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Geniposide (GE) has anti\u2010inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC) for 4\u2009weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro\u2010inflammatory (IL\u20106, VCAM\u20101, MCP\u20101, and F4\/80) and profibrogenic markers (Col1\u03b11, Col1\u03b12, TGF\u2010\u03b2, and \u03b1\u2010SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC\u2010fed mice, suggesting that GE could ameliorate DDC\u2010induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR\u2010FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC\u2010fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.<\/jats:p>","DOI":"10.1002\/ptr.7086","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T06:33:13Z","timestamp":1616653993000},"page":"3799-3811","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Geniposide suppresses liver injury in a mouse model of <scp>DDC<\/scp>\u2010induced sclerosing cholangitis"],"prefix":"10.1002","volume":"35","author":[{"given":"Min","family":"Wen","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Pharmacy China Pharmaceutical University  Nanjing P.R. 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