{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:25:07Z","timestamp":1777868707438,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acetaminophen (APAP)\u2010induced liver injury (AILI) remains a critical clinical challenge with limited therapeutic options. This research elucidates the mechanisms through which the natural flavonoid isobavachin (ISO) confers protection against APAP\u2010induced liver injury. In vivo experiments demonstrated that ISO treatment significantly attenuated histopathological parameters, oxidative stress and inflammation, as indicated by serum ALT\/AST, MDA, SOD\/GSH, TNF\u2010\u03b1\/IL\u20101\u03b2 levels. Mechanistically, ISO inhibited CYP2E1 expression and promoted NRF2 activation. Furthermore, integrated network pharmacology, transcriptomics, and molecular docking simulations revealed the PI3K\/AKT signaling pathway as a potential targets of ISO, demonstrating high\u2010affinity confirmed between ISO and PI3K (\u20108.6\u2009kcal\/mol) or AKT (\u20106.4\u2009kcal\/mol) respectively. western blotting assay confirmed that ISO activated PI3K\/AKT signaling and upregulated downstream anti\u2010apoptotic\u2010 protein BCL2. These findings collectively suggest that ISO alleviates AILI through multi\u2010mechanisms: inhibiting CYP2E1\u2010mediated APAP bioactivation, modulating of the NRF2\/PI3K\/AKT signaling, ISO attenuates oxidative damage, suppresses inflammatory activation, and inhibits apoptosis. The results suggest that ISO represents a potential therapeutic agent for managing APAP\u2010induced hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jbt.70682","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T04:53:09Z","timestamp":1767934389000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isobavachin Ameliorates Acetaminophen\u2010Induced Liver Injury Through Modulation of CYP2E1\u2010Mediated Bioactivation and NRF2\/PI3K\/AKT Cytoprotective Pathways"],"prefix":"10.1002","volume":"40","author":[{"given":"Wenjie","family":"Ye","sequence":"first","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-4840","authenticated-orcid":false,"given":"Shuaishuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain, Cognition and Education Sciences, Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education South China Normal University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youxi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain, Cognition and Education Sciences, Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education South China Normal University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zitao","family":"Guo","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexin","family":"Xu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenkun","family":"Wu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhong","family":"Huang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0053-2723","authenticated-orcid":false,"given":"Jianxin","family":"Pang","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; Guangdong Provincial Key Laboratory of New Drug Screening &amp; Guangdong\u2010Hongkong\u2010Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-051122-094016"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.04.019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.11.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27248855"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6503"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156050"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.05.012"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2022.2139431"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116753"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.03.026"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.08.038"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.081082098"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108023"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO02736G"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154766"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.11.009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfac094"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04840-x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17070893"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.106298"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1302"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17787"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2023.106637"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-024-00631-4"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117280"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.06.038"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2179781"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202400172"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111939"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.11.004"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.01.079"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2024.106829"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2022.06.002"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112781"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155382"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110375"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.04.023"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21004"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.143"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2018.06.001"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70682","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70682","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:29:21Z","timestamp":1777552161000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jbt.70682"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70682","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70682"}}