{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:20:03Z","timestamp":1788250803669,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intracerebral hemorrhage (ICH) remains the most severe stroke subtype with high mortality and disability rates. Although apigenin has shown cerebroprotective potential in preclinical studies, its mechanism of action, particularly in hypertensive ICH, remains poorly understood. This study investigates the molecular pathway through which apigenin confers protection against hypertensive ICH. We employed a hypertensive ICH mouse model treated with varying apigenin doses. Through transcriptomic profiling, molecular docking, surface plasmon resonance (SPR), and pull\u2010down assay, we identified peroxiredoxin 2 (PRDX2) as a direct target of apigenin.\n                    <jats:italic>Prdx2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice and recombinant human thioredoxin 1 (rhTrx1) rescue experiments were utilized to validate the signaling pathway. Histological analysis, western blot, immunofluorescence, and zymography were applied to assess hemorrhage, oxidative stress, inflammation, and extracellular matrix (ECM) remodeling. Apigenin administration significantly reduced ICH incidence, hemorrhage volume, and area while enhancing vascular integrity, independent of blood pressure changes. We identified PRDX2 as a direct binding partner of apigenin, with their interaction stabilizing PRDX2 expression. PRDX2 deficiency abolished apigenin's protective effects and exacerbated oxidative stress, neuroinflammation, and vascular damage. Furthermore, apigenin upregulated Trx1 expression via PRDX2, and rhTrx1 administration rescued the protective phenotype in\n                    <jats:italic>Prdx2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice by reducing oxidative damage, inflammatory cell infiltration, and vascular smooth muscle cell apoptosis. Our study elucidates a novel apigenin\u2010PRDX2\u2010Trx1 antioxidant signaling pathway that protects against hypertensive ICH through blood pressure\u2010independent mechanisms. These findings not only provide a mechanistic foundation for developing apigenin\u2010based therapeutics for cerebrovascular diseases, but also offer novel strategies and entry points for future clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70439","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:11:31Z","timestamp":1788250291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Apigenin Protects Hypertensive Intracerebral Hemorrhage by Regulating Trx1 Through Binding to\n                    <scp>PRDX2<\/scp>"],"prefix":"10.1002","author":[{"given":"Hao\u2010chen","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"},{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Fuwai Central\u2010China Hospital, Central\u2010China Branch of National Center for Cardiovascular Diseases  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010ying","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie\u2010Dan","family":"Ping","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010hua","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Sports Medicine Wuhan Institute of Physical Education  Wuhan Hubei Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1642-003X","authenticated-orcid":false,"given":"Jing\u2010zhou","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"},{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Fuwai Central\u2010China Hospital, Central\u2010China Branch of National Center for Cardiovascular Diseases  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"},{"name":"National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine Fuwai Central\u2010China Hospital, Central\u2010China Branch of National Center for Cardiovascular Diseases  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2379"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26291"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2023.155080"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.11327"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2741\/3859"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234\u2010014\u20101423\u20102"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci172841"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007\u20100216"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(21)00252\u20100"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012\u2010021\u201009662\u20101"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.108942"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2018.07.002"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000167694.58419.a2"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010019\u201003869\u20104"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2022.114263"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201045206\u2010y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132939"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102002\u201008\u20102548"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2314741"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016990\u20103"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x18815791"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.65277"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1553081"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/circgenetics.114.000696"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41440\u2010019\u20100207\u20109"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167488"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.115.010920"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156577"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166317"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.095"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.692798"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1362301"},{"issue":"3","key":"e_1_2_11_35_1","first-page":"249","article-title":"Study of Cerebral Vascular Structures in Hypertensive Intracerebral Haemorrhage","volume":"46","author":"Ple\u015fea I. 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