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Paeoniflorin exercise-mimetic potential regulates the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways to reduce cognitive impairments and neuroinflammation in amnesic mouse model
Jae-Won Choi, Joo Young Im, Rengasamy Balakrishnan. Biomedicine & Pharmacotherapy, 2025-07-01
Topic: Brain proteins, microglia and lab models
Microglia-mediated neuroinflammation plays a crucial role in memory and cognitive deficits and the development of early mild cognitive impairment (MCI) associated with Alzheimer's disease (AD). Paeoniflorin (PF) has been established as an effective antioxidant and anti-apoptotic agent. This study investigated the protective effects of PF on neuroinflammation, amyloidogenesis, and memory impairments in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and a C57BL/6 J amnesic mouse model. In BV-2 microglial cells, PF treatment inhibited LPS-stimulated nitric oxide (NO) production, attenuated microglial overactivation, and suppressed the excessive release of inflammatory mediators (iNOS and COX-2) in a concentration-dependent manner. More crucially, PF regulated the LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs)-including p38, ERK, and JNK-while also suppressing NF-κB nuclear transport and inhibiting IκB-α phosphorylation. In the in vivo study, PF (10 or 20 mg/kg) treatment significantly improved spatial learning memory and cognitive function and ameliorated memory deficits. Furthermore, PF administration upregulated BDNF, p-CREB, Nrf2, and HO-1 expression, which are biomarkers of neuroprotective and antioxidant effects. This was accompanied by a reduction in markers of neuroinflammation (iNOS and COX-2), the inhibition of microglia and astrocytes overactivation, and decreased expression of amyloidogenic protein markers APP and BACE-1 in the hippocampus and cerebral cortex. Further, PF inhibited the LPS-promoted phosphorylation of MAPK signaling, thereby reducing the phosphorylation level of IκB-α and inhibiting NF-κB activation in the hippocampus and cerebral cortex. Our results suggest that PF confers neuroprotective effects in an LPS model of Alzheimer-associated MCI by regulating the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways.
Key findings
- Microglia-mediated neuroinflammation plays a crucial role in memory and cognitive deficits and the development of early mild cognitive impairment (MCI) associated with Alzheimer's disease (AD).
- In the in vivo study, PF (10 or 20 mg/kg) treatment significantly improved spatial learning memory and cognitive function and ameliorated memory deficits.
- Our results suggest that PF confers neuroprotective effects in an LPS model of Alzheimer-associated MCI by regulating the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways.
Why it matters
In a mouse model of memory impairment and in microglial cells, paeoniflorin improved learning and memory and reduced inflammation and amyloid-related markers. These are animal and cell findings, and it is not established whether the compound would benefit people with Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 42/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biomedicine & Pharmacotherapy) |
| Journal's citation record | 2 / 4 | Biomedicine & Pharmacotherapy: journal h-index 227 (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 “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 16 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.9× 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 | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Rengasamy Balakrishnan: h-index 21 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Florida: institution h-index 1,303 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40592207) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.biopha.2025.118299
- PubMed: 40592207
- Original source →
- Free full text: Biomedicine & Pharmacotherapy →
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. Check the citation against the original before you use it.
APA 7th
Choi, J.-W., Im, J. Y., & Balakrishnan, R. (2025). Paeoniflorin exercise-mimetic potential regulates the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways to reduce cognitive impairments and neuroinflammation in amnesic mouse model. Biomedicine & Pharmacotherapy. https://doi.org/10.1016/j.biopha.2025.118299
Vancouver
Choi J.-W, Im JY, Balakrishnan R. Paeoniflorin exercise-mimetic potential regulates the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways to reduce cognitive impairments and neuroinflammation in amnesic mouse model. Biomedicine & Pharmacotherapy. 2025. doi:10.1016/j.biopha.2025.118299. PMID: 40592207.
BibTeX
@article{choi2025-40592207,
author = {Choi, Jae-Won and Im, Joo Young and Balakrishnan, Rengasamy},
title = {{Paeoniflorin exercise-mimetic potential regulates the Nrf2/HO-1/BDNF/CREB and APP/BACE-1/NF-κB/MAPK signaling pathways to reduce cognitive impairments and neuroinflammation in amnesic mouse model}},
journal = {Biomedicine \& Pharmacotherapy},
year = {2025},
doi = {10.1016/j.biopha.2025.118299},
pmid = {40592207},
url = {https://doi.org/10.1016/j.biopha.2025.118299}
}
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