{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:05:55Z","timestamp":1789031155313,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Sci Food Agric"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Preventing chronic liver damage is essential for maintaining overall health and reducing the risk of serious liver diseases. Acetaminophen (APAP) overdose can lead to severe liver damage due to oxidative stress, and citrus fruits are rich in bioactive compounds that may have health benefits. The present study aimed to examine the hepatoprotective effects of\n                      <jats:italic>Citrus depressa<\/jats:italic>\n                      peel ethanolic extract (CD\u2010EE) and its major compounds, nobiletin (Nob) and tangeretin (Tan), in BALB\/c mice suffering from chronic liver injury caused by APAP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      CD\u2010EE [250 and 500\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      body weight (bw)], Nob (50\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      bw) and Tan (50\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      bw), or\n                      <jats:italic>N<\/jats:italic>\n                      \u2010acetylcysteine (NAC, 600\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      bw, as a positive control), were orally administered to the mice daily for 9\u2009weeks. Subsequently, starting from the second week, mice received intraperitoneal injections of APAP (400\u2009mg\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      bw) twice weekly. We found that APAP\u2010induced liver damage was reduced through the enhancement of antioxidant enzyme activity, the reduction of lipid peroxidation and the modulation of the Nrf2\u2010mediated antioxidant pathway by CD\u2010EE, Nob, Tan and NAC treatments. The levels of DNA methyltransferases and histone deacetylases were influenced by these treatments in epigenetic regulation. Additionally, they partially restored the gut microbiota composition that was altered by APAP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      These results suggest that CD\u2010EE, Nob, and Tan are associated with hepatoprotection against APAP\u2010induced chronic liver injury in mice. The modulation of antioxidant mechanisms and epigenetic regulation potentially contributes to this protection, whereas the restoration of gut microbiota composition may represent an additional pathway. \u00a9 2026 The Author(s).\n                      <jats:italic>Journal of the Science of Food and Agriculture<\/jats:italic>\n                      published by John Wiley &amp; Sons Ltd on behalf of Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsfa.70785","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:19:58Z","timestamp":1781756398000},"page":"7629-7642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>\n                      <i>Citrus depressa<\/i>\n                    <\/scp>\n                    peel extract and its polymethoxyflavones mitigate acetaminophen\u2010induced chronic liver injury in mice through antioxidant activation, epigenetic regulation, and gut microbiota modulation"],"prefix":"10.1002","volume":"106","author":[{"given":"Po\u2010Yao","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Bioscience Technology Chung Yuan Christian University  Taoyuan City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Han","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology Chung Yuan Christian University  Taoyuan City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guor\u2010Jien","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Health Risk Assessment National Yang Ming Chiao Tung University  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang\u2010Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology Chung Yuan Christian University  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