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Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer’s disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress
Ebtsam S Abdel-Lah, Hoda S. Sherkawy, Wafaa H. Mohamed, Mariam A. Fawy, Asmaa A. Hasan, Asmaa A. Muhammed, Amira F. Taha, Abeer A. Tony et al.. Inflammopharmacology, 2025-05-05
Topic: Brain proteins, microglia and lab models
One of the major consequences of diabetes mellitus that has gained attention due to its rising incidence is cognitive impairment. 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 combination 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 impairments associated with neurodegenerative disorders.
Key findings
- 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.
- 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 impairments associated with neurodegenerative disorders.
Why it matters
In a rat model, empagliflozin combined with memantine improved cognitive performance and changed markers of neuroinflammation and oxidative stress. This is animal research, so it does not show that this drug combination treats or prevents Alzheimer's disease in humans.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 37 of the 96 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Inflammopharmacology) |
| Journal's citation record | 1 / 4 | Inflammopharmacology: journal h-index 92 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “rats”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 11 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 6.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Marwa G. Gamea holds only 5 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | Assiut University: institution h-index 253 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40325262) |
| Free to read | 2 / 2 | Free to read |
| Points | 37 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 37 of the 96 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s10787-025-01755-5
- PubMed: 40325262
- Original source →
- Free full text: Inflammopharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Abdel-Lah, E. S., Sherkawy, H. S., Mohamed, W. H., Fawy, M. A., Hasan, A. A., Muhammed, A. A., et al. (2025). Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer’s disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress. Inflammopharmacology. https://doi.org/10.1007/s10787-025-01755-5
Vancouver
Abdel-Lah ES, Sherkawy HS, Mohamed WH, Fawy MA, Hasan AA, Muhammed AA, et al. Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer’s disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress. Inflammopharmacology. 2025. doi:10.1007/s10787-025-01755-5. PMID: 40325262.
BibTeX
@article{abdellah2025-40325262,
author = {Abdel-Lah, Ebtsam S and Sherkawy, Hoda S. and Mohamed, Wafaa H. and Fawy, Mariam A. and Hasan, Asmaa A. and Muhammed, Asmaa A. and Taha, Amira F. and Tony, Abeer A. and others},
title = {{Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer’s disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress}},
journal = {Inflammopharmacology},
year = {2025},
doi = {10.1007/s10787-025-01755-5},
pmid = {40325262},
url = {https://doi.org/10.1007/s10787-025-01755-5}
}
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