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Given the lack of effective pharmacological treatments, flavonoid-rich fruits have attracted growing attention as potential intervention strategies. This study investigated the independent and combined effects of extracts from Citri reticulatae pericarpium (CRPE) and Chaenomeles speciosa (Sweet) Nakai (CSPE), previously shown to possess hepatoprotective properties, in a mouse model of ethanol-induced chronic ALI. The flavonoid composition of CRPE and CSPE was characterized using LC-MS\/MS, and their potential mechanisms of action were further elucidated through transcriptomic analysis. The results showed that CRPE and CSPE, whether administered individually or in combination, effectively alleviated alcohol-induced hepatic histological damage and inflammatory responses. Furthermore, both extracts significantly reduced OS and improved lipid metabolism. Notably, CRPE, CSPE, and their combination regulated the gut microbiota, as shown by increased abundances of beneficial bacteria such as Lactobacillus and Bifidobacterium, along with elevated levels of short-chain fatty acids (SCFAs). These findings highlight that combinations of multiple fruit extracts exhibit significant potential in alleviating ALI by modulating the gut microbiota, providing valuable insights for the development of functional foods.<\/jats:p>","DOI":"10.3390\/antiox14030343","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:07:51Z","timestamp":1741957671000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatoprotective Effects of Citri reticulatae Pericarpium and Chaenomelese speciosa (Sweet) Nakai Extracts in Alcohol-Related Liver Injury: Modulation of Oxidative Stress, Lipid Metabolism, and Gut Microbiota"],"prefix":"10.3390","volume":"14","author":[{"given":"Shuangshuang","family":"Ma","sequence":"first","affiliation":[{"name":"Longping Branch, College of Biology, Hunan University, Changsha 410125, China"},{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingtao","family":"Kang","sequence":"additional","affiliation":[{"name":"Longping Branch, College of Biology, Hunan University, Changsha 410125, China"},{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Fisheries, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoping","family":"Pan","sequence":"additional","affiliation":[{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lvhong","family":"Huang","sequence":"additional","affiliation":[{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Liao","sequence":"additional","affiliation":[{"name":"Longping Branch, College of Biology, Hunan University, Changsha 410125, China"},{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajing","family":"Guo","sequence":"additional","affiliation":[{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhua","family":"Fu","sequence":"additional","affiliation":[{"name":"Longping Branch, College of Biology, Hunan University, Changsha 410125, China"},{"name":"Dongting Laboratory, Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/lt.25600","article-title":"Introducing the 2019 American Association for the Study of Liver Diseases Guidance on Alcohol-Associated Liver Disease","volume":"26","author":"Lucey","year":"2020","journal-title":"Liver Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.14309\/ajg.0000000000002572","article-title":"ACG Clinical Guideline: Alcohol-Associated Liver Disease","volume":"119","author":"Jophlin","year":"2024","journal-title":"Am. 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