Metabolomic mechanisms of gypenoside against liver fibrosis in rats: An integrative analysis of proteomics and metabolomics data

AIMS: To investigate mechanisms and altered pathways of gypenoside against carbon tetrachloride (CCl(4))-induced liver fibrosis based on integrative analysis of proteomics and metabolomics data. METHODS: CCl(4)-induced liver fibrosis rats were administrated gypenoside. The anti-fibrosis effects were evaluated by histomorphology and liver hydroxyproline (Hyp) content. Protein profiling and metabolite profiling of rats liver tissues were examined by isobaric tags for relative and absolute quantitation (iTRAQ) approach and gas chromatography-mass spectrometer (GC-MS) technology. Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data. The levels of some key proteins in altered pathways were determined by western blot. RESULTS: Histopathological changes and Hyp content in gypenoside group had significant improvements (P<0.05). Compared to liver fibrosis model group, we found 301 up-regulated and 296 down-regulated proteins, and 9 up-regulated and 8 down-regulated metabolites in gypenoside group. According to integrative analysis, some important pathways were found, including glycolysis or gluconeogenesis, fructose and mannose metabolism, glycine, serine and threonine metabolism, lysine degradation, arginine and proline metabolism, glutathione metabolism, and sulfur metabolism. Furthermore, the levels of ALDH1B1, ALDH2 and ALDH7A1 were found increased and restored to normal levels after gypenoside treated (P<0.05). CONCLUSIONS: Gypenoside inhibited CCl(4)-induced liver fibrosis, which may be involved in the alteration of glycolysis metabolism and the protection against the damage of aldehydes and lipid peroxidation by up-regulating ALDH.