Hydroxytyrosol is a phenolic compound present in extra virgin olive oil, either in free form or as derivatives, and related to some of the health benefits described for olive oil intake. We have demonstrated previously that hydroxytyrosol inhibits angiogenesis both in vitro and in vivo. In the present study, we evaluate the anti-angiogenic potential of five hydroxytyrosol derivatives. Three of these derivatives contain a nitro group and they exhibit a much weaker effect than hydroxytyrosol in the tubule formation assay on Matrigel and therefore were not studied further. In contrast, both hydroxytyrosyl acetate and ethyl hydroxytyrosyl ether show more potent inhibitory effects than hydroxytyrosol in both the in vitro tubule formation assay on Matrigel and the in vivo chorioallantoic membrane assay. Additionally, these three compounds had slight pro-apoptotic effects and decreased matrix metalloproteinase-2 levels in cell extracts.

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羟基酪醇和五种衍生物抗血管生成潜力的比较

羟基酪醇是一种以游离形式或衍生物形式存在于特级初榨橄榄油中的酚类化合物，与上述橄榄油摄入所带来的一些健康益处有关。我们以前已经证明了羟基酪醇在体外和体内均抑制血管生成。在本研究中，我们评估了五种羟基酪醇衍生物的抗血管生成潜力。这些衍生物中的三个含有一个硝基，在对Matrigel进行小管形成实验中，它们的表现比羟基酪醇弱得多，因此不再进行进一步研究。相比之下，在对Matrigel进行体外肾小管形成试验和对羟基苯甲酸酯进行体外肾小管形成试验中，乙酸羟基酪氨酯和乙基羟基酪氨醚均显示出比羟基酪醇更强的抑制作用。体内绒膜尿囊膜测定。此外，这三种化合物具有轻微的促凋亡作用，并降低了细胞提取物中基质金属蛋白酶2的水平。