British Journal of Nutrition

Metabolism and Metabolic Studies

Absorption and metabolism of olive oil secoiridoids in the small intestine

Joana Pintoa1a2, Fátima Paiva-Martinsa1, Giulia Coronaa2, Edward S. Debnama3, Maria Jose Oruna-Conchaa2, David Vauzoura2, Michael H. Gordona2 and Jeremy P. E. Spencera2 c1

a1 CIQ, Departamento de Química, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 687 Porto, Portugal

a2 Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, PO Box 226, Reading RG6 6AP, UK

a3 Department of Neuroscience, Physiology and Pharmacology, University College London, Royal Free Campus, London NW3 2PF, UK

Abstract

The secoiridoids 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (3,4-DHPEA-EDA) account for approximately 55 % of the phenolic content of olive oil and may be partly responsible for its reported human health benefits. We have investigated the absorption and metabolism of these secoiridoids in the upper gastrointestinal tract. Both 3,4-DHPEA-EDA and 3,4-DHPEA-EA were relatively stable under gastric conditions, only undergoing limited hydrolysis. Both secoiridoids were transferred across a human cellular model of the small intestine (Caco-2 cells). However, no glucuronide conjugation was observed for either secoiridoid during transfer, although some hydroxytyrosol and homovanillic alcohol were formed. As Caco-2 cells are known to express only limited metabolic activity, we also investigated the absorption and metabolism of secoiridoids in isolated, perfused segments of the jejunum and ileum. Here, both secoiridoids underwent extensive metabolism, most notably a two-electron reduction and glucuronidation during the transfer across both the ileum and jejunum. Unlike Caco-2 cells, the intact small-intestinal segments contain NADPH-dependent aldo-keto reductases, which reduce the aldehyde carbonyl group of 3,4-DHPEA-EA and one of the two aldeydic carbonyl groups present on 3,4-DHPEA-EDA. These reduced forms are then glucuronidated and represent the major in vivo small-intestinal metabolites of the secoiridoids. In agreement with the cell studies, perfusion of the jejunum and ileum also yielded hydroxytyrosol and homovanillic alcohol and their respective glucuronides. We suggest that the reduced and glucuronidated forms represent novel physiological metabolites of the secoiridoids that should be pursued in vivo and investigated for their biological activity.

(Received July 12 2010)

(Revised November 09 2010)

(Accepted November 16 2010)

(Online publication March 17 2011)

Correspondence:

c1 Corresponding author: Dr J. P. E. Spencer, email j.p.e.spencer@rdg.ac.uk

Footnotes

Abbreviations: 3,4-DHPEA-EA, 3,4-dihydroxyphenylethanol-elenolic acid; 3,4-DHPEA-EAH2, methyl 4-(2-(3,4-dihydroxyphenethoxy)-2-oxoethyl)-3-(hydroxymethyl)-2-methyl-3,4-dihydro-2H-pyran-5-carboxylate; 3,4-DHPEA-EDA, 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde; 3,4-DHPEA-EDAH2, 2-(3,4-dihydroxyphenyl)ethyl (4E)-4-formyl-3-(2-hydroxyethyl)hex-4-enoate; AP, apical; BA, basolateral; ECACC, European Collection of Cell Culture; HT, hydroxytyrosol; HVA, homovanillyl alcohol; LC, liquid chromatography; RT, retention time

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