{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:42:56Z","timestamp":1792212176848,"version":"4.4.0"},"reference-count":76,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Pathological cardiac hypertrophy is initially an adaptive response to sustained mechanical, neurohormonal, or metabolic stress; however, it can progress to fibrosis, contractile dysfunction, arrhythmia, and heart failure. Ferroptosis is a type of regulated cell death caused by iron\u2010dependent phospholipid peroxidation. Evidence consistent with ferroptosis, such as disrupted iron homeostasis, lipid peroxidation, mitochondrial dysfunction and impaired antioxidant defense, has been reported in experimental models of pathological cardiac hypertrophy; however, these findings do not by themselves establish ferroptosis as a cause of hypertrophic remodeling. Astragaloside IV (AS\u2010IV) is a cycloartane\u2010type triterpene saponin from Astragalus species that has shown anti\u2010hypertrophic, antioxidant, anti\u2010inflammatory, metabolic\u2010regulatory and mitochondrial\u2010protective effects in experimental cardiovascular models. AS\u2010IV has also shown anti\u2010ferroptotic effects in several cardiac and extra\u2010cardiac disease models by means of Nrf2\u2010centred antioxidant defense, regulation of SLC7A11\/GPX4, p53 signaling, CD36\u2010dependent lipid handling, and 14\u20103\u20103\u03b7\u2010linked regulation of GPX4 stability. Nevertheless, whether ferroptosis inhibition directly contributes to the anti\u2010hypertrophic effect of AS\u2010IV in pathological cardiac hypertrophy remains unproven because direct causal validation in dedicated hypertrophy models is lacking. This review collects evidence on the biology of ferroptosis in pathological cardiac hypertrophy, the established anti\u2010hypertrophic pharmacology of AS\u2010IV, its reported anti\u2010ferroptotic effects, and relevant pharmacokinetic considerations. Based on this, we propose that AS\u2010IV may reduce the susceptibility of cardiomyocytes to ferroptosis and thus partially inhibit pathological cardiac remodeling; however, this is not yet a proven mechanism. Direct verification requires etiologically distinct hypertrophy models, multi\u2010modal ferroptosis measurements, targeted genetic or pharmacological disruption, dose\u2013response and pharmacokinetic experiments, and cell\u2010type\u2010resolved analysis.<\/jats:p>","DOI":"10.1002\/prp2.70334","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:19:46Z","timestamp":1792210786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragaloside\n                    <scp>IV<\/scp>\n                    and Ferroptosis Modulation in Pathological Cardiac Hypertrophy: Current Evidence, an Integrative Hypothesis, and Future Directions"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5358-624X","authenticated-orcid":false,"given":"Pengbo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Cardiovascular Hospital (Institute), Shanxi Clinical Medical Research Center for Cardiovascular Disease  Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery The Affiliated Cardiovascular Hospital of Shanxi Medical University, Shanxi Cardiovascular Hospital (Institute), Shanxi Clinical Medical Research Center for Cardiovascular Disease  Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"issue":"8","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nrm1983","article-title":"Regulation of Cardiac Hypertrophy by Intracellular Signalling Pathways","volume":"7","author":"Heineke J.","year":"2006","journal-title":"Nature Reviews. 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