Abstract

Monascus-fermented red mold rice (RMR) has excellent physiological efficacy on lipid metabolism and liver function. This study investigated the ameliorative effects of monascin (MS) from RMR on alcoholic liver injury (ALI) in mice, and further illustrated its mechanism of action. Results indicated that dietary MS intervention obviously ameliorated lipid metabolism and liver function in mice with over-drinking. In addition, MS intervention alleviated alcohol-induced oxidative stress in the liver by reducing the hepatic activities of lactate dehydrogenase (LDH) and hepatic levels of malondialdehyde (MDA), increasing the hepatic activities of catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH) and hepatic levels of glutathione (GSH). 16S rRNA amplicon sequencing showed that excessive drinking had a significant effect on the composition of the gut microbiota in mice. MS intervention was beneficial to ameliorate intestinal microbiota dysbiosis by elevating the proportion of Lactobacillus, Lachnospiraceae_UCG-006, Coriobacteriales, etc., but decreasing the proportion of Staphylococcus, Muribaculaceae, Desulfovibrionaceae, etc. Additionally, correlation analysis indicated that the key intestinal bacterial taxa intervened by MS were closely related to some biochemical indicators of lipid metabolism, liver function and oxidative stress. Moreover, liver metabolomics analysis revealed that dietary MS supplementation significantly regulated the levels of liver metabolites involved in taurine and hypotaurine metabolism, riboflavin metabolism, and purine metabolism, etc. Furthermore, MS intervention regulated gene transcription and protein expression associated with lipid metabolism and oxidative stress in the liver. In short, these findings suggest that MS mitigates alcohol-induced hepatic oxidative damage through modulating the intestinal microbiome and liver metabolic pathway, and thus can be served as a functional component to prevent alcoholic liver disease.

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