PUBLICATION

Anti-angiogenic Activity and Mechanism of Sesquiterpene Lactones from Centipeda minima

Authors
Huang, W., Yu, X., Liang, N., Ge, W., Kwok, H.F., Lau, C.B., Li, Y., Chung, H.Y.
ID
ZDB-PUB-160712-7
Date
2016
Source
Natural Product Communications   11: 435-8 (Journal)
Registered Authors
Ge, Wei
Keywords
none
MeSH Terms
  • Angiogenesis Inhibitors/analysis*
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Asteraceae/chemistry*
  • Drugs, Chinese Herbal/chemistry
  • Drugs, Chinese Herbal/pharmacology
  • Lactones/isolation & purification*
  • Lactones/pharmacology*
  • Sesquiterpenes/isolation & purification*
  • Sesquiterpenes/pharmacology*
  • Zebrafish
PubMed
27396185
Abstract
Centipeda minima is a Chinese herbal medicine used in the treatment of various diseases including cancer. An ethanol extract of the herb, its four fractions with different polarities, and two volatile oils prepared by steam distillation (SD) and supercritical fluid extraction (SFE) were investigated for their anti-angiogenic activity in a wild-type zebrafish model using a quantitative endogenous alkaline phosphatase (EAP) assay. The SFE oil displayed potent anti-angiogenic activity. Fifteen sesquiterpene lactones (SLs; compounds 1-15) isolated from the SFE oil were evaluated for their anti-angiogenic effect. Results revealed that pseudoguaianolide type SLs (1-8) inhibited vessel formation in the zebrafish embryos while guaianolide type SLs (9-15) showed little effect. Among the active ones, 6-O-angeloylenolin (1), a major component of SFE oil, possessed the strongest effect by reducing vessel formation in zebrafish embryos to 40% of the control value at 29.7 µM. Further study using the Tg (fli1a:EGFP) y1-type zebrafish model revealed that it blocked both intersegmental blood vessels (ISVs) and subintestinal vessels plexus (SIVs) formation in zebrafish embryos. Real-time polymerase chain reaction assay on the wild-type zebrafish embryos suggested that 6-O-angeloylenolin affected multiple molecular targets related to angiogenesis including VEGF receptor, angiopoietin, and its receptors. Taken together, our findings demonstrate that C. minima possesses anti-angiogenic activity, and 6-O-angeloylenolin is a promising candidate for the development of an anti-angiogenic agent.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping