Document Type
Article
Source of Publication
Journal of Inflammation Research
Publication Date
1-1-2022
Abstract
Objective: The study investigated the effect of newly synthesized benzimidazole derivatives against ethanol-induced neurodegenera-tion. According to evidence, ethanol consumption may cause a severe insult to the central nervous system (CNS), resulting in mental retardation, neuronal degeneration, and oxidative stress. Targeting neuroinflammation and oxidative stress may be a useful strategy for preventing ethanol-induced neurodegeneration. Methodology: Firstly, the newly synthesized compounds were subjected to molecular simulation and docking in order to predict ligand binding status. Later, for in vivo observations, adult male Sprague Dawley rats were used for studying behavioral and oxidative stress markers. ELIZA kits were used to analyse tumour necrosis factor-alpha (TNF-), nuclear factor-B (NF-B), interleukin (IL-18), and pyrin domain-containing protein 3 (NLRP3) expression, while Western blotting was used to measure IL-1 and Caspase-1 expression. Results: Our findings suggested that altered levels of antioxidant enzymes were associated with elevated levels of TNF-α, NF-B, IL-1, IL-18, Caspase-1, and NLRP3 in the ethanol-treated group. Furthermore, ethanol also caused memory impairment in rats, as measured by behavioural tests. Pretreatment using selected benzimidazole significantly increased the combat of the brain against ethanol-induced oxidative stress. The neuroprotective effects of benzimidazole derivatives were promoted by their free radical scavenging activity, augmentation of endogenous antioxidant proteins (GST, GSH), and amelioration of lipid peroxide (LPO) and other pro-inflammatory mediators. Molecular docking and molecular simulation studies further supported our hypothesis that the synthetic compounds Ca and Cb had an excellent binding affinity with proper bond formation with their targets (TNF-α and NLRP3). Conclusion: It is revealed that these benzimidazole derivatives can reduce ethanol-induced neuronal toxicity by regulating the expression of cytokines, antioxidant enzymes, and the inflammatory cascade.
DOI Link
ISSN
Publisher
Informa UK Limited
Volume
15
First Page
3873
Last Page
3890
Disciplines
Medicine and Health Sciences
Keywords
benzimidazole derivatives, ethanol, neurodegeneration, neuroinflammation, NLRP3 inhibition, oxidative stress
Scopus ID
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Ullah, Aman; Al Kury, Lina Tariq; Althobaiti, Yusuf S.; Ali, Tahir; and Shah, Fawad Ali, "Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment" (2022). All Works. 5258.
https://zuscholars.zu.ac.ae/works/5258
Indexed in Scopus
yes
Open Access
yes
Open Access Type
Gold: This publication is openly available in an open access journal/series