{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:06:13Z","timestamp":1788296773413,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013128","name":"Korea Technology and Information Promotion Agency for SMEs","doi-asserted-by":"publisher","award":["S2983880"],"award-info":[{"award-number":["S2983880"]}],"id":[{"id":"10.13039\/501100013128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 \u03bcM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB\/c mice induced by CCl4 through the intraperitoneal injection of 1 mL\/kg CCl4 and co-administration of 5-DN at (1 and 2 mg\/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)\/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.<\/jats:p>","DOI":"10.3390\/ijms22031083","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T11:13:53Z","timestamp":1611314033000},"page":"1083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-8041","authenticated-orcid":false,"given":"Sukkum Ngullie","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea"},{"name":"Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea"},{"name":"School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasish Kumar","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Min","family":"Park","sequence":"additional","affiliation":[{"name":"Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omaima","family":"Nasif","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University (Medical City), King Khalid University Hospital, P.O. Box 2925, Riyadh 11461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek K.","family":"Bajpai","sequence":"additional","affiliation":[{"name":"Department of Energy and Materials Engineering, Dongguk University-Seoul, 30 Pildong-ro 1-gil, Seoul 04620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Chul","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Daegu University, Gyeongsan 38453, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintae","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6757-0241","authenticated-orcid":false,"given":"Jae Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"Advanced Bio Convergence Center (ABCC), Pohang Technopark Foundation, Pohang 37668, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.biocel.2013.02.019","article-title":"The UDP-glucuronosyltransferases: Their role in drug metabolism and detoxification","volume":"45","author":"Rowland","year":"2013","journal-title":"Int. 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