Abstract:
: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 Aβ1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ1-42 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 Aβ1-42 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 Aβ1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.
journal_name
Hum Exp Toxicoljournal_title
Human & experimental toxicologyauthors
Husain I,Akhtar M,Abdin MZ,Islamuddin M,Shaharyar M,Najmi AKdoi
10.1177/0960327117705431subject
Has Abstractpub_date
2018-04-01 00:00:00pages
399-411issue
4eissn
0960-3271issn
1477-0903journal_volume
37pub_type
杂志文章abstract::Cyanate and its active form isocyanate are formed mainly in the process of nonenzymatic urea biodegradation. Cyanate is capable of protein S- and N-carbamoylation, which can affect their activity. The present studies aimed to demonstrate the effect of cyanate on activity of the enzymes implicated in anaerobic cysteine...
journal_title:Human & experimental toxicology
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journal_title:Human & experimental toxicology
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pub_type: 临床试验,杂志文章
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