{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T19:03:04Z","timestamp":1779822184336,"version":"3.53.1"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Heatstroke\u2010induced acute liver injury (HS\u2010ALI) is primarily driven by hepatic oxidative stress and inflammation.\n                    <jats:italic>Acacetin<\/jats:italic>\n                    (5,7\u2010dihydroxy\u20104\u2032\u2010methoxyflavone, AC) is a naturally occurring O\u2010methylated flavone derived from\n                    <jats:italic>Chrysanthemum<\/jats:italic>\n                    \u00d7\n                    <jats:italic>morifolium<\/jats:italic>\n                    (Ramat.) Hemsl., a hybrid species with the parentage\n                    <jats:italic>C. argyrophyllum<\/jats:italic>\n                    \u00d7\n                    <jats:italic>C. dichrum<\/jats:italic>\n                    \u00d7\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. indicum<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u00d7\n                    <jats:italic>C. nankingense<\/jats:italic>\n                    \u00d7\n                    <jats:italic>C. zawadzkii<\/jats:italic>\n                    . Known for its antioxidant, hepatoprotective, and anti\u2010inflammatory properties, this compound has not been previously investigated for its effects on HS\u2010ALI. This study integrated network pharmacology, molecular docking, molecular dynamics simulations (MDS), and in\u00a0vivo experiments to evaluate the efficacy and mechanism of AC. Mice were randomized into normal control, heatstroke control, AC\u2010pretreated (25 or 50\u2009mg\/kg\/d) heatstroke groups, as well as groups treated with the c\u2010Jun (protein symbol JUN; encoded by the\n                    <jats:italic>Jun<\/jats:italic>\n                    gene) and its N\u2010terminal kinase activator (\n                    <jats:italic>anisomycin<\/jats:italic>\n                    ) alone or in combination with AC (50\u2009mg\/kg\/d). Liver injury, oxidative stress, the c\u2010Jun and prostaglandin\u2010endoperoxide synthase 2 (PTGS2) pathway, and ferroptosis were assessed using histopathology, western blot, and quantitative polymerase chain reaction (qPCR). Network pharmacology and molecular docking identified JUN and PTGS2 as core targets of AC, demonstrating stable binding, which was further validated by MDS. In\u00a0vivo, AC pretreatment significantly alleviated histopathological damage and oxidative stress, suppressed activation of the c\u2010Jun\/PTGS2 pathway, and inhibited key markers of hepatic ferroptosis\u2014effects that were confirmed in agonist challenge experiments. In conclusion, AC ameliorates HS\u2010ALI likely by inhibiting the c\u2010Jun\/PTGS2 axis and attenuating ferroptosis, highlighting its potential as a candidate compound for HS\u2010ALI.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70308","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:24:58Z","timestamp":1777703098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acacetin Attenuates Heatstroke\u2010Induced Acute Liver Injury by Targeting the c\u2010Jun\/\n                    <scp>PTGS2<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"107","author":[{"given":"Xiaolong","family":"Shu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Xinjiang Medical University  Urumqi Xinjiang 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