PUBLICATION

Combined in vivo imaging and omics approaches reveal metabolism of icaritin and its glycosides in zebrafish larvae

Authors
Li, Z.H., Alex, D., Siu, S.O., Chu, I.K., Renn, J., Winkler, C., Lou, S., Tsui, S.K., Zhao, H.Y., Yan, W.R., Mahady, G.B., Li, G.H., Kwan, Y.W., Wang, Y.T., and Lee, S.M.
ID
ZDB-PUB-110429-16
Date
2011
Source
Molecular Biosystems   7(7): 2128-38 (Journal)
Registered Authors
Li, Zhen, Renn, Joerg, Wang, Yi, Winkler, Christoph
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Bone and Bones/drug effects
  • Bone and Bones/metabolism
  • Calcification, Physiologic/drug effects
  • Calcium/pharmacology
  • Cattle
  • Chromatography, Liquid
  • Flavonoids/chemistry
  • Flavonoids/metabolism*
  • Flavonoids/pharmacology
  • Fluorescence
  • Gene Expression Profiling/methods*
  • Glycosides/chemistry
  • Glycosides/metabolism*
  • Imaging, Three-Dimensional/methods*
  • Inactivation, Metabolic/genetics
  • Larva/drug effects
  • Larva/genetics
  • Mass Spectrometry
  • Molecular Sequence Data
  • Organ Specificity/drug effects
  • Peptides/chemistry
  • Proteomics/methods*
  • Serum Albumin, Bovine/pharmacology
  • Spectrophotometry
  • Time Factors
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed
21445457 Full text @ Mol. Biosyst.
Abstract
Flavonoids isolated from Herba Epimedii such as icaritin, icariin and epimedin C have been suggested as potential bone anabolic compounds. However, the "specific localized effects" of these flavonoids in bone, in vivo, and the metabolism of these flavonoids in zebrafish larvae have never been demonstrated. In this study, we used multiple methods including in vivo imaging, drug metabolites profiling, transcriptomic and proteomic approaches to determine the mechanisms involved in the distribution and metabolism of the flavonoids in zebrafish larvae by measuring the fluorescence emission, in vivo, of icaritin and its glycoside derivatives. The fluorescence emission mechanism of icaritin in vitro was identified by spectrophotometric analysis, and the fluorescent property of icaritin was used as a probe to visualize the metabolism and distribution of icaritin and its glycoside derivatives in zebrafish larvae. Phase I and phase II metabolism of icaritin and its derivatives were identified in zebrafish by mass spectrometry. The combined transcriptomics and proteomics demonstrate a high degree of conservation of phase I and phase II drug metabolic enzymes between zebrafish larvae and mammals. Icaritin and its glycoside derivatives were demonstrated using combined approaches of in vivo imaging, drug metabolites identification, and transcriptomic and proteomic profiling to illustrate phase I and phase II metabolism of the flavonoids and their distribution in bone of zebrafish larvae. This study provides a new methodological model for use of the zebrafish larvae to examine drug metabolism.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping