10.3389/fnmol.2020.00033.s001 Awais Ali Awais Ali Fawad Ali Shah Fawad Ali Shah Alam Zeb Alam Zeb Imran Malik Imran Malik Arooj Mohsin Alvi Arooj Mohsin Alvi Lina Tariq Alkury Lina Tariq Alkury Sajid Rashid Sajid Rashid Ishtiaq Hussain Ishtiaq Hussain Najeb Ullah Najeb Ullah Arif Ullah Khan Arif Ullah Khan Phil Ok Koh Phil Ok Koh Shupeng Li Shupeng Li Presentation_1_NF-κB Inhibitors Attenuate MCAO Induced Neurodegeneration and Oxidative Stress—A Reprofiling Approach.PPTX Frontiers 2020 reprofiling MCAO stroke p-NF-κB atorvastatin cephalexin mycophenolate caeffic acid phenethyl ester 2020-03-26 14:41:16 Presentation https://frontiersin.figshare.com/articles/presentation/Presentation_1_NF-_B_Inhibitors_Attenuate_MCAO_Induced_Neurodegeneration_and_Oxidative_Stress_A_Reprofiling_Approach_PPTX/12034524 <p>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-κB) 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-κB in ischemic stroke, as compared to the standard NF-κB 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-κB inhibitors could attenuate ischemic stroke-induced neuronal toxicity by targeting NF-κB, a potential therapeutic approach in ischemic stroke.</p>