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Saikosaponin D, a plant widely used in traditional Chinese medicine for treating inflammation, fever, and liver diseases. This research was intended to elucidate the function and mechanism of Saikosaponin D (SSD) in ameliorating liver ischemia\u2013reperfusion injury. The effect of SSD on liver ischaemia\u2010reperfusion injury was studied in mice following oral gavage administration. Liver injury was assessed using haematoxylin and eosin (H&amp;E) staining and serum biochemical analysis. To evaluate ferroptosis levels, various methods were used, including reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) and oxidized glutathione (GSSG) levels, Malondialdehyde (MDA), Fe\n                    <jats:sup>2+<\/jats:sup>\n                    indicator FerroOrange, Western blotting and transmission electron microscopy (TEM). The effect of Saikosaponin D in combination with signal transducer and activator of transcription 3 (STAT3) overexpression or PTEN\u2010induced putative kinase 1 (PINK1) knockdown on ferroptosis in a hypoxia\u2013reoxygenation model was studied in\u00a0vitro. SSD alleviated liver ischemia\u2013reperfusion injury by activating mitophagy and inhibiting ferroptosis. The mitochondrial autophagy inhibitor Mdivi\u20101 reversed the pharmacodynamic effects of SSD. Importantly, in hypoxia\u2010reoxygenation of AML12 cells, STAT3 overexpression inhibited PINK1\u2010associated mitophagy, aggravated Fe\n                    <jats:sup>2+<\/jats:sup>\n                    accumulation, lipid peroxidation and malondialdehyde levels, accelerated GSH depletion, aggravated the downregulation of Glutathione Peroxidase 4 (GPX4) and Solute carrier family 7 membrane 11 (SLC7A11) and upregulation of Transferrin receptor (TFR), while PINK1 silencing produced similar results. The inhibitory effect of SSD on ferroptosis in a hypoxia\u2010reoxygenation model was counteracted by STAT3 overexpression and PINK1 silencing. SSD protects the liver against ischemia\u2013reperfusion injury by inhibiting ferroptosis through STAT3\/PINK1\/PARKIN\u2010mediated mitophagy, highlighting its potential as a therapeutic agent in liver ischemia\u2013reperfusion injury treatment.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70333","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:30:01Z","timestamp":1776061801000},"page":"3722-3740","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Saikosaponin D Alleviates Liver Ischemia\u2013Reperfusion Injury by Inhibiting Mitophagy\u2010Associated Ferroptosis via the\n                    <scp>STAT3<\/scp>\n                    \/\n                    <scp>PINK1<\/scp>\n                    Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Xingyun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University  Hefei 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