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Up to now, no evidence has shown that acute respiratory distress syndrome (ARDS) is improved by liriodendrin. This study was conducted to investigate the protective effects of liriodendrin against oxidative stress and ferroptosis, key mechanisms underlying the pathogenesis of ARDS, in a mouse model of lipopolysaccharide (LPS)\u2010induced ARDS. To investigate the potential of liriodendrin to mitigate oxidative stress and inhibit ferroptosis, adult BALB\/c male mice with LPS\u2010induced ARDS were treated with varying concentrations of liriodendrin. Mice received liriodendrin or dexamethasone before LPS administration. The effects of liriodendrin were evaluated by measuring changes in pulmonary histopathology, levels of lipid peroxidation, activities of antioxidative enzymes (superoxide dismutase, catalase, glutathione peroxidase), and expression of ferroptosis\u2010related proteins (heme oxygenase\u20101, cystine\/glutamate antiporter SLC7A11, glutathione peroxidase\u20104). In addition, we measured the phosphorylation of nuclear factor erythroid 2\u2010related factor 2 (Nrf\u20102), a critical regulator of cellular defense mechanisms against oxidative damage. The results indicated that liriodendrin substantially suppressed histopathological damage, reduced lipid peroxidation, and restored antioxidative enzyme activity in a dose\u2010dependent manner. Furthermore, this compound markedly upregulated the expression of ferroptosis\u2010related proteins and promoted the phosphorylation of Nrf\u20102. Our findings suggest that liriodendrin protects against LPS\u2010induced ARDS by regulating oxidative stress and ferroptosis. The ability of liriodendrin to modulate both antioxidative responses and ferroptosis markers through Nrf\u20102 phosphorylation highlights its potential as a therapeutic agent in the treatment of ARDS.<\/jats:p>","DOI":"10.1002\/tox.24565","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T11:09:45Z","timestamp":1756292985000},"page":"131-140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protective Effects of Liriodendrin Against Oxidative Stress and Ferroptosis in a Mouse Model of Lipopolysaccharide\u2010Induced Acute Respiratory Distress Syndrome"],"prefix":"10.1002","volume":"41","author":[{"given":"Frank Cheau\u2010Feng","family":"Lin","sequence":"first","affiliation":[{"name":"School of Medicine, Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Thoracic Surgery Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"Department of Parenteral Nutrition Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng\u2010Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"Department of Internal Medicine School of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Pin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine, Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Internal Medicine Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Hung","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine, Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Internal Medicine Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella Chin\u2010Shaw","family":"Tsai","sequence":"additional","affiliation":[{"name":"Superintendent Office, Tungs' Taichung MetroHarbor Hospital  Taichung Taiwan"},{"name":"Department of Post\u2010Baccalaureate Medicine College of Medicine, National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-6394","authenticated-orcid":false,"given":"Yu\u2010Hsiang","family":"Kuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Medicine, Chung Shan Medical University  Taichung Taiwan"},{"name":"Department of Pharmacy Chung Shan Medical University Hospital  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/861256"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2014.103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28227663"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2021.1880405"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.09.012"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117342"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113405"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb45080404"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2004.05.015"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111235"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786411003752102"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01369-2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.133427"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155373"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24233"},{"key":"e_1_2_11_17_1","first-page":"3799","article-title":"Protective Effect of Hibifolin on Lipopolysaccharide\u2010Induced Acute Lung Injury Through Akt Phosphorylation and NF\u2010\u03baB Pathway","volume":"39","author":"Ng Y. 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