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Cited 42 time in webofscience Cited 46 time in scopus
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NF-kappa B Inhibitors Attenuate MCAO Induced Neurodegeneration and Oxidative Stress-A Reprofiling Approachopen access

Authors
Ali, AwaisShah, Fawad AliZeb, AlamMalik, ImranAlvi, Arooj MohsinAlkury, Lina TariqRashid, SajidHussain, IhtiaqUllah, NajeebKhan, Arif UllahKoh, Phil OkLi, Shupeng
Issue Date
24-Mar-2020
Publisher
FRONTIERS MEDIA SA
Keywords
reprofiling; MCAO stroke; p-NF-kappa B; atorvastatin; cephalexin; mycophenolate; caeffic acid phenethyl ester
Citation
FRONTIERS IN MOLECULAR NEUROSCIENCE, v.13
Indexed
SCIE
SCOPUS
Journal Title
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume
13
URI
https://scholarworks.gnu.ac.kr/handle/sw.gnu/6812
DOI
10.3389/fnmol.2020.00033
ISSN
1662-5099
Abstract
Stroke is the leading cause of morbidity and mortality worldwide. About 87% of stroke cases are ischemic, which disrupt the physiological activity of the brain, thus leading to a series of complex pathophysiological events. Despite decades of research on neuroprotectants to probe for suitable therapies against ischemic stroke, no successful results have been obtained, and new alternative approaches are urgently required in order to combat this pathological torment. To address these problems, drug repositioning/reprofiling is explored extensively. Drug repurposing aims to identify new uses for already established drugs, and this makes it an attractive commercial strategy. Nuclear factor-kappa beta (NF-kappa B) is reported to be involved in many physiological and pathological conditions, such as neurodegeneration, neuroinflammation, and ischemia/reperfusion (I/R) injury. In this study, we examined the neuroprotective effects of atorvastatin, cephalexin, and mycophenolate against the NF-kappa B in ischemic stroke, as compared to the standard NF-kappa B inhibitor caeffic acid phenethyl ester (CAPE). An in-silico docking analysis was performed and their potential neuroprotective activities in the in vivo transient middle cerebral artery occlusion (t-MCAO) rat model was examined. The percent (%) infarct area and 28-point composite neuro score were examined, and an immunohistochemical analysis (IHC) and enzyme-linked immunosorbent assay (ELISA) were further performed to validate the neuroprotective role of these compounds in stroke as well as their potential as antioxidants. Our results demonstrated that these novels NF-kappa B inhibitors could attenuate ischemic stroke-induced neuronal toxicity by targeting NF-kappa B, a potential therapeutic approach in ischemic stroke.
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