{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:11:30Z","timestamp":1792181490813,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017531","name":"Medical and Health Research Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2025KY1258"],"award-info":[{"award-number":["2025KY1258"]}],"id":[{"id":"10.13039\/501100017531","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171366"],"award-info":[{"award-number":["82171366"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intracerebral hemorrhage (ICH) is a life\u2010threatening stroke subtype that lacks effective drug therapy. In the context of ICH, neuroinflammation, and ferroptosis are key contributors to secondary brain injury. In this study, we assessed the neuroprotective effects of matrine (MAT) and its mechanism of action involving the HMGB1\/RAGE axis in an ICH mouse model. ICH was induced in mice by autologous blood injection. MAT (1.5 or 20\u2009mg\/kg) was administered orally 5\u2009min postinduction. ICH significantly upregulated RAGE and its associated proteins (HMGB1, protein kinase C [PKC], phospholipase C [PLC], and \u03b2\u2010amyloid), confirming pathway activation. Molecular docking revealed a specific hydrogen bond interaction between MAT and RAGE but not with PKC or PLC. MAT improved neurological performance, reduced hematoma volume and brain edema, and restored blood\u2013brain barrier integrity through upregulation of tight junction proteins (ZO\u20101, Occludin, Claudin\u20104). MAT suppressed activation of the HMGB1\/RAGE pathway and downstream kinases JNK, p38, ERK1\/2, and NF\u2010\u03baB p65. It also decreased IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1 levels, reduced Bax, increased Bcl\u20102, and mitigated neuronal apoptosis. Additionally, MAT lowered Fe\n                    <jats:sup>2+<\/jats:sup>\n                    accumulation, inhibited ACSL4, and restored GPX4 levels, indicating ferroptosis suppression. RAGE knockdown mimicked the effects of MAT and negated its therapeutic benefits. MAT induced no detectable liver or kidney toxicity. This study is the first to demonstrate that MAT alleviates ICH\u2010induced neurological deficits by targeting the HMGB1\/RAGE axis\u2010mediated ferroptosis, thereby extending the current understanding of the neuroprotective mechanisms of MAT beyond its known anti\u2010inflammatory and antioxidant actions.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70157","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T10:37:46Z","timestamp":1765881466000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Matrine Attenuates Neurological Deficits and Neuroinflammation by Inhibiting the\n                    <scp>HMGB1<\/scp>\n                    \/\n                    <scp>RAGE<\/scp>\n                    Axis and Ferroptosis in Intracerebral Hemorrhage Mice"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9863-1504","authenticated-orcid":false,"given":"Pan\u2010Di","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao\u2010Tao","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010Yang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Na","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Xiang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao\u2010Song","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo University  Ninbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4273-5843","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Affiliated Lihuili Hospital of Ningbo 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