Anti-angiogenic effects and mechanisms of zerumin A from Alpinia caerulea
- Food Chem. 2012 May 1;132(1):201-8. doi: 10.1016/j.foodchem.2011.10.057.
- 1. School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
- 2. Chemodiversity Research Group, Department of Systematic and Evolutionary Botany, Faculty Centre of Biodiversity, University of Vienna, Austria.
- 3. Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
- 4. Institute of Organic Chemistry, University of Vienna, Austria.
- 5. School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China. Electronic address: [email protected].
Alpinia caerulea (R.Br.) Bentham, a perennial herb growing in tropical and subtropical Australia, is used as a flavouring spice and a ginger substitute. Its fruit has been used as indigenous food among the aboriginal Australians; 95% ethanol extracts of the dried fruits, leaves, rhizomes and roots of this plant were investigated in a zebrafish model by quantitative endogenous Alkaline Phosphatase assay. Only the fruit extract showed potential anti-angiogenic effect, inhibiting vessel formation by 25% at 20μg/ml. Two Diterpenoids were isolated and identified as zerumin A and (E)-8(17),12-labdadiene-15,16-dial. Zerumin A, which had mainly accumulated in the fruits and bearing a carboxylic group, could dose-dependently inhibit vessel formation, in both wild-type and Tg(fli1a:EGFP)y1 zebrafish embryos. The semi-quantitative reverse transcription polymerase chain reaction assay on wild type zebrafish embryos suggested that zerumin A affected multiple molecular targets related to angiogenesis. Further investigation, by human umbilical vein endothelial cell assays, revealed that zerumin A specifically inhibited the proliferation and migration steps, to prevent angiogenesis progress.