{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:48:43Z","timestamp":1792702123304,"version":"4.5.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"publisher","award":["2020-JYB-ZDGG-035"],"award-info":[{"award-number":["2020-JYB-ZDGG-035"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204753"],"award-info":[{"award-number":["82204753"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicon"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.toxicon.2025.108366","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T08:24:52Z","timestamp":1744878292000},"page":"108366","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["The DHCR7 is the key target of lipotoxic liver injury caused by matrine through abnormal activation of the cholesterol synthesis pathway"],"prefix":"10.1016","volume":"260","author":[{"given":"Xiaoyu","family":"Tao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linzhen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-6110","authenticated-orcid":false,"given":"Jiarui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongjun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxicon.2025.108366_bib1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"10.1016\/j.toxicon.2025.108366_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2022.102569","article-title":"Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress","volume":"59","author":"Abulikemu","year":"2023","journal-title":"Redox Biol."},{"key":"10.1016\/j.toxicon.2025.108366_bib3","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.042549","article-title":"Zebrafish models of skeletal dysplasia induced by cholesterol biosynthesis deficiency","volume":"13","author":"Anderson","year":"2020","journal-title":"Dis Model Mech"},{"key":"10.1016\/j.toxicon.2025.108366_bib4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-019-0105-0","article-title":"Drug-induced liver injury","volume":"5","author":"Andrade","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.toxicon.2025.108366_bib5","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.1073\/pnas.1419799112","article-title":"Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials","volume":"112","author":"Autefage","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.toxicon.2025.108366_bib6","first-page":"2439","article-title":"[Pharmacological effect and toxicology of Sophorae Tonkinensis Radix et Rhizoma]","volume":"42","author":"Chen","year":"2017","journal-title":"Zhongguo Zhongyao Zazhi"},{"key":"10.1016\/j.toxicon.2025.108366_bib7","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.569530","article-title":"Matrine inhibits CNS autoimmunity through an IFN-\u03b2-Dependent mechanism","volume":"11","author":"Chu","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.toxicon.2025.108366_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118385","article-title":"Beneficial effects of oxymatrine from Sophora flavescens on alleviating Ulcerative colitis by improving inflammation and ferroptosis","volume":"332","author":"Gao","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.toxicon.2025.108366_bib9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s12967-018-1685-2","article-title":"Matrine attenuates endoplasmic reticulum stress and mitochondrion dysfunction in nonalcoholic fatty liver disease by regulating SERCA pathway","volume":"16","author":"Gao","year":"2018","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.toxicon.2025.108366_bib10","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1186\/s12967-019-2020-2","article-title":"Correction to: matrine attenuates endoplasmic reticulum stress and mitochondrion dysfunction in nonalcoholic fatty liver disease by regulating SERCA pathway","volume":"17","author":"Gao","year":"2019","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.toxicon.2025.108366_bib11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.yexmp.2015.06.008","article-title":"Matrine ameliorates experimental autoimmune encephalomyelitis by modulating chemokines and their receptors","volume":"99","author":"Kan","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"10.1016\/j.toxicon.2025.108366_bib12","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types","volume":"114","author":"Klauda","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.toxicon.2025.108366_bib13","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1194\/jlr.M009365","article-title":"Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome","volume":"51","author":"Korade","year":"2010","journal-title":"J. Lipid Res."},{"key":"10.1016\/j.toxicon.2025.108366_bib14","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/hmg\/ddg172","article-title":"Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency","volume":"12","author":"Krakowiak","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.toxicon.2025.108366_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116738","article-title":"Matrine induces autophagic cell death by triggering ROS\/AMPK\/mTOR axis and apoptosis in multiple myeloma","volume":"175","author":"Li","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.toxicon.2025.108366_bib16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jpha.2022.11.005","article-title":"The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2\/HMGCR\/SQLE\/LSS pathway","volume":"13","author":"Li","year":"2023","journal-title":"J Pharm Anal"},{"key":"10.1016\/j.toxicon.2025.108366_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2021.153787","article-title":"Hepatotoxicity induced by PP\u2165 and PP\u2166 in zebrafish were related to the Cholesterol disorder","volume":"95","author":"Li","year":"2022","journal-title":"Phytomedicine"},{"key":"10.1016\/j.toxicon.2025.108366_bib18","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/7150391","article-title":"Research advances on hepatotoxicity of herbal medicines in China","volume":"2016","author":"Liu","year":"2016","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.toxicon.2025.108366_bib19","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1053\/j.gastro.2021.02.051","article-title":"Squalene epoxidase induces nonalcoholic steatohepatitis via binding to carbonic anhydrase III and is a therapeutic target","volume":"160","author":"Liu","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.toxicon.2025.108366_bib20","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1631\/jzus.B1600158","article-title":"Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish","volume":"18","author":"Liu","year":"2017","journal-title":"J. Zhejiang Univ. - Sci. B"},{"key":"10.1016\/j.toxicon.2025.108366_bib21","doi-asserted-by":"crossref","first-page":"8777","DOI":"10.1038\/srep08777","article-title":"Lessons from hepatocyte-specific Cyp51 knockout mice: impaired cholesterol synthesis leads to oval cell-driven liver injury","volume":"5","author":"Lorbek","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.toxicon.2025.108366_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116491","article-title":"Oxymatrine alleviates high-fat diet\/streptozotocin-induced non-alcoholic fatty liver disease in C57BL\/6 J mice by modulating oxidative stress, inflammation and fibrosis","volume":"174","author":"Lou","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.toxicon.2025.108366_bib23","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1089\/ars.2022.0134","article-title":"New insights into herb-induced liver injury","volume":"38","author":"Ma","year":"2023","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.toxicon.2025.108366_bib24","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/15376516.2024.2332613","article-title":"Drug reactive metabolite-induced hepatotoxicity: a comprehensive review","volume":"34","author":"Mahajan","year":"2024","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.toxicon.2025.108366_bib25","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1038\/s41401-018-0016-8","article-title":"Repurposing matrine for the treatment of hepatosteatosis and associated disorders in glucose homeostasis in mice","volume":"39","author":"Mahzari","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.toxicon.2025.108366_bib26","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jsbmb.2016.04.001","article-title":"Genetic disorders of Vitamin D biosynthesis and degradation","volume":"165","author":"Miller","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"10.1016\/j.toxicon.2025.108366_bib27","doi-asserted-by":"crossref","first-page":"14205","DOI":"10.3748\/wjg.v20.i39.14205","article-title":"Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease","volume":"20","author":"Paradies","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.toxicon.2025.108366_bib28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.plipres.2016.09.003","article-title":"DHCR7: a vital enzyme switch between cholesterol and vitamin D production","volume":"64","author":"Prabhu","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"10.1016\/j.toxicon.2025.108366_bib29","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1021\/acs.chemrestox.2c00264","article-title":"Integrative analysis of transcriptomic and metabolomic data for identification of pathways related to matrine-induced hepatotoxicity","volume":"35","author":"Rao","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.toxicon.2025.108366_bib30","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.redox.2016.09.002","article-title":"Effects of dietary fatty acids and cholesterol excess on liver injury: a lipidomic approach","volume":"9","author":"Serviddio","year":"2016","journal-title":"Redox Biol."},{"key":"10.1016\/j.toxicon.2025.108366_bib31","doi-asserted-by":"crossref","DOI":"10.15252\/embr.202152537","article-title":"p53 transcriptionally regulates SQLE to repress cholesterol synthesis and tumor growth","volume":"22","author":"Sun","year":"2021","journal-title":"EMBO Rep."},{"key":"10.1016\/j.toxicon.2025.108366_bib32","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.3748\/wjg.15.2817","article-title":"Drug-induced liver injury: is it somehow foreseeable?","volume":"15","author":"Tarantino","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.toxicon.2025.108366_bib33","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/10408440590935620","article-title":"Role of metabolism in drug-induced idiosyncratic hepatotoxicity","volume":"35","author":"Walgren","year":"2005","journal-title":"Crit. Rev. Toxicol."},{"key":"10.1016\/j.toxicon.2025.108366_bib34","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1016\/j.apsb.2022.04.019","article-title":"Landscape of DILI-related adverse drug reaction in China Mainland","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.toxicon.2025.108366_bib35","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.etp.2017.01.003","article-title":"Hepatotoxicity induced by radix Sophorae tonkinensis in mice and increased serum cholinesterase as a potential supplemental biomarker for liver injury","volume":"69","author":"Wang","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"10.1016\/j.toxicon.2025.108366_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2023.110713","article-title":"Matrine disrupts Nrf2\/GPX4 antioxidant system and promotes hepatocyte ferroptosis","volume":"384","author":"Wang","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.toxicon.2025.108366_bib37","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.bbalip.2018.04.005","article-title":"Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis","volume":"1863","author":"Wang","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"10.1016\/j.toxicon.2025.108366_bib38","article-title":"The zebrafish book : a guide for the laboratory use of zebrafish","author":"Westerfield","year":"1995","journal-title":"Danio rerio)"},{"key":"10.1016\/j.toxicon.2025.108366_bib39","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1006\/bbrc.2000.3030","article-title":"Sterol 14-demethylase P450 (CYP51) provides a breakthrough for the discussion on the evolution of cytochrome P450 gene superfamily","volume":"273","author":"Yoshida","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.toxicon.2025.108366_bib40","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/1045345","article-title":"Matrine exerts hepatotoxic effects via the ROS-dependent mitochondrial apoptosis pathway and inhibition of Nrf2-mediated antioxidant response","volume":"2019","author":"You","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"10.1016\/j.toxicon.2025.108366_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.01067","article-title":"A systematic review of the pharmacology, toxicology and pharmacokinetics of matrine","volume":"11","author":"You","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.toxicon.2025.108366_bib42","doi-asserted-by":"crossref","first-page":"T1830","DOI":"10.1111\/1750-3841.12275","article-title":"Identifying 2 prenylflavanones as potential hepatotoxic compounds in the ethanol extract of Sophora flavescens","volume":"78","author":"Yu","year":"2013","journal-title":"J. Food Sci."},{"key":"10.1016\/j.toxicon.2025.108366_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2024.118784","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":"2025","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.toxicon.2025.108366_bib44","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1111\/bph.13209","article-title":"Identification of matrine as a promising novel drug for hepatic steatosis and glucose intolerance with HSP72 as an upstream target","volume":"172","author":"Zeng","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.toxicon.2025.108366_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.aquatox.2021.105938","article-title":"Effects of sublethal concentration of metamifop on hepatic lipid metabolism in adult zebrafish (Danio rerio)","volume":"238","author":"Zhao","year":"2021","journal-title":"Aquat. Toxicol."},{"key":"10.1016\/j.toxicon.2025.108366_bib46","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12920-024-01848-0","article-title":"Comparative analysis of gene expression between mice and humans in acetaminophen-induced liver injury by integrating bioinformatics analysis","volume":"17","author":"Zhao","year":"2024","journal-title":"BMC Med. Genom."},{"key":"10.1016\/j.toxicon.2025.108366_bib47","doi-asserted-by":"crossref","DOI":"10.1016\/j.toxicon.2024.107773","article-title":"Oxymatrine induces apoptosis in non-small cell lung cancer cells by downregulating TRIM46","volume":"244","author":"Zhong","year":"2024","journal-title":"Toxicon"}],"container-title":["Toxicon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010125001400?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010125001400?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T01:50:24Z","timestamp":1762221024000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041010125001400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":47,"alternative-id":["S0041010125001400"],"URL":"https:\/\/doi.org\/10.1016\/j.toxicon.2025.108366","relation":{},"ISSN":["0041-0101"],"issn-type":[{"value":"0041-0101","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The DHCR7 is the key target of lipotoxic liver injury caused by matrine through abnormal activation of the cholesterol synthesis pathway","name":"articletitle","label":"Article Title"},{"value":"Toxicon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxicon.2025.108366","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108366"}}