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Planta Med 2015; 81(08): 655-663
DOI: 10.1055/s-0034-1383306
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

The Natural Olive Constituent Oleuropein Induces Nutritional Cardioprotection in Normal and Cholesterol-Fed Rabbits: Comparison with Preconditioning

Ioanna Andreadou
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Dimitra Benaki
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Panagiotis Efentakis
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Sofia-Iris Bibli
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Alkistis-Ioanna Milioni
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Anastasia Papachristodoulou
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Anastasia Zoga
2   Second Department of Cardiology, University of Athens Medical School, Attikon University Hospital, Athens, Greece
,
Alexios-Leandros Skaltsounis
3   Laboratory of Pharmacognosy and Chemistry of Natural Products, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Emmanuel Mikros
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Athens, Athens, Greece
,
Efstathios K. Iliodromitis
2   Second Department of Cardiology, University of Athens Medical School, Attikon University Hospital, Athens, Greece
› Author Affiliations
Further Information

Publication History

received 01 August 2014
revised 01 October 2014

accepted 15 October 2014

Publication Date:
04 December 2014 (online)

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Abstract

Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg−1 × day−1. All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing preconditioning-involved signaling transduction. Nutritional preconditioning may support the low cardiovascular morbidity and mortality associated with the consumption of olive products.

Key words

Olea europaea - Oleaceae - oleuropein - preconditioning - oxidative stress - signaling molecules - metabonomics

Supporting Information

 

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