{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:12:29Z","timestamp":1780913549045,"version":"3.54.1"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The neuroinflammatory cascade triggered by cerebral ischemia\u2013reperfusion injury (CIRI) represents a pivotal pathological mechanism driving neuronal death and dysfunction. Forsythoside A (FA) exhibits anti\u2010inflammatory properties, but its effects on CIRI and potential mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate whether FA improves astrocyte pyroptosis and alleviates neuroinflammatory damage in CIRI via modulating the Toll\u2010like receptor 4 (TLR4)\/nuclear factor \u03baB (NF\u2010\u03baB)\/NLRP3 pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The middle cerebral artery occlusion reperfusion (MCAO\/R) mouse model was established, with cerebral infarction volume observed through TTC staining, and neurological scores assessed. The effects of FA on cerebral cortical damage, neuroinflammation, apoptosis, and pyroptosis were observed by pathological staining. An oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) U251 human astroglioma cell model was established, and the protective impact of FA on cell viability was detected through the cell counting kit\u20108 assay. The release of lactate dehydrogenase (LDH) was measured by the LDH assay Kit, and cell pyroptosis was evaluated through Hoechst 33,342\/PI staining. Inflammatory factor levels were detected by ELISA kits, with pyroptosis\u2010related and TLR4\/NF\u2010\u03baB\/NLRP3 pathway\u2010related protein levels evaluated through Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FA reduced the infarct volume, ameliorated brain tissue pathological damage, reduced activated astrocytes, and inhibited neuronal apoptosis in MCAO\/R mice. FA also alleviated inflammatory cell infiltration in brain tissue and declined pro\u2010inflammatory factor levels in serum. In addition, FA suppressed TLR4 and p\u2010NF\u2010\u03baB p65 expression and NLRP3 inflammasome activation in astrocytes. OGD\/R caused decreased U251 cell viability, increased LDH release, and pyroptosis rate, while FA treatment could reverse the above effects. Mechanistically, FA hindered the TLR4\/NF\u2010\u03baB pathway, down\u2010regulated NLRP3 and pyroptosis\u2010related proteins. The TLR4 agonist LPS weakened the protective impact of FA on MCAO\/R mice and OGD\/R cell models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FA alleviates neuroinflammatory damage through inhibiting the TLR4\/NF\u2010\u03baB axis and blocking NLRP3 inflammasome\u2010induced astrocyte pyroptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70867","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:37:09Z","timestamp":1775641029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Forsythoside A Alleviates Neuroinflammatory Damage via Inhibiting\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    \/\n                    <scp>NLRP3<\/scp>\n                    Activation\u2010Induced Astrocyte Pyroptosis in Cerebral Ischemia\u2013Reperfusion"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9457-6786","authenticated-orcid":false,"given":"Yupeng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Aviation General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanwei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Aviation General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Aviation General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Aviation General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shewei","family":"Guo","sequence":"additional","affiliation":[{"name":"Neurosurgical Department The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114817"},{"key":"e_1_2_13_3_1","first-page":"58","article-title":"Stroke in Asia","volume":"14","author":"Tan K. 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