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- Volume 20, Issue 3, 2024
Current Enzyme Inhibition - Volume 20, Issue 3, 2024
Volume 20, Issue 3, 2024
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New Aspects in the Mechanism of Action of 3-hydroxy-3-methylglutaryl-COA Reductase (HMG-CoA reductase): Cyclic Lactones - Potential Inhibitors of the Enzyme (Review)
Authors: D.I. Boyarintsev, I.V. Kuzminov and M.V. OrlovaThe aim is to systematize data from literature sources on the study of changes in the activity of HMGR enzymes and lipid metabolism under the influence of cyclic lactones, identify among them new potential inhibitors of HMGR and formulate hypotheses about the details of the mechanism of action of the enzyme in relation to the product - mevalonolactone.
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The Transformative Potential of Oxidoreductases in Pollutant Remediation – A Review
Authors: Asia Khalil, Ayman Iqbal, Muhammad Aqib Shabir, Ammarah Hasnain and Zainab NiazIn this modern era, the environment is being contaminated with toxic pollutants as a result of anthropogenic activities. To overcome the harmful effects of pollutants, scientists have developed ideas and technologies. Biotechnology provides a green approach for decontaminating the environment, i.e., bioremediation. Several organisms have been explored for their enzymes. Enzymes belonging to various classes are useful for degrading, transforming, or removal of pollutants. Oxidoreductases produced by different plants, bacteria, and fungi are useful for deterioration of toxic pollutants, like compounds having aroma, called aromatic compounds (benzene, chlorine, phenols, phenanthrene, etc.), PAHs (Polyaromatic Hydrocarbons), various dyes, etc. Oxidoreductases are further classified as laccases, peroxidases, and oxygenases. All three classes have proven to be efficacious in the field of bioremediation. Microorganism strains have also been genetically engineered for the production of enzymes. Oxidoreductases can be used to remove pollutants from industrial waste. This review has classified all the species that produce oxidoreductase enzymes, their mechanism of action, and the pollutants that have been removed by using oxidoreductases.
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Apocynaceae as a Potential Source for Acetylcholinesterase Inhibition in Symptomatic Regulation and Management of Alzheimer's Disease
Authors: Priyanka Kumari, Naveen Sarwa, Deepak Meena, Ajaya Eesha and Navneet Singh ChaudharyMemory 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.
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In silico, In vitro, and In vivo Evaluation of the Anti-alzheimer’s Activity of Berberine
BackgroundAlzheimer’s disease (AD), a progressive neurodegenerative disease for which there is no effective cure is among the leading causes of death worldwide.
ObjectivesTo investigate the potential anti-AD activity of berberine (BBR).
MethodsIn silico assessment included molecular docking and ADMET prediction. BBR’s in vitro inhibitory activity of the target selected from docking results was assessed via colorimetric inhibitor screening assay. BBR’s LC50 in adult zebrafish was determined via an Acute Toxicity Study. ZnCl2 concentration for AD induction was determined via toxicity study and T-maze test. Finally, zebrafish were treated with ZnCl2 alone or simultaneously with either BBR or donepezil and assessed via the inhibitory avoidance task, followed by ELISA of AD-related biomarker levels in brain tissue.
ResultsThe in silico assessment showed BBR’s desirable drug properties and binding affinity on selected AD-related targets, which was the greatest docking score with AChE. The in vitro IC50 on AChE was 3.45 μM. The LC50 in adult zebrafish was calculated at 366 ppm. In the T-maze test, ZnCl2 at 2.5 ppm caused the greatest cognitive impairment accompanied by moderate freezing. In the inhibitory avoidance test, fish treated with either 100 ppm BBR or 2.5 ppm donepezil had significantly better performance than ZnCl2-treated fish. ZnCl2-treated zebrafish brain tissue had the highest Aβ levels and AChE activity of all groups, but these were significantly lower in donepezil- and BBR-treated fish. ZnCl2- and donepezil-treated fish had similar TNF-α levels, whereas BBR treatment significantly lowered them close to those of untreated fish.
ConclusionBBR showed anti-amyloidogenic, anti-AChE, and anti-inflammatory effects, which support its potential use in AD therapy.
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Volumes & issues
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Volume 20 (2024)
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Volume 19 (2023)
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Volume 18 (2022)
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Volume 17 (2021)
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Volume 16 (2020)
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Volume 15 (2019)
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Volume 14 (2018)
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Volume 13 (2017)
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Volume 12 (2016)
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Volume 11 (2015)
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Volume 10 (2014)
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Volume 9 (2013)
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Volume 8 (2012)
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Volume 7 (2011)
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Volume 6 (2010)
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Volume 5 (2009)
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Volume 4 (2008)
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Volume 3 (2007)
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Volume 2 (2006)
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Volume 1 (2005)