{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T14:21:40Z","timestamp":1794406900094,"version":"4.9.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Endothelial ferroptosis is a crucial pathogenic driver of atherosclerosis (AS) progression. Protosappanin A (PTA), a bioactive compound from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Caesalpinia sappan<\/jats:italic>\n                    <\/jats:styled-content>\n                    L., protects cardiovascular vessels by regulating ferroptosis. However, whether PTA inhibits AS specifically through suppressing endothelial ferroptosis remains unclear. To address this, ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were fed a high\u2010fat diet for 16\u2009weeks to induce atherosclerosis, and PTA or simvastatin was administered daily from Week 4 through Week 16 (12\u2009weeks of intervention). PTA markedly reduced aortic plaque area (en face Oil Red O and H&amp;E staining) and improved serum lipid profiles (TG, TC, LDL\u2010C, HDL\u2010C). It also alleviated endothelial injury, evidenced by decreased VCAM\u20101 and ICAM\u20101 expression. Mechanistically, PTA ameliorated mitochondrial ferroptosis in endothelial cells, lowered intracellular Fe\n                    <jats:sup>2+<\/jats:sup>\n                    and lipid peroxidation (MDA, lipid ROS), and restored the expression of GPX4, xCT, and FTH1. Immunofluorescence confirmed that PTA upregulated GPX4 within the aortic endothelium. To explore the underlying mechanism, we performed RNA\u2010seq on ox\u2010LDL\u2010treated HUVECs and integrated the data with ferroptosis\u2010related databases. MDM2 was identified as a key target, which was validated by qPCR and Western blotting. Overexpression of MDM2 activated endothelial ferroptosis and reversed the protective effects of PTA both in\u00a0vitro and in\u00a0vivo. Collectively, these findings demonstrate that PTA alleviates AS by suppressing endothelial ferroptosis via the MDM2\/GPX4 axis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70443","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:23:13Z","timestamp":1788920593000},"page":"6450-6467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protosappanin A Alleviates Atherosclerosis by Regulating the\n                    <scp>MDM2<\/scp>\n                    \/\n                    <scp>GPX4<\/scp>\n                    Axis\u2010Mediated Endothelial Ferroptosis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3597-6644","authenticated-orcid":false,"given":"Jiamei","family":"Fu","sequence":"first","affiliation":[{"name":"The First Hospital Affiliated to Heilongjiang University of Chinese Medicine  Harbin China"},{"name":"Postdoctoral Research 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