{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T02:19:56Z","timestamp":1773454796662,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81891011"],"award-info":[{"award-number":["81891011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Acetaminophen (paracetamol) overdose has emerged as a major cause of drug\u2010induced liver failure, and effective clinical treatment is limited. This study investigated the effects of ginsenoside Rf, a natural product from the Chinese herbal medicine ginseng, on acetaminophen\u2010induced liver injury (AILI) in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The protective effects of ginsenoside Rf against AILI were evaluated using cellular and mouse models. RNA sequencing and subsequent experimental validations were conducted to investigate the mechanisms of ginsenoside Rf against AILI. A pull\u2010down assay was used to identify the potential targets of ginsenoside Rf.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Pretreatment with ginsenoside Rf significantly alleviated AILI. Ginsenoside Rf also inhibited acetaminophen\u2010induced excessive oxidative stress, inflammatory response, hepatocellular apoptosis and abnormalities in bile acid metabolism. One protein, cell cycle and apoptosis regulator 2 (CCAR2), was identified as a specific target of ginsenoside Rf. By binding with CCAR2, ginsenoside Rf significantly disrupted acetaminophen overdose\u2010induced interaction of CCAR2 with the deacetylase sirtuin 1 (SIRT1), thereby reducing farnesoid X receptor (FXR) acetylation modification. Simultaneously, ginsenoside Rf up\u2010regulated FXR, facilitating its nuclear translocation, and transcriptionally activating its target genes required for bile acid metabolism. Liver\u2010specific\n                      <jats:italic>Ccar2<\/jats:italic>\n                      gene deletion attenuated acetaminophen\u2010induced mice liver injury and abolished the hepatoprotective effects of ginsenoside Rf in AILI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Collectively, these findings propose CCAR2 as a potential target to prevent AILI. Ginsenoside Rf exhibits a significant hepatoprotective effect against AILI through the CCAR2\u2010SIRT1\u2010FXR signalling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70406","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:34:06Z","timestamp":1773452046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Rf protects against acetaminophen\u2010induced liver injury by targeting CCAR2 to activate the SIRT1\u2010FXR signalling pathway"],"prefix":"10.1111","author":[{"given":"Jingjing","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and 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