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In this study, a wild G. tsugae strain (G42) with high triterpenoid content was screened from nine strains by rice solid-state fermentation, and 53.86 mg\/g triterpenoids could be produced under optimized conditions; that is, inoculation amount 20%, fermentation temperature 27 \u00b0C, and culture time 45 days. The hepatoprotective activity of G42 ethanol extract was evaluated by CCl4-induced liver injury in mice, in which changes in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidation-related factors, and inflammatory cytokines in serum or liver samples demonstrated the therapeutic effect. In addition, the ethanol extract of G42 reduced the incidence of necrosis and inflammatory infiltration, and decreased protein expression levels of phosphor-nuclear factor-\u03baB (NF-\u03baB), interleukin-I\u03b2 (IL-1\u03b2), and nuclear factor erythroid-2-related factor 2 (NRF2). The chemical composition of the ethanol extract was analyzed by high-resolution mass spectrometry and molecular networking. Three main triterpenoids, namely platycodigenin, cucurbitacin IIb, and ganolecidic acid B were identified. This work provided an optimized fermentation method for G. tsugae, and demonstrated that its fermentation extract might be developed as a functional food with a hepatoprotective effect.<\/jats:p>","DOI":"10.3390\/molecules27165347","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T21:30:34Z","timestamp":1661203834000},"page":"5347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hepatoprotective Activity of Ethanol Extract of Rice Solid-State Fermentation of Ganoderma tsugae against CCl4-Induced Acute Liver Injury in Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Xin","family":"Zhang","sequence":"first","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Lv","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongping","family":"Fu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Mudanjiang Branch of Heilongjiang Academy of Agricultural Sciences, Mudanjiang 157000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Chen","sequence":"additional","affiliation":[{"name":"ShouXianGu Botanical Drug Institute, Hangzhou 311100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerong","family":"Han","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Li","sequence":"additional","affiliation":[{"name":"ShouXianGu Botanical Drug Institute, Hangzhou 311100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1055\/s-2007-1007249","article-title":"Mechanisms of liver damage","volume":"16","author":"Losser","year":"1996","journal-title":"Semin. 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