{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:58:40Z","timestamp":1788260320887,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ulcerative colitis (UC), a chronic inflammatory bowel disorder with no clear etiology, causes diverse complications and severely impairs patients' quality of life. Lipocalin\u20102 (LCN2) is recognized as a potential fecal biomarker for UC. Brusatol (BR), a quassinoid compound isolated from\n                    <jats:italic>Brucea javanica<\/jats:italic>\n                    , has exhibited anti\u2010inflammatory and therapeutic effects in preclinical studies. While BR inhibits UC progression, its specific molecular mechanisms remain to be elucidated. An in\u00a0vitro cell model of UC was constructed by treating human normal colorectal mucosal cells (FHC) with tumor necrosis factor\u2010alpha (TNF\u2010\u03b1). Cell viability and apoptosis were assessed using CCK\u20108, 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine (EdU) and flow cytometry. Additionally, inflammatory cytokines and ferroptosis\u2010related factors were analyzed using corresponding kits. Western blot and qRT\u2010PCR were conducted for protein and mRNA detection. Bioinformatics analysis and co\u2010immunoprecipitation (Co\u2010IP) assay were employed to investigate the relationship between LCN2 and ubiquitin protein ligase E3A (UBE3A). Finally, in\u00a0vivo UC models were established, followed by BR treatment and evaluation of colon pathological changes and target molecule expression. In the TNF\u2010\u03b1\u2010induced FHC cell injury model, BR significantly suppressed cell injury and ferroptosis, and this effect was associated with downregulating LCN2 expression. The ubiquitin ligase UBE3A negatively regulated LCN2 expression. The protective effect of UBE3A overexpression against TNF\u2010\u03b1\u2010induced damage was abolished by LCN2 upregulation. BR alleviated cell injury by upregulating UBE3A expression, which in turn inhibited LCN2 expression. In the UC mouse model, BR mitigated colonic pathological damage, downregulated LCN2 expression, and upregulated UBE3A levels. BR exerted anti\u2010colitis effects by upregulating the expression of UBE3A and downregulating LCN2 levels, thereby inhibiting cell injury, ferroptosis, and colonic pathological damage.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70201","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T11:58:16Z","timestamp":1765195096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Brusatol Exerts Therapeutic Effects in Ulcerative Colitis by Regulating the\n                    <scp>UBE<\/scp>\n                    3\n                    <scp>A<\/scp>\n                    \u2010\n                    <scp>LCN<\/scp>\n                    2\u2010Mediated Ferroptosis and Inflammation Axis"],"prefix":"10.1111","volume":"106","author":[{"given":"Xingzhuo","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Beihua University  Jilin Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Beihua University  Jilin Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5008-0219","authenticated-orcid":false,"given":"Zhiping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Beihua University  Jilin Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Beihua University  Jilin Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingze","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Beihua University  Jilin Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hospital of Beihua University  Jilin Jilin Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-1032","authenticated-orcid":false,"given":"Hongjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The People's Hospital of Suzhou New District  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.79915"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106276"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/jir.s501651"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180820666230516160527"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2023.199191"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1317620"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3881\/j.issn.1000\u2010503X.15918"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010025\u201003629\u20100"},{"key":"e_1_2_10_10_1","first-page":"238","article-title":"Clinicopathologic Study of Dextran Sulfate Sodium Experimental Murine Colitis","volume":"69","author":"Cooper H. 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