{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:52:01Z","timestamp":1791445921443,"version":"4.3.3"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background and Aims:<\/jats:bold> Therapeutic drugs that are used to treat cholestatic liver disease are limited; however, the results of clinical trials on primary biliary cholangitis treatment targeting peroxisome proliferator-activated receptors (PPARs) are encouraging. In this study, we aimed to identify the effects of MBT1805, a novel balanced PPAR\u03b1\/\u03b3\/\u03b4 agonist, on cholestasis induced by \u03b1-naphthylisothiocyanate (ANIT) and elucidate the underlying mechanisms through untargeted and bile acid-targeted metabolomic analysis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Levels of serum biochemical indicators (transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin) and liver histopathology were analyzed to evaluate the therapeutic effects of MBT1805 on ANIT-induced cholestasis in C57BL\/6 mice. Untargeted and bile acid-targeted metabolomic analysis of liver tissues was performed using ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MC\/MC). qRT-PCR and Western blot analysis were carried out to measure the expression of key enzymes and transporters regulating bile acid synthesis, biotransformation, and transport.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> MBT1805 significantly improved abnormal levels of liver biochemical indicators and gallbladder enlargement induced by ANIT. Histopathological analysis showed that MBT1805 effectively relieved ANIT-induced necrosis, vacuolation, and inflammatory infiltration. Untargeted metabolomic analysis identified 27 metabolites that were involved in the primary biliary acid biosynthesis pathway. In addition, bile acid-targeted metabolomics showed that MBT1805 could alleviate the abnormal bile acid content and composition induced by ANIT. Furthermore, qRT-PCR and Western blot results confirmed that MBT1805 could effectively regulate bile acid synthesis, biotransformation, and transport which helps relieve cholestasis.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> MBT1805 is a potential candidate drug for cholestasis, with a balanced PPAR\u03b1\/\u03b3\/\u03b4 activation effect.<\/jats:p>","DOI":"10.3389\/fphar.2021.732478","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T05:09:39Z","timestamp":1635484179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolomic Analysis Reveals the Therapeutic Effects of MBT1805, a Novel Pan-Peroxisome Proliferator-Activated Receptor Agonist, on \u03b1-Naphthylisothiocyanate-Induced Cholestasis in Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Chang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohua","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.2741\/539","article-title":"Mitochondrial Dysfunction in Cholestatic Liver Diseases","volume":"4","author":"Arduini","year":"2012","journal-title":"Front. 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