{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:03:04Z","timestamp":1790290984379,"version":"4.1.0"},"reference-count":136,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H02928"],"award-info":[{"award-number":["20H02928"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K14813"],"award-info":[{"award-number":["21K14813"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["The JSPS Core-to-Core Program A (Advanced Research Network) entitled \u201cEstablishment of in-ternational agricultural immunology research-core for quantum improvement in food safety\u201d"],"award-info":[{"award-number":["The JSPS Core-to-Core Program A (Advanced Research Network) entitled \u201cEstablishment of in-ternational agricultural immunology research-core for quantum improvement in food safety\u201d"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK1 may reduce the risk of death in patients with chronic liver failure. VK deficiency is associated with intrahepatic cholestasis, and is already being used as a drug for cholestasis-induced liver fibrosis in China. In Japan, to treat osteoporosis in patients with primary biliary cholangitis, VK2 formulations are prescribed, along with vitamin D3. Animal studies have revealed that after bile duct ligation-induced cholestasis, PXR knockout mice manifested more hepatic damage than wild-type mice. Ligand-mediated activation of PXR improves biochemical parameters. Rifampicin is a well-known human PXR ligand that has been used to treat intractable pruritus in severe cholestasis. In addition to its anti-cholestatic properties, PXR has anti-fibrotic and anti-inflammatory effects. However, because of the scarcity of animal studies, the mechanism of the effect of VK on cholestasis-related liver disease has not yet been revealed. Moreover, the application of VK in cholestasis-related diseases is controversial. Considering this background, the present review focuses on the effect of VK in cholestasis-related diseases, emphasizing its function as a modulator of PXR.<\/jats:p>","DOI":"10.3390\/nu13082515","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T10:31:44Z","timestamp":1627036304000},"page":"2515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The Role of Vitamin K in Cholestatic Liver Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Halima","family":"Sultana","sequence":"first","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Komai","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-5274","authenticated-orcid":false,"given":"Hitoshi","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, Japan"},{"name":"International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1111\/j.1538-7836.2005.01419.x","article-title":"The vitamin K cycle","volume":"3","author":"Stafford","year":"2005","journal-title":"J. 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