{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:30:35Z","timestamp":1783661435718,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T00:00:00Z","timestamp":1662163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174070"],"award-info":[{"award-number":["82174070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Psoralen and isopsoralen are the pharmacologically important but hepatotoxic components in <jats:italic>Psoraleae Fructus<\/jats:italic>. The purpose of this study was to reveal the underlying mechanism of psoralen\/isopsoralen\u2010induced hepatotoxicity. Initially, we applied integrated analyses of transcriptomic and metabolomic profiles in mice treated with psoralen and isopsoralen, highlighting the xenobiotic metabolism by cytochromes P450 as a potential pathway. Then, with verifications of expression levels by qRT\u2010PCR and western blot, affinities by molecular docking, and metabolic contributions by recombinant human CYP450 and mouse liver microsomes, CYP1A2 was screened out as the key metabolic enzyme. Afterwards, CYP1A2 induction and inhibition models in HepG2 cells and mice were established to verify the role of CYP1A2, demonstrating that induction of CYP1A2 aggravated the hepatotoxicity, and conversely inhibition alleviated the hepatotoxic effects. Additionally, we detected glutathione adducts with reactive intermediates of psoralen and isopsoralen generated by CYP1A2 metabolism in biosystems of recombinant human CYP1A2 and mouse liver microsomes, CYP1A2\u2010overexpressed HepG2 cells, mice livers and the chemical reaction system using UPLC\u2010Q\u2010TOF\u2010MS\/MS. Ultimately, the high\u2010content screening presented the cellular oxidative stress and relevant hepatotoxicity due to glutathione depletion by reactive intermediates. In brief, our findings illustrated that CYP1A2\u2010mediated metabolic activation is responsible for the psoralen\/isopsoralen\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/ptr.7604","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T08:09:25Z","timestamp":1662192565000},"page":"163-180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Transcriptomics and metabolomics reveal the role of <scp>CYP1A2<\/scp> in psoralen\/isopsoralen\u2010induced metabolic activation and hepatotoxicity"],"prefix":"10.1002","volume":"37","author":[{"given":"Cai","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines China 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