{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:21:19Z","timestamp":1783408879172,"version":"3.54.6"},"reference-count":46,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["No. RS-2024-00465177"],"award-info":[{"award-number":["No. RS-2024-00465177"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Citrinin (CTN), a mycotoxin commonly found in contaminated food and animal feed, impairs intestinal barrier integrity through oxidative stress and cytotoxicity. However, its link to ferroptosis, an iron-dependent form of regulated cell death, remains unclear. This study investigated whether CTN induces ferroptosis in intestinal epithelial cells and evaluated the protective role of Euphorbia hypericifolia (EH) against CTN-induced oxidative damage and tight junction (TJ) disruption. Using IPEC-J2 cells exposed to CTN, intracellular ferrous ion (Fe2+) levels, reactive oxygen species (ROS) accumulation, and TJ integrity were assessed using FerroOrange and DCFH-DA staining, RT-qPCR, immunofluorescence, and WST-1 assays. Additionally, a high-throughput screen of 459 natural products identified EH extract as a top candidate in mitigating CTN toxicity. The CTN treatment significantly elevated intracellular Fe2+ and ROS levels, downregulated antioxidant genes (notably CAT), and disrupted ZO-1 expression and TJ morphology in IPEC-J2 cells, all hallmarks of ferroptosis-like cell death. Co-treatment with EH extract effectively reversed these effects, restoring antioxidant gene expression, reducing Fe2+ and ROS accumulation, and preserving TJ structure. Phytochemical profiling of EH extract revealed several bioactive compounds potentially responsible for its protective effects. These findings suggest that CTN induces ferroptosis-related cytotoxicity in IPEC-J2 cells, but EH alleviates this toxicity by modulating oxidative stress and iron homeostasis, supporting its potential use as a natural feed additive for intestinal protection<\/jats:p>","DOI":"10.3390\/ijms26167773","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T07:53:44Z","timestamp":1754985224000},"page":"7773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Euphorbia hypericifolia Attenuates Citrinin-Induced Oxidative Stress and Maintains Tight Junction Integrity in Porcine Intestinal Epithelial Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3748-548X","authenticated-orcid":false,"given":"Seung Joon","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Animal Science and Biotechnology, Kyungpook National University, Sangju 37224, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangsu","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Animal Science and Biotechnology, Kyungpook National University, Sangju 37224, Republic of Korea"},{"name":"Research Institute for Innovative Animal Science, Kyungpook National University, Sangju 37224, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Animal Science, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang In","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Animal Science and Biotechnology, Kyungpook National University, Sangju 37224, Republic of Korea"},{"name":"Research Institute for Innovative Animal Science, Kyungpook National University, Sangju 37224, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/bs.afnr.2019.02.007","article-title":"Mycotoxins in food and feed","volume":"89","author":"Pleadin","year":"2019","journal-title":"Adv. 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