PUBLICATION

Integrated approach toward absorption, distribution, metabolism, and excretion of Xiaoke pills in zebrafish based on UPLC-HRMS and DESI-MS techniques

Authors
Zhu, C., Jiang, X., Tian, J., Chen, J., Lin, C., Wang, C., Tie, C., Li, M., Wu, C.
ID
ZDB-PUB-220511-11
Date
2022
Source
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences   1200: 123276 (Journal)
Registered Authors
Li, Mingyu
Keywords
ADME, DESI-MS, UPLC-HRMS, Xiaoke pills, Zebrafish
MeSH Terms
  • Animals
  • Chromatography, High Pressure Liquid/methods
  • Chromatography, Liquid
  • Drugs, Chinese Herbal*/chemistry
  • Mass Spectrometry
  • Medicine, Chinese Traditional/methods
  • Rats
  • Spectrometry, Mass, Electrospray Ionization/methods
  • Zebrafish*/metabolism
PubMed
35537310 Full text @ J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
Abstract
Traditional Chinese medicine (TCM) has been used in clinical settings for over 2000 years in China. The study of the absorption, distribution, metabolism, and excretion (ADME) of TCM in vivo could be beneficial for the discovery of the active components in TCM. However, the conventional strategies used for ADME research are based on rodent models and have the characteristics of lengthy experimental periods, complex processes, and extensive data processing, which make it difficult to perform rapid analyses and high-throughput ADME screening of the medicinal components of TCM. In this study, an integrated high-throughput research strategy for the in vivo ADME analysis of TCM was established based on a zebrafish model. Accordingly, a combination of ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS), desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, and in-house non-targeted precise-and-thorough background-subtraction (PATBS) data post-processing techniques were successfully applied for the analysis of the metabolism of zebrafish exposed to Xiaoke pills. A total of 49 compounds related to Xiaoke pills (including 13 prototypical components and 36 metabolites) were detected in zebrafish. In total, 32 of them, including puerarin, daidzein, deoxyschizandrin, formononetin, and glibenclamide, which have been identified to have hypoglycemic activity in our previous studies and are phase I and phase II metabolites resulting from the hydroxylation, demethylation, glucuronidation, sulfation, and glycosylation of the prototypical components in vivo, were found in rats treated with Xiaoke pills. Furthermore, the overall distribution of the known compounds in zebrafish exposed to Xiaoke pills was explored using DESI-MS. In summary, this study provides a practical approach for the high-throughput screening of the active components of TCM using a zebrafish model.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping