{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:53Z","timestamp":1786951553799,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cardiotoxicity induced by doxorubicin (Dox) significantly contributes to increased mortality among cancer patients, yet available pharmacological interventions remain scarce. Recent studies suggest that ferroptosis is a key mechanism in the development of Dox\u2010induced cardiotoxicity (DIC). Morroniside (Mor), an active iridoid glycoside isolated from\n                    <jats:italic>Cornus officinalis<\/jats:italic>\n                    , exhibits multiple pharmacological properties such as antioxidant, anti\u2010ferroptotic, and anti\u2010inflammatory activities. Given this multi\u2010target profile, Mor shows potential as a treatment option for reducing DIC. This work was designed to examine the association between Mor and DIC. In vivo DIC model, C57BL\/J mice received 5\u2009mg\/kg\/d Mor via oral gavage for 5\u2009weeks. In vitro DIC model, H9c2 cells were exposed to 10\u2009\u03bcM Mor over a 48\u2010h period. Cardiac injury markers were quantified in serum and cell culture supernatants. Biochemical assays, western blotting, cellular immunofluorescence, and DHE\/ROS staining were employed to evaluate ferroptosis and oxidative stress. Mor administration substantially reduced the levels of cardiac injury biomarkers while simultaneously attenuating ferroptosis and oxidative stress in vivo. In cellular models, Mor exhibited potent anti\u2010ferroptotic and antioxidant effects through Nrf2 pathway activation. Further mechanistic studies identified PI3K\/AKT pathway as the upstream regulator of Nrf2 activation in response to Mor treatment. Our study provided the first evidence for Mor's cardioprotective effects against DIC. Mechanistically, Mor attenuated DIC by suppressing ferroptosis and reducing oxidative stress via activation of the PI3K\/AKT\/Nrf2\/HO\u20101 signaling pathway.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71016","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:35:20Z","timestamp":1785152120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Morroniside Attenuates Doxorubicin\u2010Induced Cardiotoxicity by Activating the PI3K\/AKT\/Nrf2\/HO\u20101 Pathway to Inhibit Ferroptosis and Oxidative Stress"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6957-5702","authenticated-orcid":false,"given":"Zhi\u2010Hui","family":"Lin","sequence":"first","affiliation":[{"name":"Center for Rehabilitation Medicine, Department of Rehabilitation Medicine Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Zhejiang Engineering Research Center for Digital\u2010Intelligent Rehabilitation Equipment Hangzhou Zhejiang P. 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