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Ginsenoside Rc mitigates hippocampal neuronal damage and cognitive impairment in vascular dementia rats via the pY705-Stat3/Foxo3a and pS727-Stat3/GRIM-19 pathways
Yuying Wu, Zhizhen Zhang, Xiao‐Yuan Lian. Journal of Ginseng Research, 2025-07-24
Topic: Brain proteins, microglia and lab models
ABSTRACT Background Vascular dementia (VaD), the second most common cause of dementia, lacks effective treatments. Ginsenoside Rc (GRc) has demonstrated therapeutic potential, but its role in VaD remains unclear. This study investigates the protective effects of GRc in VaD and its underlying mechanisms. Methods Cognitive function was assessed using novel object recognition and Morris water maze tests. Neuronal and glial status in the cortex and hippocampus were evaluated by immunohistochemistry, Nissl staining, immunofluorescence, transmission electron microscopy, and Western blotting. Drug target identification was performed through molecular docking, molecular dynamics simulations, and cellular thermal shift assay. Apoptosis markers, along with pY705-Stat3/Foxo3a/Nrf2 and pS727-Stat3/GRIM-19/Sirt1/PGC1α pathway-related factors, were analyzed by cell viability assay, Western blotting, immunoprecipitation, and commercial assay kits. Results GRc ameliorated cognitive deficits in VaD rats, attenuating synaptic disruption and neuronal apoptosis in the hippocampal CA1 region. GRc bound to Stat3 and promoted its phosphorylation at Y705 and S727. It further enhanced catalase and SOD activity through pY705-Stat3-mediated Foxo3a activation and upregulated GSR, Gpx4, and GSH via the Nrf2 pathway. Moreover, GRc stabilized the pS727-Stat3/GRIM-19 complex, facilitating mitochondrial translocation of pS727-Stat3, which enhanced mitochondrial Complex I and II activities, increased NAD + levels, and activated the Sirt1/PGC1α pathway, promoting mitochondrial biogenesis and ATP production. Conclusion GRc exerted neuroprotective effects in VaD by targeting Stat3 and driving its dual-phosphorylation. Through the pY705-Stat3/Foxo3a and pS727-Stat3/GRIM-19 pathways, GRc alleviated hippocampal neuronal apoptosis and synaptic dysfunction, thereby improving cognitive function in VaD rats.
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APA 7th
Wu, Y., Zhang, Z., & Lian, X. (2025). Ginsenoside Rc mitigates hippocampal neuronal damage and cognitive impairment in vascular dementia rats via the pY705-Stat3/Foxo3a and pS727-Stat3/GRIM-19 pathways. Journal of Ginseng Research. https://doi.org/10.1016/j.jgr.2025.07.003
Vancouver
Wu Y, Zhang Z, Lian X. Ginsenoside Rc mitigates hippocampal neuronal damage and cognitive impairment in vascular dementia rats via the pY705-Stat3/Foxo3a and pS727-Stat3/GRIM-19 pathways. Journal of Ginseng Research. 2025. doi:10.1016/j.jgr.2025.07.003. PMID: 41268317.
BibTeX
@article{wu2025-41268317,
author = {Wu, Yuying and Zhang, Zhizhen and Lian, Xiao‐Yuan},
title = {{Ginsenoside Rc mitigates hippocampal neuronal damage and cognitive impairment in vascular dementia rats via the pY705-Stat3/Foxo3a and pS727-Stat3/GRIM-19 pathways}},
journal = {Journal of Ginseng Research},
year = {2025},
doi = {10.1016/j.jgr.2025.07.003},
pmid = {41268317},
url = {https://doi.org/10.1016/j.jgr.2025.07.003}
}
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.
Key findings
- Ginsenoside Rc (GRc) has demonstrated therapeutic potential, but its role in VaD remains unclear.
- Results GRc ameliorated cognitive deficits in VaD rats, attenuating synaptic disruption and neuronal apoptosis in the hippocampal CA1 region.
Why it matters
In rats with vascular dementia, ginsenoside Rc improved cognitive deficits and reduced synaptic disruption and neuronal apoptosis in the hippocampal CA1 region. This is an animal study, so it does not yet show that ginsenoside Rc treats dementia in humans.
Study details
- Evidence strengthLow
How this study scored 37/100
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 (Journal of Ginseng Research) |
| Journal's citation record | 1 / 4 | Journal of Ginseng Research: journal h-index 84 (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 | 2 / 6 | Cited 2.9× 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 | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Xiao‐Yuan Lian: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Zhejiang University: institution h-index 1,040 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41268317) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.jgr.2025.07.003
- PubMed: 41268317
- Original source →
- Free full text: Journal of Ginseng Research →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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