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Fermentation is reported to enhance the level and biological activities of various bio-constituents of plant extracts. Therefore, this study was undertaken to evaluate the effects of fermented <jats:italic>H. dulcis<\/jats:italic> extract (FHDE) on ethanol-induced liver injury in mice.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>FHDE was prepared using <jats:italic>Bacillus subtilis<\/jats:italic> and <jats:italic>Lactobacillus plantarum.<\/jats:italic> The effects of FHDE on ethanol-induced liver injury were evaluated in C57BL\/6\u2009N CrSlc mice. A mixed feed preparation containing the fermented extract with and without ethanol was given to mice for 29\u2009days, according to its group. At the end of the experiment, blood and liver samples were collected from all mice in the group. Plasma biochemical analysis and histopathological investigation were performed to evaluate the impacts of treatment on the biomarkers of hepatic damage and inflammatory changes. Besides, the expression of genes that regulate the activities of enzymes associated with alcohol metabolism, antioxidant activity, and fatty acid oxidation was assessed using a quantitative real-time polymerase chain reaction. Moreover, the amino acid contents and the active ingredients of the extract were evaluated before and after fermentation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Fermentation resulted in a marked increase and decrease in the amount of Gamma-Amino-n-butyric acid (GABA) and glutamic acid, respectively. FHDE enhanced the body weight gain of mice compared to ethanol. Besides, plasma levels of triglyceride, low-density lipoprotein, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly (<jats:italic>P\u2009&lt;\u20090.05<\/jats:italic>) reduced in the FHDE-treated groups relative to the ethanol-treated control. FHDE upregulated the expression of genes associated with enzymes involved in alcohol dehydrogenation (<jats:italic>Adh1<\/jats:italic> and <jats:italic>Aldh2<\/jats:italic>), antioxidant activity (<jats:italic>SOD<\/jats:italic> and <jats:italic>CAT<\/jats:italic>), and fatty acid oxidation (<jats:italic>PPAR-\u03b1<\/jats:italic> and <jats:italic>PGC-1\u03b1<\/jats:italic>). However, the expressions of Cytochrome peroxidase <jats:italic>Cyp<\/jats:italic><jats:sub><jats:italic>2<\/jats:italic><\/jats:sub><jats:italic>E<\/jats:italic><jats:sub><jats:italic>1<\/jats:italic><\/jats:sub> and genes related to lipogenesis (<jats:italic>SREBP-1c<\/jats:italic>, <jats:italic>FAS<\/jats:italic>, <jats:italic>SCD-1<\/jats:italic>, and <jats:italic>ACC<\/jats:italic>) were significantly (<jats:italic>P\u2009&lt;\u20090.05<\/jats:italic>) downregulated following treatment with the FHDE. Histopathological investigation demonstrated a slight degree of inflammatory cell infiltration and occasional fatty changes in the FHDE-treated groups.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The GABA-enriched fermented <jats:italic>H. dulcis<\/jats:italic> extract prevented ethanol-induced hepatic damage by enhancing the antioxidant defense system, fatty acid oxidation, and reducing lipogenesis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12906-020-2866-0","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T17:02:31Z","timestamp":1583514151000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hepatoprotective effects of gamma-aminobutyric acid-enriched fermented Hovenia dulcis extract on ethanol-induced liver injury in mice"],"prefix":"10.1186","volume":"20","author":[{"given":"Na-Hye","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham Fikru","family":"Mechesso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naila","family":"Boby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quah","family":"Yixian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woong-Kyu","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam-Pin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Suk","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-1499","authenticated-orcid":false,"given":"Seung-Chun","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,6]]},"reference":[{"key":"2866_CR1","doi-asserted-by":"publisher","first-page":"14787","DOI":"10.3748\/wjg.v20.i40.14787","volume":"20","author":"E Madrigal-Santill\u00e1n","year":"2014","unstructured":"Madrigal-Santill\u00e1n E, Madrigal-Bujaidar E, \u00c1lvarez-Gonz\u00e1lez I, Sumaya-Mart\u00ednez MT, Guti\u00e9rrez-Salinas J, Bautista M, et al. 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