{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:43Z","timestamp":1786566523732,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Excessive copper (Cu) accumulation induces hepatotoxicity, while the natural flavonoid kaempferol (KA) exhibits potent antioxidant and anti\u2010inflammatory activities. This study explored the protective effects of kaempferol against copper overload\u2010induced liver injury in rats and the underlying molecular mechanisms. A copper overload model was established in Sprague\u2010Dawley (SD) rats through the administration of copper sulfate (CuSO\u2084) over 12 weeks, followed by kaempferol intervention. Comprehensive evaluations were conducted on hepatic copper accumulation, liver function indices, histopathological alterations, and associated molecular pathways. Western blot analysis demonstrated that kaempferol mitigated copper\u2010induced liver damage by upregulating Sirt1, which subsequently activated the Nrf2\/FOXO3 signaling pathway, thereby reducing oxidative stress, inflammation, and hepatocyte apoptosis. Metabolomics analysis further revealed that kaempferol influenced metabolic pathways, including lysine degradation and cysteine\u2010methionine metabolism, indicating its multi\u2010target and multi\u2010pathway regulatory effects. In conclusion, kaempferol mitigates copper\u2010induced liver injury through complex molecular networks, providing novel insights into therapeutic approaches for liver diseases associated with copper metabolism and underscoring the multi\u2010mechanistic potential of natural compounds.<\/jats:p>","DOI":"10.1002\/jbt.70813","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:48:32Z","timestamp":1774612112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kaempferol Mitigates Liver Injury Induced by Copper Toxicity Through the Activation of the Sirt1\/Nrf2\/FOXO3 Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8449-4029","authenticated-orcid":false,"given":"Jiaying","family":"Xu","sequence":"first","affiliation":[{"name":"College of Life Sciences China Jiliang University Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangjun","family":"Wan","sequence":"additional","affiliation":[{"name":"Technology Center of Hangzhou Customs Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haishuo","family":"Mu","sequence":"additional","affiliation":[{"name":"College of Life Sciences China Jiliang University Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxiang","family":"Gong","sequence":"additional","affiliation":[{"name":"College of Life Sciences China Jiliang University Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Sericulture and Tea Zhejiang Academy of Agricultural Sciences Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-795X","authenticated-orcid":false,"given":"Tongle","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Life Sciences China Jiliang University Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2023.115738"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10661-021-08997-0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43188-020-00043-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012267.pub2"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.04.033"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-019-05345-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914459"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2022.113369"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2016.03.010"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2015.05.002"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1596481"},{"key":"e_1_2_10_13_1","first-page":"627","article-title":"Recent Studies on Kaempferol and Its Biological and Pharmacological Activities","volume":"19","author":"Kim J. 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