Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis
Recent studies have demonstrated that rosmarinic acid is a valuable natural product for treatment of alcoholic liver disease. However, the mechanisms whereby rosmarinic acid improves alcoholic liver disease remain unclear. Here we demonstrated that rosmarinic acid reduced ethanol-induced lipid accumulation in mouse AML12 cells by oil-red O staining. It was shown that rosmarinic acid prevented ethanol-induced elevation of malondialdehyde level. We also found that rosmarinic acid inhibited ethanol-induced mRNA expression of tumor necrosis factor-α and interleukin 6. Metabolomics analysis revealed that rosmarinic acid ameliorated ethanol-induced fatty acid biosynthesis in the cytoplasm. In addition, palmitic acid was a candidate biomarker in cells exposed to ethanol or ethanol plus rosmarinic acid. D-Glucose, sorbitol and D-fructose that are components of polyol pathway decreased in ethanol-intoxicated cells treated with rosmarinic acid. Moreover, we confirmed that rosmarinic acid attenuated ethanol-induced mRNA expression of fatty acid synthase, probably by modulating AMPK/SREBP-1c pathway. Furthermore, rosmarinic acid prevented ethanol-induced decreases in eight metabolites that are involved in mitochondrial metabolism, including glycine and succinic acid which are components of carnitine synthesis. These results provide a crucial insight into the molecular mechanism of rosmarinic acid in alleviating ethanol-induced injury.