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Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of <jats:italic>Polygonum cuspidatum<\/jats:italic>, which has anti\u2010inflammatory, anti\u2010tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6\u2010trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti\u2010colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.<\/jats:p>","DOI":"10.1002\/ptr.7533","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T10:31:03Z","timestamp":1656498663000},"page":"3662-3671","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Polydatin alleviates <scp>DSS\u2010<\/scp> and <scp>TNBS<\/scp>\u2010induced colitis by suppressing Th17 cell differentiation via directly inhibiting <scp>STAT3<\/scp>"],"prefix":"10.1002","volume":"36","author":[{"given":"Yao\u2010Jun","family":"Liu","sequence":"first","affiliation":[{"name":"College of Pharmacy Fujian University of Traditional Chinese Medicine  Fuzhou P.R. 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