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.
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Experiments were performed following the ethical standards according to the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (Institute of Laboratory Animal Resources 1996) in Faculty of Medicine, Alexandria University, Egypt.
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This research is supported by a core grant from Science and Technology Development Fund (STDF) in Egypt with grant number 4479.
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Hafez, H.S., Ghareeb, D.A., Saleh, S.R. et al. Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats. Psychopharmacology 234, 3037–3053 (2017). https://doi.org/10.1007/s00213-017-4690-x
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DOI: https://doi.org/10.1007/s00213-017-4690-x