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Kai-Xin-San ameliorates mild cognitive impairment in SAMP8 mice by inhibiting neuroinflammation and pyroptosis via NLRP3/Caspase-1 pathway modulation
Shu Liu, Xiaochen Song, Yuefeng Sun, Ailin Sun, Yang Li, Yuyu Li, Jing Chen. Frontiers in Pharmacology, 2025-03-13
Topic: Brain proteins, microglia and lab models
Mild Cognitive Impairment (MCI) represents a critical stage between normal aging and dementia, with limited effective interventions currently available. This study investigated the effects of Kai-Xin-San (KXS), a traditional Chinese herbal formula, on cognitive function, neuroinflammation, and pyroptosis in a senescence-accelerated prone 8 (SAMP8) mouse model of MCI. SAMP8 mice were treated with KXS for 8 weeks, followed by behavioral tests, biochemical analyses, and histological examinations. KXS significantly improved spatial memory, working memory, and executive function in SAMP8 mice. Furthermore, KXS treatment reduced β-amyloid (Aβ) deposition, attenuated neuroinflammation by decreasing pro-inflammatory cytokine levels (IL-1β, IL-18, IL-6, TNF-α), and inhibited microglia activation in the hippocampus. Notably, KXS suppressed pyroptosis by modulating the NLRP3/Caspase-1 signaling pathway, as evidenced by reduced expression of NLRP3, ASC, Caspase-1, and GSDMD. These effects were abolished by treatment with the NLRP3 inflammasome agonist Nigericin, suggesting that NLRP3 inhibition is a key mechanism of KXS action. Our findings reveal a novel mechanism by which KXS exerts neuroprotective effects in MCI, simultaneously targeting Aβ accumulation, neuroinflammation, and pyroptosis. This multi-target approach of KXS highlights its potential as a therapeutic strategy for MCI and warrants further investigation in clinical settings.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Liu, S., Song, X., Sun, Y., Sun, A., Li, Y., Li, Y., et al. (2025). Kai-Xin-San ameliorates mild cognitive impairment in SAMP8 mice by inhibiting neuroinflammation and pyroptosis via NLRP3/Caspase-1 pathway modulation. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2025.1528011
Vancouver
Liu S, Song X, Sun Y, Sun A, Li Y, Li Y, et al. Kai-Xin-San ameliorates mild cognitive impairment in SAMP8 mice by inhibiting neuroinflammation and pyroptosis via NLRP3/Caspase-1 pathway modulation. Frontiers in Pharmacology. 2025. doi:10.3389/fphar.2025.1528011. PMID: 40183082.
BibTeX
@article{liu2025-40183082,
author = {Liu, Shu and Song, Xiaochen and Sun, Yuefeng and Sun, Ailin and Li, Yang and Li, Yuyu and Chen, Jing},
title = {{Kai-Xin-San ameliorates mild cognitive impairment in SAMP8 mice by inhibiting neuroinflammation and pyroptosis via NLRP3/Caspase-1 pathway modulation}},
journal = {Frontiers in Pharmacology},
year = {2025},
doi = {10.3389/fphar.2025.1528011},
pmid = {40183082},
url = {https://doi.org/10.3389/fphar.2025.1528011}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- KXS significantly improved spatial memory, working memory, and executive function in SAMP8 mice.
- These effects were abolished by treatment with the NLRP3 inflammasome agonist Nigericin, suggesting that NLRP3 inhibition is a key mechanism of KXS action.
- Our findings reveal a novel mechanism by which KXS exerts neuroprotective effects in MCI, simultaneously targeting Aβ accumulation, neuroinflammation, and pyroptosis.
Why it matters
In SAMP8 mice, Kai-Xin-San improved memory and reduced amyloid beta deposition, neuroinflammation, and pyroptosis via the NLRP3/Caspase-1 pathway. This is animal research, so it does not yet show that this herbal formula treats mild cognitive impairment or prevents dementia in people.
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 randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Pharmacology) |
| Journal's citation record | 2 / 4 | Frontiers in Pharmacology: journal h-index 242 (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 “mice”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.8× 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 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jing Chen: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Qilu University of Technology: institution h-index 230 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40183082) |
| 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: 10.3389/fphar.2025.1528011
- PubMed: 40183082
- Original source →
- Free full text: Frontiers in Pharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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