{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:58:38Z","timestamp":1789167518841,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Sector, Kuwait University","award":["YM 10\/20"],"award-info":[{"award-number":["YM 10\/20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn\u2019s disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin. Methods: Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days. Animals were treated daily with nobiletin [oral, 60 mg\/Kg body weight] and studied in four groups, C [non-colitis control], D [DSS-induced colitis], CN [nobiletin-treated non-colitis control], and DN [nobiletin-treated DSS-induced colitis]. On day seven, the animals were sacrificed, and colonic tissues were collected and analyzed. Results: Both macroscopic and microscopic findings suggest the progression of colitis. In the inflamed colon, claudin-1 and -4 proteins were decreased, claudin-2 increased, while the claudin-3 protein remained unchanged. Except for claudin-1, these changes were not paralleled by mRNA expression, indicating a complex regulatory mechanism. Uniform \u03b2-actin expression along with consistent quality and yield of total RNA indicated selectivity of these changes. Nobiletin treatment reversed these changes. Conclusions: Altered expression of the claudin isoforms -1, -2, and -4 disrupts tight junctions, exposing the lamina propria to microflora, leading to electrolyte disturbance and the development of ulcerative colitis. Nobiletin with its anti-inflammatory properties may be useful in IBD.<\/jats:p>","DOI":"10.3390\/biom14091122","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T02:34:06Z","timestamp":1725503646000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin"],"prefix":"10.3390","volume":"14","author":[{"given":"Asmaa","family":"Al-Failakawi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishah","family":"Al-Jarallah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8815-2089","authenticated-orcid":false,"given":"Muddanna","family":"Rao","sequence":"additional","affiliation":[{"name":"Departments of Anatomy, College of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: A therapeutic target?","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. Rev. Gastroenterol. 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