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Isobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice
Dilpreet Kour, Parul Khajuria, Kuhu Sharma, Alpa Sharma, Ankita Sharma, Syed Mudassir Ali, Priya Wazir, P. Ramajayan et al.. Frontiers in Pharmacology, 2025-03-20
Topic: Brain proteins, microglia and lab models
Background and Aim Alzheimer’s disease (AD) progresses with Aβ plaque deposition and neuroinflammation. Given the complexity of AD pathology, single-target therapies have frequently failed in clinical trials. We hypothesized that a multitarget approach could yield better therapeutic outcomes. To this end, we identified isobavachalcone (IBC), a natural compound with dual pharmacological activity in reducing Aβ plaques and neuroinflammation. Experimental Procedure Primary astrocytes were isolated from 3 to 4 days old C57BL/6J mice pups for in-vitro assays, while in-vivo studies were conducted on 5x-FAD mice. Protein alterations were evaluated using ELISA, western blotting, immunocytochemistry, and immunohistochemistry. Behavioral analyses included the radial arm maze, open field, and rotarod tests. Data from all in vitro and in vivo experiments were analyzed by using one-way ANOVA and post-hoc Bonferroni tests. Results In-vitro analyses in astrocytes demonstrated that IBC at 5 and 10 μM concentrations induce AMPK phosphorylation through CAMKK2, promoting autophagy and inhibiting the NLRP3 inflammasome in primary astrocytes. IBC-treated astrocytes exhibited significant clearance of extracellular amyloid beta. Mechanistic studies highlighted autophagy as a key factor in reducing both NLRP3 inflammasome activity and Aβ levels. Two months of treatment of 5x-FAD mice with IBC at 25 and 50 mg/kg significantly improved cognitive functions, as evidenced by enhanced memory and motor performance in behavioral tests. Subsequent brain tissue analysis revealed that IBC upregulated autophagic proteins to reduce the brain’s amyloid beta levels, resulting in decreased expression of neuroinflammation markers. Conclusion IBC effectively ameliorates AD pathology through autophagy-mediated clearance of Aβ and suppressing neuroinflammation in 5x-FAD mice.
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APA 7th
Kour, D., Khajuria, P., Sharma, K., Sharma, A., Sharma, A., Ali, S. M., et al. (2025). Isobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2025.1525364
Vancouver
Kour D, Khajuria P, Sharma K, Sharma A, Sharma A, Ali SM, et al. Isobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice. Frontiers in Pharmacology. 2025. doi:10.3389/fphar.2025.1525364. PMID: 40183098.
BibTeX
@article{kour2025-40183098,
author = {Kour, Dilpreet and Khajuria, Parul and Sharma, Kuhu and Sharma, Alpa and Sharma, Ankita and Ali, Syed Mudassir and Wazir, Priya and Ramajayan, P. and others},
title = {{Isobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice}},
journal = {Frontiers in Pharmacology},
year = {2025},
doi = {10.3389/fphar.2025.1525364},
pmid = {40183098},
url = {https://doi.org/10.3389/fphar.2025.1525364}
}
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.
Key findings
- Results In-vitro analyses in astrocytes demonstrated that IBC at 5 and 10 μM concentrations induce AMPK phosphorylation through CAMKK2, promoting autophagy and inhibiting the NLRP3 inflammasome in primary astrocytes.
- IBC-treated astrocytes exhibited significant clearance of extracellular amyloid beta.
- Two months of treatment of 5x-FAD mice with IBC at 25 and 50 mg/kg significantly improved cognitive functions, as evidenced by enhanced memory and motor performance in behavioral tests.
- Subsequent brain tissue analysis revealed that IBC upregulated autophagic proteins to reduce the brain’s amyloid beta levels, resulting in decreased expression of neuroinflammation markers.
Why it matters
In astrocyte cultures and 5x-FAD mice, isobavachalcone promoted clearance of amyloid beta and inhibited the NLRP3 inflammasome, and treated mice showed improved memory and motor performance. These are laboratory and animal results, so the compound has not been shown to treat Alzheimer's disease in people.
Study details
- Study designpost-hoc analysis
- 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 (Frontiers in Pharmacology) |
| Journal's citation record | 2 / 4 | Frontiers in Pharmacology: journal h-index 242 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “post-hoc analysis”, which our rubric does not rank (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 |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.7× 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 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ajay Kumar: h-index 37 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | National Chemical Laboratory: institution h-index 392 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40183098) |
| 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.2025.1525364
- PubMed: 40183098
- 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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