Keiler Annekathrin Martina, Djiogue Sefirin, Ehrhardt Tino, Zierau Oliver, Skaltsounis Leandros, Halabalaki Maria, Vollmer Günter
Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany.
Department of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon.
Planta Med. 2015 Sep;81(14):1263-9. doi: 10.1055/s-0035-1546194. Epub 2015 Jul 10.
Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes.
油橄榄苦素是一种来自橄榄油的生物活性化合物。它因其具有抗炎、抗增殖作用，且已在体外和体内显示出神经保护特性而备受关注。鉴于其多酚结构，本研究旨在表征油橄榄苦素的雌激素特性。这可能有助于部分解释地中海饮食所具有的有益作用。通过不同方法评估了油橄榄苦素的雌激素特性：a）在表达雌激素受体α或β的MVLN或RNDA细胞中刺激报告基因活性；b）在表达雌激素受体α或β的U2OS骨肉瘤细胞中刺激荧光素酶报告基因活性；c）阐明对转导了两种雌激素受体的U2OS细胞中雌二醇诱导的基因表达的影响。根据细胞系来源，油橄榄苦素在U2OS -雌激素受体α细胞中抑制荧光素酶活性（MVLN、U2OS -雌激素受体β），或在10μM时微弱诱导报告基因活性。然而，油橄榄苦素抑制来自两种雌激素受体的雌二醇对荧光素酶活性的刺激。单独给予油橄榄苦素时，它不会刺激U2OS细胞中的基因表达，但它能显著调节雌二醇的反应。油橄榄苦素增强了雌二醇对那些被认为通过异二聚体雌激素受体调节的基因的调控作用。由于油橄榄苦素的雌激素反应模式相当独特，我们将其结果与橄榄苦苷的结果进行了比较。油橄榄苦素与两种雌激素受体结合，根据细胞系诱导出雌二醇激动或拮抗作用。关于U2OS -雌激素受体α/β细胞中的基因表达调控，油橄榄苦素和橄榄苦苷增强了雌二醇介导的对异二聚体调控基因的调控作用。
