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

Chronic and excessive alcohol consumption induces alcohol-related liver injury (ALI), characterized by oxidative stress (OS), disrupted lipid metabolism, and gut microbiota dysbiosis. 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 <i>Citri reticulatae</i> pericarpium (CRPE) and <i>Chaenomeles speciosa</i> (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 <i>Lactobacillus</i> and <i>Bifidobacterium</i>, 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.