Liver metabolomic characterization of Sophora flavescens alcohol extract-induced hepatotoxicity in rats through UPLC/LTQ-Orbitrap mass spectrometry

Abstract

1. This study aimed to observe the influence of Sophora flavescens alcohol extract (SFAE) on hepatic metabolic profiling in rats to explore the possible mechanism of hepatotoxicity induced by S. flavescens.

2. Male Sprague–Dawley rats were randomly divided into three groups (n = 6 in each group) and administered with SFAE at different doses of 0, 1.25 and 2.5 g/kg for two weeks. Ultra-performance liquid chromatography–high resolution mass spectrometry was utilized to detect the change in the metabolites in rat liver. Principal component analysis and orthogonal partial least squares discriminant analysis were adapted to perform multivariate statistical analysis between groups and to screen the potential biomarkers. Related metabolic pathway analysis was also conducted.

3. Results indicated that hepatic metabolites in the three groups were separated on day 14, and 25 major differential metabolites were identified. Six bile acids, four carnitines, four lysophosphatidylcholines and glutathione were closely related to hepatotoxicity. Liver metabolomic results showed that rats orally exposed to SFAE exhibited a disturbance of the metabolism of bile acids, fatty acids, glycerophospholipids and amino acids.

4. This study provided new insights into the possible mechanism of hepatotoxicity induced by SFAE in rats.

Keywords:

• Hepatotoxicity
• high-resolution mass spectrometry
• metabolomics
• Sophora flavescens
• liver tissue

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the Fundamental Research Funds for the Central Universities [WK9110000017] and the National Natural Science Foundation of China [No. 81803832].