{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:27:14Z","timestamp":1786685234759,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background Aflatoxin B1 (AFB1) is a potent hepatotoxic mycotoxin that induces severe oxidative liver damage. Kaempferol (Kae), a natural flavonoid with known antioxidant properties, has unclear protective effects against AFB1-induced hepatotoxicity. This study aimed to evaluate the hepatoprotective role of Kae and elucidate its underlying mechanism using integrated in vivo, in silico, and in vitro approaches. Methods: In vivo (AFB1-challenged mice) and in vitro (hepatocyte) models were employed, combined with network pharmacology, molecular docking, and molecular dynamics simulations. Liver injury indices, oxidative stress markers, antioxidant enzyme activities, and Keap1\/Nrf2 pathway expression were assessed. Results: Kae co-treatment reversed AFB1-induced increases in liver index, serum ALT\/AST, histological lesions, and reduced antioxidant capacity in mice. Network pharmacology revealed 59 common targets, with NFE2L2 (Nrf2) as a key node. In vitro, Kae pretreatment significantly lowered AFB1-elevated ROS, MDA, ALT, and AST, while restoring GSH and total antioxidant capacity. Kae reversed AFB1-induced Keap1 upregulation and Nrf2 downregulation, and increased mRNA levels of HO-1, NQO1, SOD, GPX1, and CAT. Molecular docking and simulation showed stable Kae\u2013Keap1 binding (\u22129.6 kcal\/mol) with critical hydrogen bonds (VAL-606) and van der Waals contacts. Conclusions: Kae directly binds Keap1, activates Nrf2 signaling, upregulates antioxidant gene expression, and mitigates AFB1-induced oxidative liver injury. These findings support Kae as a promising candidate for preventing AFB1 hepatotoxicity.<\/jats:p>","DOI":"10.3390\/nu18162633","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:53:48Z","timestamp":1786539228000},"page":"2633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kaempferol Alleviates Aflatoxin B1-Induced Liver Injury by Mitigating Oxidative Stress"],"prefix":"10.3390","volume":"18","author":[{"given":"Zongmin","family":"Shu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Bi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-0767","authenticated-orcid":false,"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Teaching Demonstration Center of the Basic Experiments of Agricultural Majors, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez, J., Hern\u00e1ndez-Rodr\u00edguez, M., M\u00e9ndez-Albores, A., T\u00e9llez-Isa\u00edas, G., Mera Jim\u00e9nez, E., Nicol\u00e1s-V\u00e1zquez, M.I., and Miranda Ruvalcaba, R. 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