Source Of Acetylcholinesterase Inhibitors Research Articles

Flustramine Q, a Novel Marine Origin Acetylcholinesterase Inhibitor from Flustra foliacea

The bryozoan Flustra foliacea produces a range of indole alkaloids, and some have shown weak antibiotic, muscle-relaxant and cytotoxic properties; however, most of them have not been tested for bioactivity. Many of these alkaloids possess a physostigmine scaffold, and physostigmine is a well-known acetylcholinesterase (AChE) inhibitor. AChE inhibitors are of interest as drug leads in neurodegenerative diseases and are currently used in symptomatic treatment of Alzheimer’s disease (AD). In this study, the AChE inhibitory activity of Flustra alkaloids was studied in vitro using the colorimetric method of Ellman and AChE from Electrophorus electricus. Twenty-five compounds isolated from the Icelandic bryozoan F. foliacea were screened at a 100 µM concentration. Two of them, flustramine E and flustramine I, showed inhibition of 48%, and flustramine Q showed 82% inhibition. For flustramine Q, the IC50 was 9.6 µM. Molecular modelling and docking studies indicated that simple in silico designed derivatives of flustramine Q could have potential for increased potency. Marine natural products including brominated indole alkaloids from Flustra foliacea are an interesting new source of AChE inhibitors with potential towards central nervous system disorders, e.g., Alzheimer’s disease.

Natural products as sources of acetylcholinesterase inhibitors: Synthesis, biological activities, and molecular docking studies of osthole-based ester derivatives.

Osthole is a natural coumarin compound which isolated from Cnidium monnieri (L.) Cusson, has extensive pharmacological activities and could be used as a leading compound for drug research and development. In a continuous effort to develop new acetylcholinesterase inhibitors from natural products, eighteen osthole esters were designed, synthesized, and confirmed by 1H NMR, 13C NMR and HRMS. The anti-AChE activity of These derivatives was measured at a concentration of 1.0 mol/mL in vitro by Ellman's method, and the result showed that 4m and 4o had moderate inhibitory activities with 68.8% and 62.6%, respectively. Molecular docking study results further revealed AChE interacted optimally with docking poses 4m and 4o. Network pharmacology also predicted that compound 4m could be involved in Ras signaling pathway, which made it a potential therapeutic target of AD.

Chemical constituents and acetylcholinesterase inhibitory activity of Beilschmiedia insignis Gamble

ABSTRACT. Secondary metabolites from natural products are potential sources of acetylcholinesterase inhibitors, which are key enzymes in the treatment of many neurodegenerative diseases. Inspired by the reported activities of alkaloids herein we report the chemical investigation on the chemical constituents from Beilschmiedia insignis and their acetylcholinesterase inhibitory activity. Isolation of the stem bark of B. insignis led to the isolation and identification of five aporphine alkaloids, namely isocorydine (1), norisocorydine (2), (+)-laurotetanine (3), (+)-N-methyllaurotetanine (4), and (+)-boldine (5), together with β-sitosterol (6), β-sitostenone (7), lupeol (8), and lupenone (9). The chemical structures of these compounds were obtained by analysis of their spectroscopic data, as well as the comparison with that of reported data. Acetylcholinesterase inhibitory activity revealed that all isolated alkaloids were found to inhibit AChE with percentage inhibition values ranged from 44.9 to 74.5%. This is the first report on phytochemicals from B. insignis.
 
 KEY WORDS: Lauraceae, Beilschmiedia insignis, Alkaloid, Acetylcholinesterase, Alzheimer
 
 Bull. Chem. Soc. Ethiop. 2021, 35(3), 685-691.
 DOI: https://dx.doi.org/10.4314/bcse.v35i3.19

Regardless of the Brewing Conditions, Various Types of Tea are a Source of Acetylcholinesterase Inhibitors.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized, among others, by abnormally low levels of the neurotransmitter acetylcholine in the brain. Acetylcholinesterase (AChE) plays a significant role in the process through hydrolysis of the acetylcholine neurotransmitter. Currently, the main method for treatment of AD at a symptomatic stage entails administration of AChE inhibitors to patients diagnosed with the disease. However, it is also possible to take certain steps to treat AD by delivering inhibitors with food. There is a growing body of evidence to suggest that tea (Camellia sinensis) shows numerous beneficial properties, including improving cognitive abilities. This is particularly important in the case of AD patients. The study assessed the impact of brewing conditions on the inhibition of AChE activity observed in tea extracts (black, white, or fruit). Our study revealed that neither temperature nor time of brewing influenced the respective infusions’ ability to inhibit the activity of AChE. Anticholinesterase activity was observed in most of the different types of tea that were analyzed, with the highest rate of inhibition (30.46%–48.54%) evidenced in the Biofix Tea Wild Strawberry brand. The results of our research show that tea may be used as a rich source of cholinesterase inhibitors which play a significant role in AD treatment.

Natural Peptides in Drug Discovery Targeting Acetylcholinesterase.

Acetylcholinesterase-inhibitory peptide has gained much importance since it can inhibit acetylcholinesterase (AChE) and increase the availability of acetylcholine in cholinergic synapses, enhancing cholinergic transmission in pharmacological treatment of Alzheimer’s disease (AD). Natural peptides have received considerable attention as biologically important substances as a source of AChE inhibitors. These natural peptides have high potential pharmaceutical and medicinal values due to their bioactivities as neuroprotective and neurodegenerative treatment activities. These peptides have attracted great interest in the pharmaceutical industries, in order to design potential peptides for use in the prophylactic and therapy purposes. Some natural peptides and their derivatives have high commercial values and have succeeded in reaching the pharmaceutical market. A large number of peptides are already in preclinical and clinical pipelines for treatment of various diseases. This review highlights the recent researches on the various natural peptides and future prospects for AD management.

Effect of some Plants and Pesticides on Acetylcholinesterase

The principal role of acetylcholinesterase (AChE)is the termination of nerve impulse transmission at the cholinergic synapses by rapid hydrolysis of acetylcholine (ACh). Inhibition of AChE serves as a strategy for the treatment of Alzheimer's Disease (AD). Several acetylcholinesterase inhibitors (AChEIs) are used for the symptomatic treatment of AD A potential source of AChE inhibitors is certainly provided by the abundance of plants in nature. The aim of this article is study the effect of some plants and pesticides on acetylcholinesterase. Several plants considered as a source of acetylcholinesterase inhibitors and pesticides special organophosphorus. Cholinesterase inhibitors are the only approved drugs for treating patients with mild to moderately severe Alzheimer's disease, a disorder associated with progressive degeneration of memory and cognitive function. The memory impairment in patients with Alzheimer's disease results from a deficit of cholinergic function in the brain. The most important changes observed in the brain are a decrease in cortical levels of the neurotransmitter acetylcholine and associated enzyme choline transferees. Acetylcholinesterase inhibitors can restore the level of acetylcholine by inhibiting acetylcholinesterase. Principal role of acetyl cholinesterase (AChE) is the termination of nerve impulse transmission at the cholinergic synapses by rapid hydrolysis of acetylcholine (ACh). Inhibition of AChE serves as a strategy for the treatment of Alzheimer's Disease (AD), senile dementia, ataxia, myasthenia gravis and Parkinson's disease (Kumar et al., 2011). There are a few synthetic medicines, e.g., tacrine, donepezil and the natural product-based rivastigmine for treatment of cognitive dysfunction and memory loss associated with AD. There are two types of cholinesterase, AChE and butyrylcholinestrase (BuChE). The AChE is found primarily in the blood and neural synapses. The BuChE is found primarily in the liver. The biggest difference between the two is the substrates. The AChE hydrolyzes acetylcholine (ACh) more quickly and BuChE hydrolyzes butyrylcholine (BuCh) more quickly. The BuCh is a synthetic compound used to distinguish AChE receptors from BuChE receptors. Many of the drugs that are available for treatment of AD target both AChE and BuChE but some are more (Mehta et al., 2012). These compounds have been reported to have their adverse effects including gastrointestinal disturbances and problems associated with bioavailability, which necessitates the interest in finding better AChE inhibitors from natural resources. In traditional practices numerous plants have been used to treat cognitive disorders, including neurodegenerative diseases and different neuron pharmacological disorders.

Chemical constituents and their acetyl cholinesterase inhibitory and antioxidant activities from leaves of Acanthopanax henryi: potential complementary source against Alzheimer’s disease

The aim of this study was to investigate chemical constituents of the leaves of Acanthopanax henryi, and their antioxidant, acetyl cholinesterase inhibitory activities. Caffeoyl quinic acid derivates and flavonoids were obtained from A. henry, through column chromatography technologies, and the content of major constituents was determined by the HPLC-UV method. Anti-oxidant activity of the isolated metabolites was evaluated by free radical scavenging (DPPH, ABTS radicals) and superoxide anion scavenging. The results showed that di-caffeoyl quinic acid derivates had stronger antioxidant activity than positive controls (ascorbic acid, trolox and allopurinol). Acetyl cholinesterase inhibitory activity was estimated on the constituents, among which, quercetin, 4-caffeoyl-quinic acid and 4,5-caffeoyl quinic acid were found to have strong acetyl cholinesterase inhibitory activity with IC50 values ranging from 62.6 to 121.9 μM. The present study showed that some of the tested constituents from the leaves of A. henryi exhibit strong antioxidant and acetyl cholinesterase inhibitory effects. This suggest that the leaves of A. henryi can be used as a new natural complementary source of acetyl cholinesterase inhibitors and anti-oxidant agents, thus being a promising potential complementary source against Alzheimer's disease.

Lycopodiaceae from Panama: A new source of acetylcholinesterase inhibitors

Acetylcholinesterase (AChE) inhibitors have been used for the symptomatic treatment of Alzheimer's disease. Eleven whole plants from Panama belonging to the Lycopodiaceae family have been screened for their anticholinesterase inhibitory and antioxidant activities by a thin-layer chromatography (TLC) bioautography method. Of these, only Lycopodium clavatum subsp. clavatum showed strong AChE inhibition. Seven plant extracts showed moderate inhibition, two of them, Huperzia cf chamaeleon and Huperzia reflexa, also possessed an antioxidant activity. This is the first report of anticholinesterase and antioxidant activities in these two native plants. Additionally, alkaloid extracts of the Lycopodiaceae plants were also analysed by TLC and LC-MS to identify the well-known AchE inhibitor, huperzine A. Two plants, H. cf chamaeleon and H. reflexa var. minor, showed the presence of huperzine.

Screening of plants of Amaryllidaceae and related families from Panama as sources of acetylcholinesterase inhibitors

Context: This is the first comprehensive study of the acetylcholinesterase (AChE) inhibitory activity of species of the family Amaryllidaceae and 13 related families from Panama.Objective: Exploration of the potential sources of AChE inhibitors with radical scavenging activity from Amaryllidaceae and 13 related families from Panama.Materials and methods: The studied plants were screened with anti-acetylcholinesterase bioautographic and DPPH free radical scavenging assays.Results: From the 57 plants studied, eight (14%) showed strong inhibition of AChE, and 29 (51%) plants showed moderate inhibition of AChE.Discussion and conclusion: Sagittaria lancifolia L. (Alismataceae), Crinum jagus (Thomps.) (Amaryllidaceae), Crinum x amabile Donn (Amaryllidaceae), Crinum zeylanicum (L.) L. (Amaryllidaceae), Crocosmia x crocosmiiflora (Lemoine ex Anonymous) N.E. Br. (Iridaceae), Sisyrinchium tinctorium Kunth (Iridaceae), Agapanthus praecox subsp. orientalis (F.M. Leight.) F.M. Leight. (Liliaceae), and Xyris jupicai Rich. (Xyridaceae) were the most active plants, inhibiting AChE at 100 μg on the TLC bioautographic method for the detection of acetylcholinesterase inhibitors. Out of the eight most active plants, two plants, Crinum zeylanicum (L.) L. and Xyris jupicai Rich., showed antioxidant activity.