Serum metabonomics characterization of liver fibrosis induced by bile duct-ligated in rats and the intervention effects of herb compound 861

Abstract

Liver fibrosis has been increasingly recognized as a cause for high morbidity and mortality of some diseases in humans. Herbal medicines have received great attention due to their low side effects and high safety. Herbal compound 861 (Cpd 861) has been effectively used for treating hepatic fibrosis for long time. Yet, its exact mechanism is still in fancy. Herein, we first established a liver fibrosis model by bile duct ligation (BDL), which led to the toxic accumulation of bile acids in animals, resulting in hepatic fibrosis. A serum metabonomics study on BDL-induced liver fibrosis rats after Cpd 861 treatment was performed using UHPLC-QTOF/MS. Multivariate analysis showed that Cpd 861 significantly reversed the metabolic perturbation induced by BDL to normal state, which is in agreement with the serum biochemical and histopathological findings. 15 metabolites were screened as potential biomarkers. Eight metabolic pathways were recognized as the most relevant pathways, involving dysfunction of amino acids metabolism and synthesis, fatty acid metabolism, phospholipids metabolism, and others. This is the first study to reveal the underlying mechanism of Cpd 861 based on metabonomics, which is complementary to biochemical analysis, and more importantly, a potentially powerful tool to interpret the mechanisms of extremely complex systems.

GRAPHICAL ABSTRACT

Keywords:

• Bile duct ligation
• hepatic fibrosis
• herbal compounds
• LC-MS
• metabolic pathways
• serum metabonomics

Acknowledgements

This study was supported by the National Natural Science Foundation of China [No. 81341090].

Conflict of interest

All of the authors claim that there is no conflict of interests among the authors.

Author contributions statement

XL, CZ performed the investigation, analyzed the data and wrote the paper; XQ, JJ and ZM designed the study and amended the paper; XY and RL helped in execution of research. All the other authors read, improved and approved themanuscript.