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Materials and Methods: Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer's disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer's disease drug combinations, as well as the number of concomitant medications. Results: Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. Conclusions: In the treatment of Alzheimer's disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer's disease drugs and their combination patterns.

8634 Ogilvie Syndrome As A Rare Complication Of Metastatic Pheochromocytoma

Abstract Disclosure: S.K. Beeby: None. J.C. Marcayata, MD: None. D.P. Di Matteo, MD: None. F.F. Souza, MD: None. I.C. Souza, MD: None. M.F. Azevedo, MD: None. F.M. Coelho, MD: None. A. Latronico, MD: None. B.B. Mendonca: None. M.C. Fragoso: None. M.Q. Almeida: None. Background: Ogilvie's Syndrome (acute colonic pseudo-obstruction) is a rare manifestationof pheochromocytoma and paraganglioma. Its pathophysiology can be explained by thehypersecretion of catecholamines, which may reduce peristaltic activity of the gastrointestinaltract due to alpha-adrenergic stimulation. We present here the case of a patient with acuteintestinal pseudo-occlusion due to metastatic pheochromocytoma. Clinical Case: A 60-year-old male with local recurrence of pheochromocytoma presentedwith abdominal pain, anorexia, nausea, vomiting and constipation for 2 weeks. The patientunderwent left adrenalectomy and nephrectomy to resect a 7.5 cm pheochromocytoma 6years ago. On examination, his blood pressure was 186 x 122 mmHg and heart rate was 112bpm. There was abdominal distention and diminished bowel sounds. Diaphoresis was notedmainly at night. Plasma fractionated metanephrines were markedly elevated, withnormetanephrine of 50.2 nmol/L (reference range <0.9 nmol/L) and metanephrine of 0.4nmol/L (reference range <0.5 nmol/L). Abdominal CT scan showed neoplastic lesionoccupying the left adrenal space, measuring 9.0 x 5.0 x 5.5 cm, infiltrating the spleen andpancreatic tail, and para-aortic and aorto-caval lymphomegaly of 1.3 cm. The large intestinewas distended with gas and lodged stool without evident obstructive factors. He was thenstarted on a high-sodium diet and alpha-blocker doxazosin 2 mg tid and propranolol 40 mgtid. Due to the presence of significant orthostatic hypotension, amlodipine 5 mg bid wasinitiated to control blood pressure. Laxatives and enemas were not effective in relieving hissymptoms and decompression with a nasogastric tube was necessary. The patient was thenput on subcutaneous neostigmine, an acetylcholinesterase inhibitor. Unfortunately, colonicpseudo-obstruction did not revert with pharmacological treatment and parenteral nutritionwas started. Since a complete tumor resection was not possible due to extensive invasion oflarge vessels, systemic cytotoxic chemotherapy (cyclophosphamide, vincristine anddacarbazine) was initiated as an attempt to treat the colonic pseudo-obstruction. Clinical lessons: Functioning pheochromocytoma and paraganglioma should be consideredin the differential diagnosis of constipation and acute intestinal obstruction, particularly whenaccompanied by other signs and symptoms of catecholamine excess. This condition should bepromptly diagnosed and managed, as it can lead to bowel perforation with seriouscomplications. Medical management includes alpha-blocking agents and, when feasible,tumor resection has been associated with good response. Support: This work was supported by Sao Paulo Research Foundation (FAPESP) grant2019/15873-6 (to M.Q. Almeida). M.Q.A was also supported by National Council forScientific and Technological Development (CNPq) 304091/2021-9. Presentation: 6/1/2024

Investigating in vitro anticholinergic potential (anti-AChE and anti-BuChE) of Chaenomeles leaves extracts and its phytochemicals including chlorophylls, carotenoids and minerals.

The goal of this work was to evaluate the chemical constitution and health-promoting potential of 12 varieties of Chaenomeles × superba, speciosa and japonica leaves. Carotenoids, chlorophylls, triterpenes, sugars, polyols and acids were analyzed quantitatively and qualitatively using high pressure liquid chromatography (LC) coupled with mass spectrometry (MS), while the mineral profile was determined using atomic absorption spectroscopy (AAS). Moreover, the in vitro anticholinergic potential (inhibition of acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE)) and antioxidant (ABTS, FRAP, ORAC) capacity were evaluated. For the first time in Chaenomeles genotypes 26 carotenoid derivatives and 22 chlorophyll derivatives were identified. Some varieties contained high amounts of carotenoids and chlorophylls (Ch. × superba 'Colour Trail', 'Nicoline', 'Pink Lady', 'Texas Scarlet'), and triterpenes (Ch. speciosa 'Simonii', 'Rubra', and Ch. × superba 'Colour Trail', 'Nicoline') and showed high ORAC antioxidant (Ch. × superba 'Pink Lady' and Ch. speciosa 'Simonii') and anticholinergic (Ch. speciosa species) activity. The studied leaves also contained sugars (3.1 to 16.5mg/100g), organic acids (3.9-8.1g/100g), and minerals (Ca, Cu, Fe, K, Mg, Mn, Na, and Zn). In conclusion, Chaenomeles leaves show potential as a new source for the production of nutraceuticals, as well as for medical and/or cosmetic purposes.

Biogenic synthesis of AgNPs via polyherbal formulation: Mechanistic neutralization and toxicological impact on acetylcholinesterase from Bungarus sindanus venom.

This study aims to examine the biogenic production, characterization, and anti-acetylcholinesterase (AAChE) properties of polyherbal formulation PHF-extract-synthesized silver nanoparticles (PHF-AgNPs). The Elapidae snake Bungarus sindanus has extremely dangerous venom for humans and contains a high amount of AChE (acetylcholinesterase). Inhibiting AChE leads to acetylcholine buildup, affecting neurotransmission. The study tested silver nanoparticles as AChE inhibitors using kinetics. Their production was confirmed through ultraviolet (UV) spectrometry at 425 nm (SPR peak of 1.94), and stabilizing functional groups were identified via Fourier transform infrared spectroscopy (FT-IR). The average length of 20 nm was confirmed by analyzing the scanning electron microscopy (SEM) data. Energy-dispersive X-ray spectroscopy (EDX) identified silver as the primary component of PHF-AgNPs (26%). Statistical analysis showed that the activity of AChE in krait venom decreased by up to 45% and 37% at a given dose of ACh (0.5 mM) by PHF and AgNPs, respectively. Utilizing the Lineweaver-Burk plot for kinetic analysis, a competitive type of inhibition is found. RESEARCH HIGHLIGHTS: Successfully synthesized PHF-extract-induced silver nanoparticles (PHF-AgNPs) demonstrated through UV spectrometry and characterized as crystalline with an average size of 45 nm by X-ray diffraction. PHF-AgNPs effectively inhibited acetylcholinesterase (AChE), an enzyme critical in neurotransmission, reducing its activity in krait venom by up to 45% at certain concentrations. Kinetic analysis revealed that the inhibition mechanism of AChE by PHF-AgNPs is competitive, offering potential for therapeutic applications in neurologically related conditions.

Assessment of the Interaction of Acetylcholinesterase Binding with Bioactive Compounds from Coffee and Coffee Fractions Digested In Vitro in the Gastrointestinal Tract.

The aim of the study was to evaluate the degree of acetylcholinesterase (AChE) inhibition by green and light- and dark-roasted coffee extracts and their fractions after digestion in a simulated gastrointestinal tract. The analysis was carried out using isothermal titration calorimetry, molecular docking, and dynamics simulations. The results showed that 3-O-caffeoylquinic acid binds strongly to AChE through hydrogen interactions with the amino acids ARG289A, HIS440A, and PHE288A and hydrophobic interactions with TYR121A in the active site of the enzyme. The Robusta green coffee extract (ΔG = -35.87 kJ/mol) and dichlorogenic acid fraction (ΔG = -19-29 kJ/mol) showed the highest affinity. Dichlorogenic acids (3,4-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, and 3,4-O-dicaffeoylquinic acid) have high affinity for AChE as single compounds (ΔG(ITC) = -48.99-55.36 kJ/mol, ΔG(LF/AD) = -43.38-45.38 kJ/mol). The concentration necessary to reduce AChE activity by 50% amounted to 0.22 μmol/μmol chlorogenic acids to the enzyme.

High-sensitive detection of organophosphate and carbamate pesticide residues in milk based on bioluminescence method

Organophosphorus pesticides (OPs) and carbamate pesticides (CBs) are the most commonly used pesticides in agricultural cultivation. The pesticide residues in plant products can easily enter dairy cows through feed, resulting in the pesticide low-concentration residues in milk. Traditional acetylcholinesterase (AChE) inhibition-based colorimetric methods have low sensitivity and could not satisfy the detection of low-concentrations of OPs and CBs residues in dairy products. In this study, we combined firefly luciferase (FLuc)-mediated bioluminescence with the inhibition of AChE-catalyzed substrate activity by pesticides to develop a highly sensitive and rapid method for detecting OPs and CBs residues in milk. AChE breaks down D-luciferin acetate to produce D-luciferin, which is recognized by the FLuc and emits luminescence in the presence of ATP. However, the presence of OPs and CBs inhibits AChE, causing the reduction or disappearance of the luminescence signal. The luminescence signal can be detected using a hand-held luminescence photometer, eliminating the need for large instrumentation. The AChE-FLuc system accurately detected OPs and CBs in milk within 30 min, with detection limits of 7.89 ng/mL and 1.75 ng/mL, respectively. The sensitivity of this method is approximately ten times higher than that of traditional AChE inhibition methods, meeting the pesticide residue limits in milk set by China and the European Union.

Investigating the phytochemical profile, biological potentials, morphological, and anatomical characteristics of Cyclotrichium origanifolium (Labill.) Manden. & Scheng. (Lamiaceae) from Turkey.

Cyclotrichium origanifolium, a plant widely used in Eastern and Southern Anatolia for culinary purposes, was subject of this study, which aimed to comprehensively evaluate its potential therapeutic applications. This research stands out due to its holistic approach, combining morpho-anatomical studies, chemical, and biological analyses to explore antioxidant, antidiabetic, anticholinesterase, genotoxic, and anti-genotoxic effects of methanolic and aqueous extracts, as well as flowering aerial part essential oil. It is a perennial plant, typically ranging from 10 to 40cm in height, with a suffrutescent and highly branched growth habit. Essential oils are produced within glandular trichomes. Oil, analyzed via GC-MS/MS, revealed 24 compounds accounting for 96.4% of oil, with isomenthone (52.4%), pulegone (23.4%), and β-pinene (9.5%) as predominant components. These findings are significant as they provide new insights into chemical composition of oils, particularly highlighting pharmacologically active compounds. Methanol extract exhibited superior antioxidant activity, correlated with high phenol and tannin content. Essential oil showed moderate inhibition of α-amylase (49.54%) and mild inhibition of acetylcholinesterase (11.84%) and butyrylcholinesterase (16.93%), suggesting potential in managing oxidative stress and neurodegenerative diseases. Study also conducted biosafety evaluations using Ames/Salmonella and Allium tests, essential for assessing genotoxic and antigenotoxic potential of natural products. Notably, significant antimicrobial effects were identified, particularly against Pseudomonas aeruginosa and Enterococcus faecalis. Comprehensive analysis and discovery of significant bioactivities position this research as a valuable contribution to field, distinguishing it from previous studies on similar species. This study provides a foundational understanding of morpho-anatomical, pharmacological, biological properties of plant, opening avenues for future research.

High-Speed Countercurrent Chromatography Isolation of Active Components from Evodia Rutaecarpa and Affinity Ultrafiltration Screening for Their Acetylcholinesterase Inhibitor Activity.

Acetylcholinesterase inhibitors from Evodia rutaecarpa were screened, prepared, and evaluated. To screen the lipophilic alkaloid active constituents in E. rutaecarpa, we improved and optimized an ultrafiltration system. Three acetylcholinesterase (AChE) inhibitors, dehydroevodiamine, evodiamine, and rutecarpine, were screened. Addressing the limitations of the traditional response surface methodology (RSM) for multiobjective screening, we integrated RSM with the Non-dominated Sorting Genetic Algorithm III to achieve the optimal extraction of these active ingredients. High-speed countercurrent chromatography was used to isolate the active components using a two-phase solvent system: n-hexane/ethyl acetate/methanol/water (3.0:2.5:3.5:2.0, v/v/v/v) and ethyl acetate/methanol/water (3.0:1.0:4.0, v/v/v). The nuclear magnetic resonance spectroscopy confirmed the structures of the compounds, and molecular docking and dynamics simulations assessed the inhibitory effects of the chemical components on AChE, which were consistent with the findings of the ultrafiltration experiments. We also confirmed the neuroprotective properties of these compounds against glutamate-induced apoptosis in PC12 cells. Overall, we achieved the systematic optimization of multitarget compound extraction and lipophilic alkaloid ultrafiltration screening, as well as preparation and activity validation, laying the groundwork for the development of AChE inhibitors from lipophilic alkaloids.

Quinindoline-Based Hybrid Compounds as New Inhibitors of Acetylcholinesterase: An In Vitro and Molecular Dynamics Simulations Study

Quinindoline-Based Hybrid Compounds as New Inhibitors of Acetylcholinesterase: An In Vitro and Molecular Dynamics Simulations Study

24P Improving gross motor function in pediatric centronuclear myopathy with acetylcholinesterase inhibitors: a case report

24P Improving gross motor function in pediatric centronuclear myopathy with acetylcholinesterase inhibitors: a case report

Fe3O4@MXene@PEI aerogel immobilized acetylcholinesterase for inhibitor screening from herbal plants

Screening of acetylcholinesterase (AChE) inhibitors is a common strategy in drug discovery for treating Alzheimer’s disease. Herein, AChE was immobilized onto magnetic polyethyleneimine-based MXene aerogels through both electrostatic interactions and covalent bonds, enabling its application in AChE activity assays and inhibitor screening of herbal plants. The composite was analyzed using a range of techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and Zeta potential analysis, to gain insight into its chemical and physical properties. The proposed Fe3O4@MXene@PEI-AChE composite exhibited enhanced temperature and pH stability, as evaluated by Ellman’s method, along with good reusability. The Michaelis Menten constant (Km) of the immobilized AChE was calculated to be 0.68 mmol/L. Additionally, an inhibition kinetic study was conducted to verify the feasibility of utilizing the immobilized enzyme to screen for inhibitors, with huperzine A employed as a model inhibitor. The proposed strategy was employed to compare the AChE inhibitory activity of 18 commonly used herbal medicines for treating AD, revealing both the aqueous and alcoholic extracts of Coptis chinensis as exhibiting the highest AChE inhibitory activity. Finally, the screening of AChE inhibitors in Coptis chinensis extracts were conducted by combining the proposed strategy with UPLC-Q-Orbitrap high resolution mass spectrometry. This study presents a feasible strategy for monitoring AChE activity and holds considerable potential for further exploration of AChE-inhibiting active ingredients in herbal medicines.

Searching for potential acetylcholinesterase inhibitors: a combined approach of multi-step similarity search, machine learning and molecular dynamics simulations.

Targeting acetylcholinesterase is one of the most important strategies for developing therapeutics against Alzheimer's disease. In this work, we have employed a new approach that combines machine learning models, a multi-step similarity search of the PubChem library and molecular dynamics simulations to investigate potential inhibitors for acetylcholinesterase. Our search strategy has been shown to significantly enrich the set of compounds with strong predicted binding affinity to acetylcholinesterase. Both machine learning prediction and binding free energy calculation, based on linear interaction energy, suggest that the compound CID54414454 would bind strongly to acetylcholinesterase and hence is a promising inhibitor.

A novel fluorescent sensor for evaluating pH changes in organophosphorus pesticides-treated cells and C. elegans

pH plays an important role in the evaluation of the healthy status in versatile circumstances. The fluctuation of pH could be affected by complex internal and external stimuli. Especially, the abnormal pH changes is a common characteristic of organophosphorus pesticides (OPs)-caused damage owing to the irreversible inhibition of acetylcholinesterase (AChE) activity. Therefore, the rapid and efficient detection of pH changes is of great significance for predicting the OPs poisoning in living system. However, quick and convenient detecting pH levels in living cells is still limited by the lack of effective chemical tools. Here, a novel fluorescent probe TH-1 based on ESIPT mechanism was synthesized, showing specific fluorescent effects in different pH solutions. Importantly, the AChE catalyzed the hydrolysis product of acetylthiocholine iodide (ATCh) and changed the pH of solution, which influence its fluorescent intensity. Moreover, the probe TH-1 was applied to detecting the pH levels in living cells and C. elegans, providing an efficient chemical sensor for revealing the potential mechanisms of OPs in physiological and pathological processes.

LC-MS and GC-MS Analyses on Green Algae Penicillus Capitatus: Cytotoxic, Antimicrobial and Anticholinesterase Activity Screening Enhanced by Molecular Docking & Dynamics and ADME Studies.

In this comprehensive screening study, the chemical composition, and cytotoxic, antimicrobial, and anticholinergic activities of the green algae Penicillus capitatus, collected from Antalya-Türkiye, were determined as in vitro and in silico. GC-MS analysis of the hexane extract revealed a high content of fatty acids, with hexadecanoic acid constituting half of the total fatty acid content. LC-HRMS analysis of the DCM:MeOH extract identified ascorbic acid as the most abundant compound, followed by (-)-epigallocatechin and salicylic acid. The DCM:MeOH extract exhibited potent cytotoxicity against MDA-MB-231 and MCF7 breast cancer cell lines, outperforming doxorubicin with lower IC50 values and a higher selectivity index. Additionally, the extract demonstrated significant antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, along with selective inhibition of acetylcholinesterase (hAChE) over butyrylcholinesterase (hBChE). Molecular docking and dynamics studies revealed that apigenin-7-O-glucoside and epigallocatechin form stable interactions with estrogen receptor alpha (ERα) and hAChE, suggesting their potential as inhibitors. In silico ADME studies indicated favorable pharmacokinetic profiles for the detected compounds, supporting their potential as drug candidates. The promising cytotoxic activity of the P. capitatus extracts, coupled with significant antimicrobial properties and selective hAChE inhibition, highlights their therapeutic potential for breast cancer treatment, infection management, and neurodegenerative disease intervention.

Exploring the chemical composition and biological effects of four Salvia hybrids: an innovative perspective on functional yields

AbstractGenus Salvia is considered one of the largest genera of family Lamiaceae with many recorded species and hybrids of valuable biological importance. This study involved the phytochemical characterization of four Salvia hybrids (KNM23 (S. fructicosa × S. officinalis), KNM101 (S. aramiensis × S. officinalis), KNM5 (S. aramiensis × S. officinalis) and KNM12 (S. fructicosa × S. officinalis)) through measuring their total phenolic content (TPC) and total flavonoid content (TFC) together with profiling through UPLC/MSn analysis followed by investigation of their antioxidant activities and enzyme inhibitory potential through different techniques. Hybrid KNM23 presented significantly high concentration of both phenolic and flavonoid, displaying a TPC of 92.10 mg GAE/g and a TFC of 50.85 mg RE/g. The UPLC/MSn profiling resulted in the tentative identification of one hundred eighty components from different phytochemical classes mainly flavonoids, phenolic acids, phenyl propanoids, tannins and many others. The antioxidant assay showed that hybrid KNM23, a hybrid of S. fruticosa and S. officinalis, exhibited the highest antioxidant activity in the DPPH, ABTS, and PBD assays, measuring 436.38 mmol TE/g, 543.65 mmol TE/g, and 3.20 mmol TE/g, respectively. KNM23 and KNM12 showed no inhibition of AChE and α‐glucosidase. However, KMN12 demonstrated highest BChE and tyrosinase 2.57 mg GALAE/g and 12.91 mg KAE/g, respectively. Our results suggest that the Salvia hybrids can be considered as natural sources of bioactive compounds in the development of health‐promoting applications.

Improvement of Visual Hallucinations With Donepezil in Charles Bonnet Syndrome Secondary to Vascular Pathology

ABSTRACTThere is a lack of high‐quality evidence for pharmacological treatment options for Charles Bonnet syndrome and guidelines do not recommend any particular pharmacological option. Here, a case is presented of an older age male who developed complex visual hallucinations following stroke and central retinal artery occlusion (one after the other leading to loss of vision in both eyes), thus indicative of CBS secondary to vascular pathology. This case demonstrates a sustained progressive improvement in hallucinations in CBS following the initiation of acetylcholinesterase inhibitor, donepezil.

Apocynaceae as a Potential Source for Acetylcholinesterase Inhibition in Symptomatic Regulation and Management of Alzheimer's Disease

: Memory loss or dementia is the key symptom of Alzheimer's disease (AD). In AD, significant interference in a progressive manner is observed in memory, behaviour, and cognitive abilities that affect the daily life of a person. At present, more than 50 million people are affected worldwide with Alzheimer's disease. Urgent attention is needed for the symptomatic regulation and management of this disease. The significant pharmacotherapy research in the last two decades gave only four drug compounds galanthamine, donepezil, rivastigmine, and memantine that inhibit the enzyme acetylcholinesterase (AChE) to elevate the availability of acetylcholine in the brain for symptomatic relief in AD patients. Plant-based AChE inhibitors from many plant families, mainly including Rutaceae, Papaveraceae, Apocynaceae, Rubiaceae, Amaryllidaceae, Liliaceae, Lycopodiaceae, Fabaceae, Lamiaceae, etc., have been characterized for the management of AD progression. AD progression is described by cholinergic, amyloid, Tau protein, oxidative stress, and neuroinflammatory hypothesis. To date, there is no comprehensive review in the literature that combined all plants of the Apocynaceae family showing anti-AChE activity. Therefore, the current review aims to present significant literature, especially on plant-derived compounds from the Apocynaceae family that inhibit AChE. The review compiled all plants showing potent anti-acetylcholinesterase activity. The anti-AChE activity of more than 30 plants is described, which may be potential targets to find new drug molecules by attracting the attention of researchers toward the Apocynaceae family. More than 8 species of genus Tabernaemontana of Apocynaceae have been investigated for indole alkaloids, demonstrating AChE inhibitory activity. The majority of anti-AChE compounds belong to the class of alkaloids.