تاريخ البحث
قسم البحث
مجلة البحث
Inflammopharmacology
الناشر
springer
تصنيف البحث
Q1
عدد البحث
33
موقع البحث
https://doi.org/10.1007/s10787-025-01755-5
سنة البحث
2025
المشارك في البحث
ملخص البحث
One of the major consequences of diabetes mellitus that has gained attention due to its rising incidence is cognitive impair�
ment. Recent research suggested that sodium-glucose cotransporter-2 (SGLT-2) inhibitors can mitigate memory impairment
linked to Alzheimer’s disease and are now being explored for their cognitive benefits. However, their mechanisms were not
thoroughly studied. This research investigates the hypothesis of the neuroprotective effect of empagliflozin administration
against scopolamine-heavy metal mixture (SCO+HMM)-treated Alzheimer’s rat models in comparison with memantine as a
reference drug and the impact of their combination. Yet, the neuroprotective effects of memantine and empagliflozin combina�
tion against cognitive impairment have not been previously explored. This study employed adult male albino rats categorized
into five groups. The impact of empagliflozin, memantine, and their concomitant administration on cognitive performance
was assessed in a scopolamine and heavy metal mixture-treated Alzheimer’s disease model in rats. The assessment of rats’
cognitive behavior, memory, and spatial learning was conducted, followed by an evaluation of hippocampal brain-derived
neurotrophic factor (BDNF), beta-secretase (BACE-1), oxidative stress (OS), and inflammatory marker activity. And, a
western blot analysis was conducted to detect phosphorylated 5’ AMP-activated protein kinase (p-AMPK), phosphorylated
mammalian target of rapamycin (p-mTOR), and heme oxygenase-1 (HO-1). Hippocampal and cerebellar histopathology were
thoroughly examined, in addition to the expressions of amyloid β (Aβ). The current data demonstrate the involvement of the
pAMPK/mTOR/HO-1 signaling pathway in empagliflozin neuroprotection against SCO+HMM-induced AD. In addition,
it reduces AD hallmarks (Aβ and BACE1), neuro-inflammation, and oxidative stress sequelae, and enhances neurogenesis
and synaptic density via BDNF. This study proposes that EMPA, especially when co-administered with other conventional
anti-Alzheimer therapy, may be formulated into an innovative therapeutic strategy for the enhancement of cognitive impair�
ments associated with neurodegenerative disorders.