title: Anti-angiogenic effects and mechanisms of zerumin A from Alpinia caerulea.
abstract: 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.
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: He
authors.affiliation: Chemodiversity Research Group, Department of Systematic and Evolutionary Botany, Faculty Centre of Biodiversity, University of Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Gilli
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
authors.forename: Grace Gar-Lee
authors.initials: GG
authors.lastname: Yue
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
authors.forename: Clara Bik-San
authors.initials: CB
authors.lastname: Lau
authors.affiliation: Chemodiversity Research Group, Department of Systematic and Evolutionary Botany, Faculty Centre of Biodiversity, University of Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Greger
authors.affiliation: Institute of Organic Chemistry, University of Vienna, Austria.
authors.forename: Lothar
authors.initials: L
authors.lastname: Brecker
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China. Electronic address: paulbut@hotmail.com.
authors.forename: Paul Pui-Hay
authors.initials: PP
authors.lastname: But
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D004224:Diterpenes
keywords: Alpinia caerulea; Anti-angiogenesis; HUVEC; Zebrafish; Zerumin A