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The pathogenesis is mainly caused by 3-monoglucuronyl glycyrrhetinic acid (3MGA), one of the metabolites of glycyrrhizin (GL) contained in licorice. We developed an anti-3MGA monoclonal antibody (MAb) and an ELISA system to easily detect 3MGA in the plasma and urine of the patients. However, we found that some metabolites of GL cross-reacted with this MAb. Mrp2-deficient Eisai Hyperbilirubinemia rats (EHBRs) were administered glycyrrhetinic acid (GA), and we isolated 22<jats:italic>\u03b1<\/jats:italic>-hydroxy-18<jats:italic>\u03b2<\/jats:italic>-glycyrrhetyl-3-<jats:italic>O<\/jats:italic>-sulfate-30-glucuronide (<jats:bold>1<\/jats:bold>) from the pooled urine with the guidance of positive immunostaining of eastern blot as the new metabolite of GL. The IC<jats:sub>50<\/jats:sub> of <jats:bold>1<\/jats:bold> for type 2 11\u03b2-hydroxysteroid dehydrogenase (11<jats:italic>\u03b2<\/jats:italic>-HSD2) was 2.0\u2009\u00b5M. Similar plasma concentrations of <jats:bold>1<\/jats:bold> and GA were observed 12\u2009h after oral administration of GA to EHBR. Compound <jats:bold>1<\/jats:bold> was eliminated via urine, whereas GA was not. In Sprague\u2013Dawley (SD) rats orally treated with GA, compound <jats:bold>1<\/jats:bold> was absent from both the plasma and the urine. Compound <jats:bold>1<\/jats:bold> was actively transported into cells <jats:italic>via<\/jats:italic> OAT1 and OAT3, whereas GA was not. Compound <jats:bold>1<\/jats:bold>, when produced in Mrp2-deficiency, represents a potential causative agent of pseudoaldosteronism, and might be used as a biomarker to prevent the adverse effect.<\/jats:p>","DOI":"10.1038\/s41598-018-33834-9","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T10:14:20Z","timestamp":1539684860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Isolation of a novel glycyrrhizin metabolite as a causal candidate compound for pseudoaldosteronism"],"prefix":"10.1038","volume":"8","author":[{"given":"Osamu","family":"Morinaga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2048-7592","authenticated-orcid":false,"given":"Kan\u2019ichiro","family":"Ishiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ohkita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanting","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Hirasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaki","family":"Mitamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Maki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Yasujima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Yuasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2524-8745","authenticated-orcid":false,"given":"Toshiaki","family":"Makino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,22]]},"reference":[{"key":"33834_CR1","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1002\/(SICI)1097-0142(19970415)79:8<1494::AID-CNCR8>3.0.CO;2-B","volume":"79","author":"Y Arase","year":"1997","unstructured":"Arase, Y. et al. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 79, 1494\u20131500 (1997).","journal-title":"Cancer"},{"key":"33834_CR2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1046\/j.1365-2036.1998.00309.x","volume":"12","author":"TG van Rossum","year":"1998","unstructured":"van Rossum, T. G., Vulto, A. G., de Man, R. A., Brouwer, J. T. & Schalm, S. W. Review article: glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther 12, 199\u2013205 (1998).","journal-title":"Aliment Pharmacol Ther"},{"key":"33834_CR3","doi-asserted-by":"publisher","first-page":"S94","DOI":"10.1159\/000048283","volume":"62","author":"H Kumada","year":"2002","unstructured":"Kumada, H. Long-term treatment of chronic hepatitis C with glycyrrhizin [stronger neo-minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. 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