scholarly journals Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1090 ◽  
Author(s):  
Edward J. Okello ◽  
Joshua Mather
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Green Tea ◽  
Competitive Inhibition ◽  
Cholinergic Neurons ◽  
Cholinesterase Inhibition ◽  
Optimal Method ◽  
Butyryl Cholinesterase ◽  
Kinetics Of

Alzheimer’s disease (AD) is characterised by the apoptosis of cholinergic neurons and the consequent attenuation of acetylcholine mediated neurotransmission, resulting in neurodegeneration. Acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE) are attractive therapeutic targets in the treatment of AD since inhibition of these enzymes can be used to restore synaptic concentrations of acetylcholine. Whilst inhibitors for these enzymes such as galantamine and rivastigmine have been approved for use, none are able to halt the progression of AD and are responsible for the production of troublesome side-effects. Efficacious cholinesterase inhibitors have been isolated from natural plant-based compounds with many demonstrating additional benefits beyond cholinesterase inhibition, such as antioxidation and anti-inflammation, which are key parts of AD pathology. In this study, five natural flavan-3-ol (catechin) compounds: ((-)-epicatechin (EC), catechin, (-)-epicatechin-3-gallate (ECG),) (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), isolated from green tea, were screened for their cholinesterase inhibitory activity using the Ellman assay. The kinetics of inhibition was determined using reciprocal Lineweaver-Burk plots. EGCG was the only compound found to produce statistically significant, competitive inhibition, of both AChE (p < 0.01) and BuChE (p < 0.01) with IC50 values of 0.0148 µmol/mL and 0.0251 µmol/mL respectively. These results, combined with previously identified antioxidative and anti-inflammatory properties, highlight the potential use of EGCG in the treatment of AD, provided it can be delivered to cholinergic neurons in therapeutic concentrations. Further testing of EGCG in vivo is recommended to fully characterise the pharmacokinetic properties, optimal method of administration and efficacy of this novel plant-based compound.

scholarly journals Atrophy of Basal Forebrain Initiates with Tau Pathology in Individuals at Risk for Alzheimer’s Disease

2019 ◽  
Vol 30 (4) ◽  
pp. 2083-2098
Author(s):  
Jose L Cantero ◽  
Mercedes Atienza ◽  
Carmen Lage ◽  
Laszlo Zaborszky ◽  
Eduard Vilaplana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Basal Forebrain ◽  
Cholinergic Neurons ◽  
Nucleus Basalis ◽  
Tau Pathology ◽  
Projection System ◽  
Prodromal Ad

Abstract Evidence suggests that the basal forebrain (BF) cholinergic system degenerates early in the course of Alzheimer’s disease (AD), likely due to the vulnerability of BF cholinergic neurons to tau pathology. However, it remains unclear whether the presence of tauopathy is the only requirement for initiating the BF degeneration in asymptomatic subjects at risk for AD (AR-AD), and how BF structural deficits evolve from normal aging to preclinical and prodromal AD. Here, we provide human in vivo magnetic resonance imaging evidence supporting that abnormal cerebrospinal fluid levels of phosphorylated tau (T+) are selectively associated with bilateral volume loss of the nucleus basalis of Meynert (nbM, Ch4) in AR-AD individuals. Spreading of atrophy to medial septum and vertical limb of diagonal band Broca (Ch1–Ch2) occurred in both preclinical and prodromal AD. With the exception of A+, all groups revealed significant correlations between volume reduction of BF cholinergic compartments and atrophy of their innervated regions. Overall, these results support the central role played by tauopathy in instigating the nbM degeneration in AR-AD individuals and the necessary coexistence of both AD proteinopathies for spreading damage to larger BF territories, thus affecting the core of the BF cholinergic projection system.

Botanical Sources for Alzheimer’s: A Review on Reports From Traditional Persian Medicine

2017 ◽  
Vol 32 (7) ◽  
pp. 429-437 ◽  
Author(s):  
Ayda Hosseinkhani ◽  
Ali Sahragard ◽  
Aida Namdari ◽  
Mohammad M. Zarshenas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medicinal Plants ◽  
Herbal Medicines ◽  
Mechanisms Of Action ◽  
Cholinesterase Inhibition ◽  
Clinical Validation ◽  
Persian Medicine ◽  
Traditional Persian Medicine ◽  
Butyryl Cholinesterase

Herbal medicines for the treatment of Alzheimer’s disease (AD) have attracted considerable attention nowadays. Alzheimer’s disease is described in traditional Persian medicine (TPM) by the term Nesyān. In this study, 5 main medicinal medieval Persian manuscripts were reviewed to filter plants reported for the treatment of Nesyān. Databases were searched for related possible mechanisms of action of these medicinal plants. Each herb was searched for along with these keywords: “acetyl and butyryl cholinesterase inhibition,” “antioxidant,” “anti-inflammatory,” and “anti-amyloidogenic.” In Total, 44 herbs were used for the treatment of Nesyān; 40 of those were authenticated. Also, 30 plants had at least one of the mechanisms of action that were searched for or related pharmacological functions known for the treatment of AD. In this work, we introduce promising candidates in TPM that could undergo further investigation for identification of their active compounds and clinical validation in the treatment of AD.

scholarly journals Diplazium esculentum (Retz.) Sw. reduces BACE-1 activities and amyloid peptides accumulation in Drosophila models of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanit Kunkeaw ◽  
Uthaiwan Suttisansanee ◽  
Dunyaporn Trachootham ◽  
Jirarat Karinchai ◽  
Boonrat Chantong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Complex Disease ◽  
Cholinergic Neurons ◽  
Ethanolic Extract ◽  
Edible Plant ◽  
Bace 1

AbstractAlzheimer’s disease (AD), one type of dementia, is a complex disease affecting people globally with limited drug treatment. Thus, natural products are currently of interest as promising candidates because of their cost-effectiveness and multi-target abilities. Diplazium esculentum (Retz.) Sw., an edible fern, inhibited acetylcholinesterase in vitro, inferring that it might be a promising candidate for AD treatment by supporting cholinergic neurons. However, evidence demonstrating anti-AD properties of this edible plant via inhibiting of neurotoxic peptides production, amyloid beta (Aβ), both in vitro and in vivo is lacking. Thus, the anti-AD properties of D. esculentum extract both in vitro and in Drosophila models of Aβ-mediated toxicity were elucidated. Findings showed that an ethanolic extract exhibited high phenolics and flavonoids, contributing to antioxidant and inhibitory activities against AD-related enzymes. Notably, the extract acted as a BACE-1 blocker and reduced amyloid beta 42 (Aβ42) peptides in Drosophila models, resulting in improved locomotor behaviors. Information gained from this study suggested that D. esculentum showed potential for AD amelioration and prevention. Further investigations in vertebrates or humans are required to determine the effective doses of D. esculentum against AD, particularly via amyloidogenic pathway.

Design, Synthesis and Biological Evaluation of New Cycloalkyl Fused Quinolines Tethered to Isatin Schiff Bases as Cholinesterase Inhibitors

2020 ◽  
Vol 23 ◽  
Author(s):  
Baswaraju Macha ◽  
Ravindra Kulkarni ◽  
Anil Kumar Garige ◽  
Rambabu Palabindala ◽  
Raghuramrao Akkinepally ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Schiff Bases ◽  
Active Site ◽  
Inhibitory Activity ◽  
Docking Studies ◽  
Behavioral Studies ◽  
Cholinesterase Inhibitory Activity ◽  
Butyryl Cholinesterase

Aims and Objective: Alzheimer’s disease is now a most prevalent neuro degenerative disease of central nervous system leading to dementia in elderly aged population. Numerous pathological changes have been associated in the progression of Alzheimer’s disease. One of such pathological hypothesis is declined cholinergic activity which eventually affects cognitive and memory deficits. Inhibition cholinesterases will apparently elevate acetyl choline levels which is benefactor on cognitive symptoms of the disease. This manuscript describes the new tacrine derivatives tethered to isatin Schiff bases through alkanoyl linker and screened for cholinesterase inhibitory activity. Materials and Methods: Tacrine and two more cycloalkyl ring fused quinolones were synthesized and converted to Ncycloalkyl fused quinoline chloroamides. Isatin Schiff bases were also synthesized by the reaction between isatin and substituted aromatic anilines and in subsequent reaction, isatin Schiff bases were reacted with cycloalkyl fused quinolones to afford anticipated compounds 10a-i, 11a-i and 12a-i. All the compounds have been screened for acetyl and butyryl cholinesterase inhibitory activity and in vivo behavioral studies. Binding interactions of the desired compounds have also been studied by docking them in active site of both cholinesterases. Results: Three compounds 12d, 12e and 12h with propionyl and butyroyl linker between amine and isatin Schiff base scaffold have shown potent acetyl and butyryl cholinesterase inhibitory activity. However most potent cholinesterase inhibitor was 13d with IC50 value of 0.71±0.004 and 1.08±0.02 μM against acetyl and butyryl cholinesterases respectively. The hepatotoxicity of potent compounds revealed that the tested compounds were less hepatotoxic than tacrine and also exhibited encouraging in vivo behavioral studies in test animals. Docking studies of all the molecules disclosed close hydrogen bond interactions within the binding site of both cholinesterases. Conclusion: New cycloalkyl fused quinolones tethered with alkoyl linker to isatin Schiff bases endowed significant and potent cholinesterase inhibitory activities. Few of the compounds have also exhibited lesser hepatotoxicity and all the synthesized compounds were good in behavioral studies. Molecular docking studies also indicated close interactions in active site of cholinesterases.

Natural Anti-inflammatory compounds as Drug candidates in Alzheimer’s disease

2020 ◽  
Vol 27 ◽  
Author(s):  
Reyaz Hassan Mir ◽  
Abdul Jalil Shah ◽  
Roohi Mohi-ud-din ◽  
Faheem Hyder Potoo ◽  
Mohd. Akbar Dar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Protective Action ◽  
New Drugs ◽  
Huperzine A ◽  
Brain Disorder ◽  
Anti Inflammatory

: Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. So to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol were reported molecules for the treatment of AD. Several alkaloids such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.

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