Title
Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats
Document Type
Article
Abstract
Background: Alzheimer’s disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors. Objective: The present study aimed to evaluate the possible enhancing effects of IPRI on memory impairments caused by scopolamine administration. Methods: Male rats were administered IPRI (50 mg/kg, oral) 2 h before scopolamine injection (2 mg/kg, intraperitoneally injected) daily for 4 weeks. Effects of IPRI on acetylcholinesterase activity, amyloid-β precursor processing, and neuroplasticity in the rats’ hippocampus were investigated. Results: Daily administration of IPRI reverted memory impairment caused by scopolamine as measured by the reduction of the escape latency. IPRI significantly alleviated the oxidative stress and restored the mRNA expression of both cAMP-response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Furthermore, it significantly increased the expression of ADAM10 and ADAM17 (two putative α-secretase enzymes) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) that associated with decreased expression of β-secretase (BACE) in the hippocampus. Finally, both the amyloid-β (Aβ) and Tau pathologies were reduced. Conclusions: IPRI showed promising neuroprotective effects against scopolamine-induced memory dysfunction in rats. These findings contributed to the stimulation of α-secretase enzymes, the activation of MAPK/ERK1/2, and the alleviation of oxidative stress.
Publication Date
10-1-2017
Faculty
Faculty of Applied Health Sciences Technology
Subject Area
Life Sciences, Pharmacology, Toxicology, Pharmaceutical Science
Indexed in Scopus
yes
Indexed in Web Of Science
yes
DOI
https://doi.org/10.1007/s00213-017-4690-x
Volume
234
Keywords
Acetylcholinesterase, Alzheimer’s disease, Amyloid-β, MAPK/ERK1/2 pathway, Neuroprotection
ISSN
00333158
eISSN
14322072
Recommended Citation
Hafez, Hani S.; Ghareeb, Doaa A.; Saleh, Samar R.; Abady, Mariam M.; El Demellawy, Maha A.; Hussien, Hend; and Abdel-Monem, Nihad, "Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats" (2017). Faculty of Applied Health Sciences Technology. 99.
https://pks.pua.edu.eg/applied_health_publications/99