Metabolomic approach to understand the acute and chronic hepatotoxicity of Veratrum nigrum extract in mice based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry

Abstract

Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically.

Keywords:

• Veratrum nigrum L.
• hepatotoxicity
• metabolomics
• ultra-high-performance liquid chromatography–mass spectrometry

Acknowledgement

The authors express their sincere gratitude to Dagui Chen for his support on animal experiments.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported in part by grants from the National Scientific Foundation of China [grant No. 81302732], Youth Foundation [grant No. 20114Y018] from Shanghai Municipal Commission of Health and Family Planning, TCM Supported Project [grant No. 15401900800] from Science and Technology Commission of Shanghai Municipality.