Research Article Details
| Article ID: | A46964 |
| PMID: | 32129352 |
| Source: | Food Funct |
| Title: | Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis. |
| Abstract: | 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. |
| DOI: | 10.1039/c9fo02357g |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D201 | L-Carnitine | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |
| D522 | Caffeic acid | Chemical drug | -- | STAT3 transcription factor inhibitor | -- | Under clinical trials | Details |
| D062 | Carnitine complex | Supplement | DB00583 | SLC22A4; SLC22A5; CRAT; MPO | -- | Under clinical trials | Details |