{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:25:12Z","timestamp":1786965912638,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with limited effectiveness and safety of current drug therapies. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid present in traditional Chinese medicines used clinically as retention enemas for UC, but its direct effects and mechanisms remain unclear. This study evaluated the therapeutic impact of BA enema in dextran sulfate sodium (DSS)\u2010induced colitis by monitoring disease activity index (DAI), colon length, and histopathology, and by assessing inflammatory cytokines, mucosal tight junction, and mucin\u20102 (MUC2) expression. Colonic mucosa\u2010associated microbiota were profiled by 16S rRNA gene sequencing. Potential BA targets were predicted using Swiss Target Prediction and validated by molecular docking, molecular dynamics simulations, cellular thermal shift assay, and biolayer interferometry. The functional relevance of the vitamin D receptor (VDR) was examined using a VDR antagonist in\u00a0vivo and in\u00a0vitro, and transcriptomic datasets from UC patients were analyzed to define VDR expression patterns. BA enema markedly attenuated DSS\u2010induced colitis, such as reducing the DAI, inhibiting colonic damage, and improving colon length shortening. The BA also significantly restored the tight junction proteins, associated mucin proteins, and mucin\u20102 (MUC2). The BA reduced potentially pathogenic bacteria in the colonic mucosa. In addition, BA significantly restored the VDR proteins, and the VDR antagonist weakened the effects of BA in\u00a0vivo and in\u00a0vitro. The binding site between VDR and BA was Trp286. Transcriptomic analyses confirmed VDR downregulation in UC. These findings indicate that BA enema alleviates experimental colitis in part by targeting VDR to protect the intestinal mucosal barrier and modulate mucosa\u2010associated microbiota, supporting BA as a promising candidate for UC treatment.<\/jats:p>","DOI":"10.1002\/ptr.70404","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:34:12Z","timestamp":1781843652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Betulinic Acid Enema Alleviates Colitis by Targeting Vitamin D Receptor to Protect the Intestinal Mucosal Barrier and Modulate Mucosa\u2010Associated Microbiota"],"prefix":"10.1002","author":[{"given":"Lina","family":"Dong","sequence":"first","affiliation":[{"name":"Core Laboratory, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University  Taiyuan Shanxi People's Republic of China"},{"name":"Department of Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxia","family":"Gao","sequence":"additional","affiliation":[{"name":"Core Laboratory, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University  Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Core Laboratory, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University  Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences, Shanxi University  Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University  Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University  Taiyuan Shanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03227-20"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010012"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.455"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000051"},{"key":"e_1_2_13_6_1","first-page":"238","article-title":"Clinicopathologic Study of Dextran Sulfate Sodium Experimental Murine Colitis","volume":"69","author":"Cooper H. 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