{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:32:03Z","timestamp":1792794723144,"version":"4.5.0"},"reference-count":33,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81760678"],"award-info":[{"award-number":["81760678"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.taap.2025.117277","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:15:39Z","timestamp":1740010539000},"page":"117277","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Hepatotoxicity from long-term administration of hepatoprotective low doses of oleanolic acid in mice"],"prefix":"10.1016","volume":"497","author":[{"given":"Yasha","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2025.117277_bb0005","doi-asserted-by":"crossref","DOI":"10.1177\/1534735419869479","article-title":"Literature review of traditional Chinese medicine herbs-induced liver injury from an oncological perspective with RUCAM","volume":"18","author":"Chow","year":"2019","journal-title":"Integr. Cancer Ther."},{"key":"10.1016\/j.taap.2025.117277_bb0010","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1056\/NEJMoa1306033","article-title":"Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease","volume":"369","author":"de Zeeuw","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.taap.2025.117277_bb0015","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/1308749","article-title":"Development and evaluation of Oleanolic acid dosage forms and its derivatives","volume":"2020","author":"Feng","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.taap.2025.117277_bb0020","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3389\/fphar.2020.00747","article-title":"LC-MS-based Metabolomic study of Oleanolic acid-induced hepatotoxicity in mice","volume":"11","author":"Feng","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0025","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/jat.4298","article-title":"Farnesoid X receptor contributes to oleanolic acid-induced cholestatic liver injury in mice","volume":"42","author":"Feng","year":"2022","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.taap.2025.117277_bb0030","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s11901-018-0411-0","article-title":"Long-term outcomes after drug-induced liver injury","volume":"17","author":"Hayashi","year":"2018","journal-title":"Curr. Hepatol. Rep."},{"key":"10.1016\/j.taap.2025.117277_bb0035","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Hernandez-Gea","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.taap.2025.117277_bb0040","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1002\/jat.4456","article-title":"AMP-activated protein kinase-farnesoid X receptor pathway contributes to oleanolic acid-induced liver injury","volume":"43","author":"Huang","year":"2023","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.taap.2025.117277_bb0045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-pharmtox-011112-140312","article-title":"Learning to program the liver","volume":"54","author":"Klaassen","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.taap.2025.117277_bb0050","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.taap.2010.01.013","article-title":"Nrf2 the rescue: effects of the antioxidative\/electrophilic response on the liver","volume":"244","author":"Klaassen","year":"2010","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0055","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s40265-023-01874-9","article-title":"Omaveloxolone: first approval","volume":"83","author":"Lee","year":"2023","journal-title":"Drugs"},{"key":"10.1016\/j.taap.2025.117277_bb0060","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/bmc.3577","article-title":"A rapid UPLC-MS\/MS method for the determination of oleanolic acid in rat plasma and liver tissue: application to plasma and liver pharmacokinetics","volume":"30","author":"Li","year":"2016","journal-title":"Biomed. Chromatogr."},{"key":"10.1016\/j.taap.2025.117277_bb0065","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.phymed.2018.09.174","article-title":"A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins","volume":"50","author":"Li","year":"2018","journal-title":"Phytomedicine"},{"key":"10.1016\/j.taap.2025.117277_bb0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2023.116509","article-title":"Suppression of SIRT1\/FXR signaling pathway contributes to oleanolic acid-induced liver injury","volume":"467","author":"Liao","year":"2023","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0075","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.taap.2013.08.003","article-title":"Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice","volume":"272","author":"Liu","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0080","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/liv.13940","article-title":"Oleanolic acid reprograms the liver to protect against hepatotoxicants, but is hepatotoxic at high doses","volume":"39","author":"Liu","year":"2019","journal-title":"Liver Int."},{"key":"10.1016\/j.taap.2025.117277_bb0085","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.3390\/molecules18033060","article-title":"Repeated oral administration of oleanolic acid produces cholestatic liver injury in mice","volume":"18","author":"Lu","year":"2013","journal-title":"Molecules"},{"key":"10.1016\/j.taap.2025.117277_bb0090","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1002\/ana.25934","article-title":"Safety and efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe study)","volume":"89","author":"Lynch","year":"2021","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.taap.2025.117277_bb0095","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/978-3-319-41342-6_13","article-title":"CDDO and its role in chronic diseases","volume":"929","author":"Mathis","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.taap.2025.117277_bb0100","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.phytochem.2011.12.022","article-title":"Oleanolic acid","volume":"77","author":"Pollier","year":"2012","journal-title":"Phytochemistry"},{"key":"10.1016\/j.taap.2025.117277_bb0105","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.bcp.2008.12.028","article-title":"Oleanolic acid activates Nrf2 and protects from acetaminophen hepatotoxicity via Nrf2-dependent and Nrf2-independent processes","volume":"77","author":"Reisman","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0110","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/10408440601177863","article-title":"A review of the hepatotoxic plant Lantana camara","volume":"37","author":"Sharma","year":"2007","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.taap.2025.117277_bb0115","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/apt.12798","article-title":"Review article: Herbal hepatotoxicity--an update on traditional Chinese medicine preparations","volume":"40","author":"Teschke","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.taap.2025.117277_bb0120","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. Biol."},{"key":"10.1016\/j.taap.2025.117277_bb0125","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.1007\/s00210-024-02959-2","article-title":"Therapeutic potential of oleanolic acid in liver diseases","volume":"397","author":"Wang","year":"2024","journal-title":"Naunyn Schmiedeberg's Arch. Pharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0130","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/17474124.2018.1427581","article-title":"Clinical characteristics and outcomes of traditional Chinese medicine-induced liver injury: a systematic review","volume":"12","author":"Wang","year":"2018","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.taap.2025.117277_bb0135","doi-asserted-by":"crossref","DOI":"10.3390\/ijms18030553","article-title":"A new Oleanolic acid derivative against CCl\u2084-induced hepatic fibrosis in rats","volume":"18","author":"Xiang","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.taap.2025.117277_bb0140","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-\u03b2\/SMAD pathway and its regulation in hepatic fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"10.1016\/j.taap.2025.117277_bb0145","article-title":"Radix Bupleuri: a review of traditional uses, botany, phytochemistry, pharmacology, and toxicology","volume":"2017","author":"Yang","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"10.1016\/j.taap.2025.117277_bb0150","doi-asserted-by":"crossref","first-page":"7697","DOI":"10.1021\/jf302529x","article-title":"Bioavailability, distribution, and antioxidative effects of selected triterpenes in mice","volume":"60","author":"Yin","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.taap.2025.117277_bb0155","article-title":"Sophorae tonkinensis radix et rhizoma: a comprehensive review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, toxicology and detoxification strategy","volume":"337","author":"Zeng","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.taap.2025.117277_bb0160","article-title":"Oleanolic acid attenuates renal fibrosis through TGF-\u03b2\/Smad pathway in a rat model of unilateral ureteral obstruction","volume":"2020","author":"Zhao","year":"2020","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"10.1016\/j.taap.2025.117277_bb0165","doi-asserted-by":"crossref","first-page":"F808","DOI":"10.1152\/ajprenal.00376.2012","article-title":"Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects","volume":"304","author":"Zoja","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X25000535?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X25000535?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T05:25:47Z","timestamp":1741584347000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X25000535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":33,"alternative-id":["S0041008X25000535"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2025.117277","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepatotoxicity from long-term administration of hepatoprotective low doses of oleanolic acid in mice","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2025.117277","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117277"}}