López-Yerena Anallely, Pérez Maria, Vallverdú-Queralt Anna, Miliarakis Eleftherios, Lamuela-Raventós Rosa M, Escribano-Ferrer Elvira
Department of Nutrition, Food Science and Gastronomy XaRTA, Faculty of Pharmacy and Food Sciences, Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona, 08028 Barcelona, Spain.
Laboratory of Organic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain.
Pharmaceutics. 2021 May 14;13(5):719. doi: 10.3390/pharmaceutics13050719.
Oleacein (OLEA) is one of the most important phenolic compounds in extra virgin olive oil in terms of concentration and health-promoting properties, yet there are insufficient data on its absorption and metabolism. Several non-human models have been developed to assess the intestinal permeability of drugs, among them, single-pass intestinal perfusion (SPIP), which is commonly used to investigate the trans-membrane transport of drugs in situ. In this study, the SPIP model and simultaneous luminal blood sampling were used to study the absorption and metabolism of OLEA in rats. Samples of intestinal fluid and mesenteric blood were taken at different times and the ileum segment was excised at the end of the experiment for analysis by LC-ESI-LTQ-Orbitrap-MS. OLEA was mostly metabolized by phase I reactions, undergoing hydrolysis and oxidation, and metabolite levels were much higher in the plasma than in the lumen. The large number of metabolites identified and their relatively high abundance indicates an important intestinal first-pass effect during absorption. According to the results, OLEA is well absorbed in the intestine, with an intestinal permeability similar to that of the highly permeable model compound naproxen. No significant differences were found in the percentage of absorbed OLEA and naproxen (48.98 ± 12.27% and 43.96 ± 7.58%, respectively).
油橄榄苦素（OLEA）是特级初榨橄榄油中含量最高且具有促进健康特性的重要酚类化合物之一，但关于其吸收和代谢的数据却并不充分。已经开发了几种非人类模型来评估药物的肠道通透性，其中单通道肠道灌注（SPIP）常用于原位研究药物的跨膜转运。在本研究中，采用SPIP模型和同时进行的肠腔血液采样来研究大鼠体内OLEA的吸收和代谢。在不同时间采集肠液和肠系膜血液样本，并在实验结束时切除回肠段，通过液相色谱-电喷雾电离-线性离子阱-轨道阱质谱（LC-ESI-LTQ-Orbitrap-MS）进行分析。OLEA大多通过I相反应进行代谢，经历水解和氧化，血浆中的代谢物水平远高于肠腔中的水平。鉴定出的大量代谢物及其相对较高的丰度表明在吸收过程中存在重要的肠道首过效应。根据结果，OLEA在肠道中吸收良好，其肠道通透性与高通透性模型化合物萘普生相似。吸收的OLEA和萘普生的百分比未发现显著差异（分别为48.98±12.27%和43.96±7.58%）。
