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Dual modulation of the NLRP3/CASPASE-1 inflammasome pathway and gut microbial metabolism: the antidepressant mechanism of puerarin.

Overview

Authors: Yu-ting Lu1, Yue-yue Chen1,2, Na-na Ding1, Ling-wen Meng3, Jia-jia Yuan4, Ze-xiang Huang5, Jing-bo Hu1, Jia-xi Tong6, Ying-ren Zhang1, Nan Nan6, Dong-dong Liu1, Kai-rui Tang7, Xiang Luo5, Xia Li1, Wen-zhi Hao1, Jia-xu Chen1,6
  1. Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Guangdong Second Provincial General Hospital, Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China
  2. Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, Guangdong, China
  3. Institute of Biomedical Translational Research, Jinan University, Guangzhou, China
  4. Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Ministry of Education, School of Medicine, Jinan University, Guangzhou, China
  5. Department of Food Science and Engineering, Jinan University, Guangzhou, China
  6. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
  7. School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
Institutions: Jinan University (China); University of Jinan (China); Beijing University of Chinese Medicine (China); Guangzhou University of Chinese Medicine (China)
Journal: Frontiers in microbiology, volume 17, article 1907120
Dates: received 12 June 2026; accepted 20 July 2026; published online 21 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3389/fmicb.2026.1907120 · PMID 42699624 · PMCID PMC13543961 · OpenAlex W7203934667
Open access: gold, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: mouse (organism), stroke (population), depression (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions
Keywords: gut-brain axis, microbial metabolism, NLRP3/CASPASE-1 inflammasome, post-stroke depression, puerarin
Topic: Tryptophan and brain disorders (Biological Psychiatry, Neuroscience), according to OpenAlex
Citations: not cited yet (Europe PMC); 57 references in the paper

Abstract

Background: Post-stroke depression (PSD) is the most common neuropsychiatric complication following stroke. Puerarin (PU), the principal bioactive compound extracted from the medicinal and edible plant Pueraria lobata, has shown beneficial therapeutic effects in both depression and stroke. However, the therapeutic effect of PU on PSD and its underlying mechanisms remain unclear. This study investigates the therapeutic efficacy of PU in ameliorating abnormal behaviors in PSD mice and elucidates the roles of intestinal microbiota disorder, intestinal barrier damage, activation of the NLRP3/CASPASE-1 inflammasome in the hippocampus, and dysregulated inflammatory cytokine production in the pathogenesis of PSD.

Methods: To investigate the ameliorative effect of PU on behavioral abnormalities and to clarify the role of intestinal microbiota regulation in the therapeutic effects of PU in PSD mice, various methodologies were employed, including a PSD model, behavioral tests, network pharmacology, hematoxylin-and-eosin staining, ultrastructural morphology, enzyme-linked immunosorbent assay, western blotting, 16S rRNA sequencing, metabolomic analyses, and fecal microbiota transplantation (FMT).

Results: Oral administration of PU could effectively alleviate depressive-like behaviors in PSD mice, repair the damaged colonic mucosa, and increase the expression of occludin and ZO-1. Network pharmacology analysis indicated that the NLRP3/CASPASE-1 inflammasome pathway was a potential therapeutic target of PU, and PU inhibited activation of the hippocampal NLRP3/CASPASE-1 inflammasome. Additionally, PU suppressed pro-inflammatory cytokines in both the hippocampus and serum. PU restored the intestinal microbiota and regulated the microbial metabolism of PSD mice. More importantly, fecal microbiota transplantation from PSD mice reproduced depressive-like behaviors, while fecal microbiota transplantation from PU-treated mice (PU-FMT) prominently relieved depressive-like behaviors in PSD mice.

Conclusion: Our findings indicate that PU reduces depressive-like behaviors in PSD mice by modulating the intestinal microbiota and microbial metabolism and inhibiting the NLRP3/CASPASE-1 inflammasome.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

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Data

Datasets cited

Data availability statement

The data presented in this paper are stored in NCBI SRA database under accession number PRJNA1501384: https://www.ncbi.nlm.nih.gov/sra/PRJNA1501384.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 16 authors, 5 keywords, 57 references.

Cite

This paper

Lu, Y.-t., Chen, Y.-y., Ding, N.-n., Meng, L.-w., Yuan, J.-j., Huang, Z.-x., Hu, J.-b., Tong, J.-x., Zhang, Y.-r., Nan, N., Liu, D.-d., Tang, K.-r., Luo, X., Li, X., Hao, W.-z., & Chen, J.-x. (2026). Dual modulation of the NLRP3/CASPASE-1 inflammasome pathway and gut microbial metabolism: the antidepressant mechanism of puerarin. Frontiers in microbiology, 17, 1907120. https://doi.org/10.3389/fmicb.2026.1907120

BibTeX

@article{lu2026dual,
author = {Lu, Yu-ting and Chen, Yue-yue and Ding, Na-na and Meng, Ling-wen and Yuan, Jia-jia and Huang, Ze-xiang and Hu, Jing-bo and Tong, Jia-xi and Zhang, Ying-ren and Nan, Nan and Liu, Dong-dong and Tang, Kai-rui and Luo, Xiang and Li, Xia and Hao, Wen-zhi and Chen, Jia-xu},
title = {{Dual modulation of the NLRP3/CASPASE-1 inflammasome pathway and gut microbial metabolism: the antidepressant mechanism of puerarin}},
journal = {Frontiers in microbiology},
year = {2026},
month = aug,
volume = {17},
pages = {1907120},
publisher = {Frontiers Media SA},
issn = {1664-302X},
doi = {10.3389/fmicb.2026.1907120},
url = {https://doi.org/10.3389/fmicb.2026.1907120},
pmid = {42699624},
pmcid = {PMC13543961}
}

RIS

TY - JOUR
AU - Lu, Yu-ting
AU - Chen, Yue-yue
AU - Ding, Na-na
AU - Meng, Ling-wen
AU - Yuan, Jia-jia
AU - Huang, Ze-xiang
AU - Hu, Jing-bo
AU - Tong, Jia-xi
AU - Zhang, Ying-ren
AU - Nan, Nan
AU - Liu, Dong-dong
AU - Tang, Kai-rui
AU - Luo, Xiang
AU - Li, Xia
AU - Hao, Wen-zhi
AU - Chen, Jia-xu
TI - Dual modulation of the NLRP3/CASPASE-1 inflammasome pathway and gut microbial metabolism: the antidepressant mechanism of puerarin
T2 - Frontiers in microbiology
J2 - Front Microbiol
PY - 2026
DA - 2026/08/21
VL - 17
SP - 1907120
SN - 1664-302X
PB - Frontiers Media SA
DO - 10.3389/fmicb.2026.1907120
UR - https://doi.org/10.3389/fmicb.2026.1907120
LA - en
ER -

CSL-JSON

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