Phosphodiesterase (PDE) III inhibitor, Cilostazol, improved memory impairment in aluminum chloride-treated rats: modulation of cAMP/CREB pathway

Autor: Mona Khalifa, Rania M. Abdelsalam, Marwa M. Safar, Hala F. Zaki
Rok vydání: 2022
Předmět:
Zdroj: Inflammopharmacology. 30:2477-2488
ISSN: 1568-5608
0925-4692
DOI: 10.1007/s10787-022-01010-1
Popis: The most prevalent type of dementia is Alzheimer's disease (AD), which is currently incurable. Existing treatments for Alzheimer's disease, such as acetylcholinesterase inhibitors, are only effective for symptom relief. Disease-modifying medications for Alzheimer's disease are desperately required, given the enormous burdens that the disease places on individuals and communities. Phosphodiesterase (PDE) inhibitors are gaining a lot of attention in the research community because of their potential in treating age-related cognitive decline. Cilostazol is a selective PDE III inhibitor used as antiplatelet agent through cAMP response element-binding (CREB) protein phosphorylation pathway (cAMP/CREB). The neuroprotective effect of cilostazol in AD-like cognitive decline in rats was investigated in this study. After 2 months of intraperitoneal administration of 10 mg/kg aluminum chloride, Morris water maze and Y-maze (behavioral tests) were performed. After that, histological and biochemical examinations of the hippocampal region were carried out. Aluminum chloride-treated rats showed histological, biochemical, and behavioral changes similar to Alzheimer's disease. Cilostazol improved rats' behavioral and histological conditions, raised neprilysin level while reduced levels of amyloid-beta protein and phosphorylated tau protein. It also decreased the hippocampal levels of tumor necrosis factor-alpha, nuclear factor-kappa B, FAS ligand, acetylcholinesterase content, and malondialdehyde. These outcomes demonstrate the protective activity of cilostazol versus aluminum-induced memory impairment.
Databáze: OpenAIRE
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