PUBLICATION
Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East african medicinal plants
- Authors
- Crawford, A.D., Liekens, S., Kamuhabwa, A.R., Maes, J., Munck, S., Busson, R., Rozenski, J., Esguerra, C.V., and de Witte, P.A.
- ID
- ZDB-PUB-110317-37
- Date
- 2011
- Source
- PLoS One 6(2): e14694 (Journal)
- Registered Authors
- Crawford, Alexander, Esguerra, Camila V.
- Keywords
- none
- MeSH Terms
-
- Abietanes/pharmacology
- Africa, Eastern
- Angiogenesis Inhibitors/isolation & purification*
- Angiogenesis Inhibitors/pharmacology
- Animals
- Animals, Genetically Modified
- Biological Assay/methods*
- Biological Products/isolation & purification*
- Biological Products/pharmacology
- Cells, Cultured
- Chick Embryo
- Coleus/chemistry
- Drug Discovery/methods*
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/drug effects
- Emodin/pharmacology
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Models, Biological
- Neovascularization, Physiologic/drug effects
- Neovascularization, Physiologic/physiology
- Plant Extracts/chemistry
- Plant Extracts/pharmacology
- Plants, Medicinal/chemistry*
- Zebrafish*/embryology
- Zebrafish*/physiology
- PubMed
- 21379387 Full text @ PLoS One
Citation
Crawford, A.D., Liekens, S., Kamuhabwa, A.R., Maes, J., Munck, S., Busson, R., Rozenski, J., Esguerra, C.V., and de Witte, P.A. (2011) Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East african medicinal plants. PLoS One. 6(2):e14694.
Abstract
Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC) and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS). Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping