Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis

• Published in: Food & function 2020-03, Vol.11 (3), p.294-216
• Main Authors: Guo, Chang, Shangguan, Yu, Zhang, Meiru, Ruan, Yanxin, Xue, Guoqing, Ma, Jingfan, Yang, Jian, Qiu, Longxin
• Format: Article
• Language: English
• Subjects: Accumulation; Animals; Biomarkers; Biosynthesis; Carnitine; Cell Line; Cinnamates - pharmacology; Cytoplasm; Depsides - pharmacology; Ethanol; Ethanol - pharmacology; Fatty acids; Fatty Acids - biosynthesis; Fatty-acid synthase; Gene expression; Glycine; Hepatocytes - drug effects; Hepatocytes - metabolism; Interleukin 6; Lipid Metabolism; Lipids; Liver; Liver diseases; Malondialdehyde; Medical treatment; Metabolism; Metabolites; Metabolomics; Mice; Mitochondria; Natural products; Palmitic acid; Rosmarinic Acid; Sorbitol; Sterol regulatory element-binding protein; Stress, Physiological; Succinic acid; Tumor necrosis factor-α
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo02357g

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 performed experiments using a non-transformed mouse hepatocyte cell line (AML12). Oil-red O staining demonstrated that rosmarinic acid reduced ethanol-induced lipid accumulation. It was shown that rosmarinic acid prevented ethanol-induced elevation of the 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. Rosmarinic acid prevented the ethanol-induced increase in sorbitol that is a component of the polyol pathway. Moreover, we confirmed that rosmarinic acid attenuated ethanol-induced mRNA expression of fatty acid synthase, probably by modulating the AMPK/SREBP-1c pathway. Furthermore, rosmarinic acid prevented the ethanol-induced decrease in eight metabolites that are involved in mitochondrial metabolism, including glycine and succinic acid which are the components of carnitine synthesis. These results provide a crucial insight into the molecular mechanism of rosmarinic acid in alleviating ethanol-induced injury. Rosmarinic acid ameliorates ethanol-induced lipid accumulation by reducing fatty acid biosynthesis and tumor necrosis factor-α.