{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T20:28:18Z","timestamp":1769545698270,"version":"3.49.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Wuji Wan (WJW) is a classical Chinese formula traditionally prescribed for diarrhea\/dysentery and abdominal pain. In ulcerative colitis (UC), inflammatory diarrhea reflects not only mucosal inflammation but also inflammation-linked disruption of epithelial electrolyte and water handling, highlighting membrane transport as a mechanistic bridge between symptom burden and immune activation. However, it remains unclear whether WJW confers therapeutic benefit in UC and whether any benefit is accompanied by coordinated regulation of membrane-transport\u2013linked pathways. This study therefore asked whether WJW shows therapeutic effects in a UC model and whether these effects are accompanied by changes in epithelial Na\n                      <jats:sup>+<\/jats:sup>\n                      \/Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      transport and water-channel programs and by modulation of the T-cell\u2013linked potassium channel Kv1.3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated this question in a mouse model of DSS-induced colitis (3% dextran sulfate sodium). Our assessment included disease activity index (DAI) scores, histopathological analysis, ELISA, Western blotting, untargeted metabolomics, and whole-cell patch-clamp electrophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WJW significantly ameliorated DSS-induced colitis, as reflected by improved colonic pathology and partial normalization of DSS-associated serum metabolic perturbations. Untargeted metabolomics highlighted transport-related pathways. WJW increased\/normalized the expression of key epithelial transport proteins involved in Na\n                      <jats:sup>+<\/jats:sup>\n                      \/Cl\n                      <jats:sup>\u2212<\/jats:sup>\n                      absorption and water handling, including sodium\/hydrogen exchanger 3 (NHE3), epithelial sodium channel (ENaC), downregulated in adenoma (DRA), aquaporin-3 (AQP3), and aquaporin-8 (AQP8). In parallel, WJW reduced IL-6, IL-17A, and IFN-\u03b3 and dampened ERK\/NF-\u03baB pathway activation. WJW also reduced colonic Kv1.3 protein expression, and WJW-containing plasma directly inhibited Kv1.3 currents in Jurkat T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WJW ameliorated DSS-induced colitis and was accompanied by coordinated modulation of epithelial and immune membrane-transport\u2013linked readouts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1718919","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T06:40:47Z","timestamp":1769496047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Wuji Wan ameliorates ulcerative colitis by restoring impaired membrane transport"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Experimental Research Center, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaogang","family":"Weng","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihao","family":"Deng","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/nri1330","article-title":"Jurkat T cells and development of the T-cell receptor signalling paradigm","volume":"4","author":"Abraham","year":"2004","journal-title":"Nat. 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