{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T06:48:02Z","timestamp":1774594082090,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>NOD-like receptor protein 3 (NLRP3) inflammasome\u2013driven neuroinflammation contributes to ischemic stroke injury. Atractylodin (ART) shows anti-inflammatory activity, but its neuroprotective potential and mechanistic links to NLRP3 signaling after cerebral ischemia\u2013reperfusion (I\/R) injury remain to be defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      BV2 microglia were subjected to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R), and rats underwent middle cerebral artery occlusion (MCAO) followed by reperfusion. ART was administered after reperfusion\n                      <jats:italic>in vivo<\/jats:italic>\n                      (10 or 30\u202fmg\/kg, once daily for 3\u202fdays) and during reoxygenation\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Neurobehavioral outcomes and infarct volume were assessed in MCAO rats, along with measurements of neuronal apoptosis. NLRP3 inflammasome activation, gasdermin D (GSDMD)\u2013dependent pyroptosis, pro-inflammatory cytokines, and microglial polarization markers were evaluated using immunoblotting, immunofluorescence, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In OGD\/R-stimulated BV2 microglia, ART suppressed NLRP3 inflammasome activation and reduced GSDMD cleavage, accompanied by decreased IL-1\u03b2 and IL-18 production. In the MCAO model, ART significantly improved neurological outcomes and reduced infarct volume and neuronal apoptosis. These protective effects were linked to a reduction in the expression of NLRP3 pathway components (NLRP3, ASC, and caspase-1) and GSDMD-N. Additionally, there was a shift in microglial responses toward an anti-inflammatory (M2-like) profile, which led to a decrease in pro-inflammatory markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ART confers neuroprotection in experimental ischemic stroke by inhibiting NLRP3 inflammasome\u2013associated pyroptosis and modulating microglial inflammatory polarization, supporting its potential as a therapeutic candidate for ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1754614","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:19:23Z","timestamp":1774588763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Atractylodin alleviates neuroinflammation and protects neurological function after ischemic stroke in association with reduced NLRP3 inflammasome activation"],"prefix":"10.3389","volume":"17","author":[{"given":"Qingyao","family":"Ouyang","sequence":"first","affiliation":[{"name":"College of Basic Medical Sciences, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiying","family":"Yang","sequence":"additional","affiliation":[{"name":"Nanyang Second General Hospital","place":["Nanyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoi Leong","family":"Lee","sequence":"additional","affiliation":[{"name":"Biomedical Electronic Engineering Programme, Faculty of Electronic Engineering and Technology, Universiti Malaysia Perlis","place":["Arau, Perlis, Malaysia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyu","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, China Three Gorges University","place":["Yichang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the global burden of disease study 2019","volume":"20","year":"2021","journal-title":"Lancet Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1159\/000506396","article-title":"Global, regional and country-specific burden of ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage: a systematic analysis of the global burden of disease study 2017","volume":"54","author":"Krishnamurthi","year":"2020","journal-title":"Neuroepidemiology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"7609","DOI":"10.3390\/ijms21207609","article-title":"Pathophysiology and treatment of stroke: present status and future perspectives","volume":"21","author":"Kuriakose","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/S1474-4422(16)00114-9","article-title":"Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation","volume":"15","author":"Chamorro","year":"2016","journal-title":"Lancet 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and M2 microglia exist?","volume":"19","author":"Ransohoff","year":"2016","journal-title":"Nat Neurosci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.3892\/mmr.2020.11003","article-title":"Modulators of microglia activation and polarisation in ischemic stroke (review)","volume":"21","author":"Jiang","year":"2020","journal-title":"Mol Med Rep"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"102297","DOI":"10.1016\/j.redox.2022.102297","article-title":"Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1\/M2 phenotypic polarisation","volume":"52","author":"Wang","year":"2022","journal-title":"Redox Biol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2666","DOI":"10.1111\/cns.14211","article-title":"Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA\/p38MAPK signaling pathway","volume":"29","author":"Li","year":"2023","journal-title":"CNS Neurosci 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Neuroinflammation"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41423-021-00670-3","article-title":"An update on the regulatory mechanisms of NLRP3 inflammasome activation","volume":"18","author":"Paik","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"167379","DOI":"10.1016\/j.jmb.2021.167379","article-title":"Pyroptosis, and its role in central nervous system disease","volume":"434","author":"Hu","year":"2022","journal-title":"J Mol Biol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12974-022-02674-w","article-title":"Delayed NLRP3 inflammasome inhibition ameliorates subacute stroke progression in mice","volume":"20","author":"Bellut","year":"2023","journal-title":"J Neuroinflammation"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.phrs.2019.01.035","article-title":"NLRP3 inflammasome inhibition with MCC950 improves 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