Abstract
Oxidative stress-mediated neuroinflammatory events are the hallmark of neurodegenerative diseases. The current study aimed to synthesize a series of novel succinamide derivatives and to further investigate the neuroprotective potential of these compounds against scopolamine-induced neuronal injury by in silico, morphological, and biochemical approaches. The characterization of all the succinamide derivatives was carried out spectroscopically via proton NMR (1H-NMR), FTIR and elemental analysis. Further in vivo experiments showed that scopolamine induced neuronal injury, characterized by downregulated glutathione (GSH), glutathione S-transferase (GST), catalase, and upregulated lipid peroxidation (LPO). Moreover, scopolamine increased the expression of inflammatory mediators such as cyclooxygenase2 (COX2), nuclear factor kappa B (NF-kB), tumor necrosis factor (TNF-α), further associated with cognitive impairment. On the other hand, treatment with succinamide derivatives ameliorated the biochemical and immunohistochemical alterations induced by scopolamine, further supported by the results obtained from molecular docking and binding affinities.
Highlights
Consistent reports have reiterated the involvement of inflammatory cascade and oxidative stress in the pathophysiology of neurodegenerative disorders including Alzheimer’s disease (AD), ischemic stroke, and Parkinson’s disease [1]
Along with glutamate-induced excitotoxicity and inflammatory factors, the vicious cycles induced by reactive oxygen species (ROS) eventually activate the injury pathways and lead to cell necrosis and apoptosis [10]
Melting points of all newly synthesized succinamide derivatives were recorded via the Digital Gallen Kamp apparatus (Sanyo, Osaka, Japan)
Summary
Consistent reports have reiterated the involvement of inflammatory cascade and oxidative stress in the pathophysiology of neurodegenerative disorders including Alzheimer’s disease (AD), ischemic stroke, and Parkinson’s disease [1]. ROS damage lipids, proteins and DNA, and cause intracellular organelle destruction via plasma and organelle membrane peroxidation [9]. These could further stimulate the release of biologically active free fatty acids, such as arachidonic acid and DNA fragmentation. Along with glutamate-induced excitotoxicity and inflammatory factors, the vicious cycles induced by ROS eventually activate the injury pathways and lead to cell necrosis and apoptosis [10]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call