Recent attention is focused on the impact of diet on health and mental well-being. High-salt and cholesterol diet (HSCD) is known to be associated with neuroinflammation which is the predominant factor for neurodegenerative disease like Alzheimer disease (AD). In the present study, we examined the neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated that HSCD-induced cognitive impairment as determined by Morris water maze (MWM) task. HSCD also activated nuclear factor kappaB (NF-kB) signaling pathway. The cytokine response was measured using a cytometric bead-based assay quantified by flow cytometry. Treatment with rosuvastatin decreased the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and increased interleukin-10 (IL-10) in a dose-dependent manner. Our results also demonstrated that the rosuvastatin modulates neuronal cell death by inhibiting the overexpression of NF-kB in the CA1 region of hippocampus. In addition, molecular docking study of rosuvastatin indicated high affinity and tighter binding capacity for the active site of the NF-kB. These results suggest that HSCD-triggered inflammatory response and cognitive impairment may be associated with NF-κB signaling pathway. Therefore, treatment with rosuvastatin could be a potential new therapeutic strategy for sporadic dementia of AD.
Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aβ peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aβ peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.