{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:41:13Z","timestamp":1787330473088,"version":"build-2736575974"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>Pueraria lobata<\/jats:italic>\n                      , 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1907120","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:07:42Z","timestamp":1787328462000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual modulation of the NLRP3\/CASPASE-1 inflammasome pathway and gut microbial metabolism: the antidepressant mechanism of puerarin"],"prefix":"10.3389","volume":"17","author":[{"given":"Yu-ting","family":"Lu","sequence":"first","affiliation":[{"name":"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","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-yue","family":"Chen","sequence":"additional","affiliation":[{"name":"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","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine","place":["Foshan, Guangdong, 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Pharmacol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e15872","DOI":"10.1016\/j.heliyon.2023.e15872","article-title":"Efficacy of puerarin in rats with focal cerebral ischemia through modulation of the SIRT1\/HIF-1\u03b1\/VEGF signaling pathway and its effect on synaptic plasticity","volume":"9","author":"Liu","year":"","journal-title":"Heliyon"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"14864","DOI":"10.1021\/acs.jafc.2c06417","article-title":"Fucoidan ameliorated dextran sulfate sodium-induced ulcerative colitis by modulating gut microbiota and bile acid metabolism","volume":"70","author":"Liu","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.genhosppsych.2020.06.011","article-title":"Post-stroke depression: a 2020 updated review","volume":"66","author":"Medeiros","year":"2020","journal-title":"Gen. Hosp. 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Res."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"111022","DOI":"10.1016\/j.brainresbull.2024.111022","article-title":"Exploring the pathogenesis and treatment of PSD from the perspective of gut microbiota","volume":"215","author":"Shi","year":"2024","journal-title":"Brain Res. Bull."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.jad.2021.04.037","article-title":"Puerarin ameliorates depression-like behaviors of with chronic unpredictable mild stress mice by remodeling their gut microbiota","volume":"290","author":"Song","year":"2021","journal-title":"J. Affect. Disord."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"14925","DOI":"10.3390\/ijms241914925","article-title":"Impact of microbiome\u2013brain communication on neuroinflammation and neurodegeneration","volume":"24","author":"Stolzer","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"12073","DOI":"10.1080\/10408398.2022.2098249","article-title":"Gut firmicutes: relationship with dietary fiber and role in host homeostasis","volume":"63","author":"Sun","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3390\/brainsci14060521","article-title":"Sex-related differences in post-stroke anxiety, depression and quality of life in a cohort of smokers","volume":"14","author":"Su\u00f1er-Soler","year":"2024","journal-title":"Brain Sci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.jare.2024.03.023","article-title":"Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance","volume":"69","author":"Tao","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.bbi.2021.11.023","article-title":"Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: a randomized clinical trial","volume":"100","author":"Tian","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e863","DOI":"10.1038\/tp.2016.124","article-title":"Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke","volume":"6","author":"Vahid-Ansari","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2402152","DOI":"10.1002\/advs.202402152","article-title":"Unraveling the pathogenesis of post-stroke depression in a hemorrhagic mouse model through frontal lobe circuitry and JAK-STAT signaling","volume":"11","author":"Wu","year":"2024","journal-title":"Adv. Sci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"149944","DOI":"10.1016\/j.brainres.2025.149944","article-title":"Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion-induced intestinal barrier injury and neuroinflammation via inhibition of the TLR4\/NLRP3 inflammasome pathway in rats","volume":"1866","author":"Ye","year":"2025","journal-title":"Brain Res."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1987779","DOI":"10.1080\/19490976.2021.1987779","article-title":"Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics","volume":"13","author":"Yuan","year":"2021","journal-title":"Gut Microbes"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s12035-023-03563-w","article-title":"Investigating the potential mechanisms and therapeutic targets of inflammatory cytokines in post-stroke depression","volume":"61","author":"Zhang","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"111050","DOI":"10.1016\/j.pnpbp.2024.111050","article-title":"Circulating interleukins concentrations and post-stroke depression: a systematic review and meta-analysis","volume":"134","author":"Zheng","year":"2024","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1784251","DOI":"10.3389\/fnins.2026.1784251","article-title":"Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework","volume":"20","author":"Zhou","year":"2026","journal-title":"Front. Neurosci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"114660","DOI":"10.1016\/j.expneurol.2023.114660","article-title":"Research progress on post-stroke depression","volume":"373","author":"Zhou","year":"2024","journal-title":"Exp. 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