Metabolomics and Microbiomics Perspectives Reveal the Regulatory Pathways of Monaphilone B Derived From Red Yeast Rice on Alcoholic Liver Injury in Mice

Abstract

Red yeast rice (RYR) has been extensively used as a natural food for thousands of years and still plays an important role in the world food industry. In this study, the protective effect and the mechanism of monaphilone B (MB) from RYR on alcoholic liver injury were investigated in mice. The results showed that MB effectively ameliorated alcohol-induced liver lipid metabolism (decreasing serum total cholesterol [TC], triglyceride [TG], low-density lipoprotein cholesterol [LDL-C], and increasing high-density lipoprotein cholesterol [HDL-C]), oxidative stress (decreasing hepatic maleic dialdehyde [MDA] level, increasing catalase [CAT], superoxide dismutase [SOD], alcohol dehydrogenase [ADH] and glutathione [GSH] hepatic activities), and inflammatory response (decreasing hepatic lipopolysaccharide [LPS], tumor necrosis factor-α [TNF-α], Interferon-γ [IFN-γ] and interleukin 6 [IL-6]), repaired liver function (reducing serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and liver lactate dehydrogenase [LDH] activity). 16S amplicon sequencing showed that MB administration effectively modulated intestinal flora and its metabolism, which were highly correlated with the improvement of liver function and intestinal barrier function. Liver metabolomics analysis indicated that MB administration regulated 69 liver potential biomarkers involved in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, tryptophan metabolism, and so on. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) analysis revealed that MB administration modulated gene transcription and protein expression related to liver lipid metabolism and oxidative stress. These findings provide scientific evidence that MB has the biological activity to ameliorate alcohol-induced lipid metabolism disorders, liver oxidative stress, and enterobacterial dysbiosis.