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Reducing cholesterol burden is important to prevent\/treat gallstone. In this study, we investigated the application of diosgenin (DG) to prevent the formation of gallstone in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adult male C57BL\/6J mice were fed with the lithogenic diet (LD) only or LD supplemented with DG or ezetimibe for 8\u00a0weeks. Incidences of gallstone formation were documented. Intestine and liver tissues were collected to measure the lipid contents and expression of genes in cholesterol metabolism. Caco2 cells were treated with DG to monitor the regulation on cholesterol absorption and the transcriptional regulation of\n                      <jats:italic>Npc1l1<\/jats:italic>\n                      gene. Changes of gut microbiota by DG was analyzed. Intraperitoneal injection of LPS on mice was performed to verify its effects on STAT3 activation and\n                      <jats:italic>Npc1l1<\/jats:italic>\n                      expression in the small intestine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LD led to 100% formation of gallstones in mice. In comparison, dietary DG or ezetimibe supplementary completely prevents gallstones formation. DG inhibited intestinal cholesterol absorption in mice as well as in Caco2 cells by down-regulation of\n                      <jats:italic>Npc1l1<\/jats:italic>\n                      expression. DG could directly inhibit phosphorylation of STAT3 and its transcriptional regulation of\n                      <jats:italic>Npc1l1<\/jats:italic>\n                      expression. Furthermore, DG could modulate gut microbiota profiles and LPS mediated STAT3 activation and\n                      <jats:italic>Npc1l1<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results demonstrated that dietary DG could inhibit intestinal cholesterol absorption through decreasing NPC1L1 expression to prevent cholesterol gallstone formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-023-00933-3","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T02:02:33Z","timestamp":1687831353000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dietary diosgenin transcriptionally down-regulated intestinal NPC1L1 expression to prevent cholesterol gallstone formation in mice"],"prefix":"10.1186","volume":"30","author":[{"given":"Weiyi","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"issue":"1","key":"933_CR1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.jhep.2016.03.005","volume":"65","author":"European Association for the Study of the Liver","year":"2016","unstructured":"European Association for the Study of the Liver. 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