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山奈酚 A 抗血管生成作用及其机制研究。

Anti-angiogenic effects and mechanisms of zerumin A from Alpinia caerulea.

机构信息

School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, PR China.

Chemodiversity Research Group, Department of Systematic and Evolutionary Botany, Faculty Centre of Biodiversity, University of Vienna, Austria.

出版信息

Food Chem. 2012 May 1;132(1):201-8. doi: 10.1016/j.foodchem.2011.10.057. Epub 2011 Oct 25.

DOI:10.1016/j.foodchem.2011.10.057
PMID:26434281
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.

摘要

蓝姜(Alpinia caerulea (R.Br.) Bentham),一种生长在澳大利亚热带和亚热带地区的多年生草本植物,被用作香料和姜的替代品。其果实被澳大利亚原住民用作传统食物;通过定量内源性碱性磷酸酶检测,对该植物的干燥果实、叶、根茎和根的 95%乙醇提取物进行了斑马鱼模型研究。只有果实提取物显示出潜在的抗血管生成作用,在 20μg/ml 时抑制血管形成 25%。分离并鉴定出两种二萜类化合物,分别为 zerumin A 和 (E)-8(17),12- 贝壳杉烯-15,16-二醛。Zerumin A 主要积累在果实中并带有羧基基团,可在野生型和 Tg(fli1a:EGFP)y1 斑马鱼胚胎中剂量依赖性地抑制血管形成。对野生型斑马鱼胚胎的半定量逆转录聚合酶链反应检测表明,zerumin A 影响与血管生成相关的多个分子靶点。通过人脐静脉内皮细胞检测的进一步研究表明,zerumin A 特异性抑制增殖和迁移步骤,以防止血管生成进展。

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