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

Abstract

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.

Neuromodulatory effect of vardenafil on aluminium chloride/d-galactose induced Alzheimer’s disease in rats: emphasis on amyloid-beta, p-tau, PI3K/Akt/p53 pathway, endoplasmic reticulum stress, and cellular senescence

“…Contradictorily, co-treatment with VAR high dose restored nearly the original neuronal architecture and mitigated the number of degenerated neurons while the VAR low dose mildly alleviated the AlCl 3 / d -gal-induced neurodegeneration. Interestingly, these results were supported by an earlier study proved that cilostazol, PDE-3 inhibitor, abrogated the histological anomalies in AD rat model (Khalifa et al 2022 ).…”