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Key therapeutic targets were screened using transcriptomics and network pharmacology. Mechanistic validation utilized AAV-mediated lipocalin-2 (LCN2) overexpression, the ferroptosis inhibitor ferrostatin-1 (Fer-1), and the ERK inhibitor PD98059. COL treatment significantly ameliorated pancreatic pathological injury, inflammatory cell infiltration, and cytokine release. LCN2 was identified as a pivotal target markedly upregulated in SAP but downregulated by COL. Crucially, LCN2 overexpression reversed COL\u2019s therapeutic benefits and restored ferroptosis markers (COX2, Fe2+, ROS) while suppressing anti-ferroptotic indices. Notably, this reversal was effectively abrogated by co-treatment with either Fer-1 or PD98059, confirming the involvement of the MAPK\/ERK pathway. This study is the first to elucidate that COL inhibits ferroptosis in pancreatic acinar cells by downregulating LCN2 and subsequently suppressing the LCN2\/MAPK\/ERK signaling axis. These findings provide a novel molecular basis for COL and highlight a potential target for therapeutic intervention in SAP.<\/jats:p>","DOI":"10.4081\/ejh.2026.4557","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T08:51:57Z","timestamp":1778489517000},"source":"Crossref","is-referenced-by-count":0,"title":["Colchicine alleviates severe acute pancreatitis in rats by inhibiting acinar cell ferroptosis &lt;i&gt;via&lt;\/i&gt; LCN2\/MAPK\/ERK signaling axis"],"prefix":"10.4081","volume":"70","author":[{"given":"Liu","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2549","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"50122","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302779"},{"key":"50123","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.20317"},{"key":"50124","doi-asserted-by":"publisher","DOI":"10.1007\/BF02925968"},{"key":"50125","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.14961"},{"key":"50126","doi-asserted-by":"publisher","DOI":"10.1002\/pca.702"},{"key":"50127","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1012510"},{"key":"50128","doi-asserted-by":"publisher","DOI":"10.18502\/ijaai.v24i4.19134"},{"key":"50129","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.12.027"},{"key":"50130","doi-asserted-by":"publisher","DOI":"10.34133\/bmr.0089"},{"key":"50131","doi-asserted-by":"publisher","DOI":"10.18502\/ijaai.v23i2.15326"},{"key":"50132","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-02007-1"},{"key":"50133","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06216-x"},{"key":"50134","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064559"},{"key":"50135","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103342"},{"key":"50136","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2062887"},{"key":"50137","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155968"},{"key":"50138","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2018.3429"},{"key":"50139","doi-asserted-by":"publisher","DOI":"10.3390\/md15020045"},{"key":"50140","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2009970"},{"key":"50141","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2014.00117"},{"key":"50142","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2015.06.013"},{"key":"50143","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3394"},{"key":"50144","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-07-0405"},{"key":"50145","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(00)00148-5"},{"key":"50146","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.09.018"},{"key":"50147","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142351"},{"key":"50148","unstructured":"27. 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