{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:22:18Z","timestamp":1792034538798,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ulcerative colitis (UC), a common inflammatory bowel disease, has become increasingly prevalent worldwide, posing significant health challenges. This study explored the anti\u2010inflammatory effects of \u03b2\u2010sitosterol on UC and its underlying molecular mechanisms. Using a dextran sulfate sodium (DSS)\u2010induced colitis model in male C57BL\/6 mice, the therapeutic potential of \u03b2\u2010sitosterol at low (2\u2009mg\/kg) and high (6\u2009mg\/kg) doses was compared with sulfasalazine (300\u2009mg\/kg) as a positive control. Disease progression was assessed through Disease Activity Index (DAI) scores, histological analysis, and inflammatory marker expression. \u03b2\u2010sitosterol significantly ameliorated colonic inflammation, demonstrated by lower DAI scores, improved histological architecture, and reduced levels of inflammatory mediators, including NO, MPO, IL\u20106, and iNOS, while upregulating the anti\u2010inflammatory cytokine IL\u201010. Mechanistically, \u03b2\u2010sitosterol promoted AMP\u2010activated protein kinase (AMPK) expression and suppressed myosin light chain kinase (MLCK) expression. These findings were validated in vitro using LPS\u2010stimulated Caco\u20102 cells, where \u03b2\u2010sitosterol decreased inflammatory marker levels and modulated AMPK\/MLCK signaling. Notably, the use of Compound C, an AMPK inhibitor, reversed these effects by suppressing AMPK activity and restoring MLCK expression, confirming that the anti\u2010inflammatory actions of \u03b2\u2010sitosterol are AMPK\u2010dependent. In conclusion, this study highlights the therapeutic potential of \u03b2\u2010sitosterol in UC through modulation of the AMPK\/MLCK signaling pathway. These findings not only deepen our understanding of \u03b2\u2010sitosterol's anti\u2010inflammatory properties but also suggest its potential in developing novel AMPK\u2010targeted therapies for inflammatory bowel disease management.<\/jats:p>","DOI":"10.1002\/jbt.70287","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T03:09:27Z","timestamp":1747883367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b2\u2010Sitosterol Ameliorates Ulcerative Colitis Through Modulation of the AMPK\/MLCK Anti\u2010Inflammatory Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Yuansen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxiao","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8583-8875","authenticated-orcid":false,"given":"Sensen","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Affiliated Hospital of Wenzhou Medical University Ruian Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-023-03214-9"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2024.03.028"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929866527666200813204833"},{"key":"e_1_2_10_5_1","first-page":"253","article-title":"Research Progress of Anti\u2010Inflammatory Effects and Molecular Mechanism of Ginsenosides","volume":"54","author":"Liu B.","year":"2019","journal-title":"Chinese Pharmaceutical Journal"},{"key":"e_1_2_10_6_1","first-page":"310","article-title":"Biological Activity and Application of Food\u2010Derived Sterol Components","volume":"40","author":"Jia S.","year":"2019","journal-title":"International Journal of Food Science & Technology"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.21010\/ajtcam.v14i1.13"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.8b04555"},{"key":"e_1_2_10_9_1","first-page":"2811","article-title":"Effect of \u03b2\u2010sitosterol on Inflammation in Mice With Helicobacter Pylori Infectious Gastritis","volume":"38","author":"Chen T. 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