The Olive Constituent Oleuropein Exhibits Anti-Ischemic, Antioxidative, and Hypolipidemic Effects in Anesthetized Rabbits

Abstract

Thgoal of this study was to evaluate the efficacy of the antioxidant olive constituent, oleuropein, on infarct size, oxidative damage, and the metabolic profile in rabbits subjected to ischemia. Oleuropein, 10 or 20 mg/(kg x d), was administered to 8 groups that consumed a normal or hypercholesterolemic diet for 6 wk or only the higher dose for 3 wk. Circulating levels of malondialdehyde, protein carbonyl, nitrite+nitrate, cholesterol, triglycerides, SOD activity, and the metabolic profile were measured using 1H NMR spectra. In rabbits that consumed the normal diet, the infarct size (percentage of infarct to risk areas) was reduced by the administration of 10 mg oleuropein/(kg x d) (16.1 +/- 2.9%) or 20 mg oleuropein/(kg x d) for 3 wk (21.7 +/- 2.2%) or for 6 wk (24.3 +/- 1.3%) compared with the control group (48.05 +/- 2.0%, P < 0.05). Only the higher dose of 20 mg/(kg x d) reduced the infarct size in hypercholesterolemic rabbits (34.7 +/- 4.4% for 6 wk and 34.8 +/- 6.1% for 3 wk) compared with the cholesterol-fed control group (52.8 +/- 2.4%, P < 0.05). Oleuropein decreased the plasma lipid peroxidation product and protein carbonyl concentrations compared with the control groups, in which these factors increased relative to baseline due to ischemia and reperfusion. Furthermore, in rabbits administered oleuropein, RBC superoxide dismutase activity did not change during ischemia and reperfusion. This activity was significantly higher than in both control groups in which it was reduced by ischemia and reperfusion compared with baseline. Treatment for 6 wk with both doses of oleuropein reduced total cholesterol and triglyceride concentrations. 1H NMR spectra revealed a different profile of glycolysis metabolites in the oleuropein-treated groups compared with the controls. Oleuropein, for 3 or 6 wk, reduced the infarct size, conferred strong antioxidant protection and reduced the circulating lipids. This is the first experimental study in vivo that suggests the possibility of using an olive constituent in the treatment of ischemia.

Oleuropein using as an Additive for Feed and Products used for Humans

“…In rat epithelial cells stimulated with cytokines, a concentrated polyphenol extract reduced nitrite concentration and free radical production. Rabbits with induced diabetes showed a decrease in oxidative stress markers when treated with oleuropein [37]. Other experiments support the antioxidant activity of the phenols oleuropein and hydroxytyrosol [59].…”

“…The cholesterol lowering effects of olive leaf extracts are thought to come from oleuropein, a substance contained within the leaf. Studies on hypercholesterolemic rats have shown that olive leaf extracts are more effective at lowering cholesterol than pure oleuropein [36,37,38].…”

Oleuropein as an inhibitor of peroxisome proliferator-activated receptor gamma

“…Oleuropein and other polyphenols from olive were studied, among others, for their ability to protect against metabolic syndrome, type 2 diabetes, cardiac ischemia, and other disorders, both in humans (de Bock et al 2013) and in experimental animal models (Andreadou et al 2006); (AlAzzawie and Alhamdani 2006); (Oi-Kano et al 2008). As it has been already reported, oleuropein suppressed adipogenesis in a dose-dependent manner in murine 3T3-L1 cell culture model (Drira et al 2011).…”

“…Beneficial effects of olive leaf extract have been described in vivo, including a reduction in adiposity and hyperlipidemia in dietary obese rat (Oi-Kano et al 2008), improvement of alloxan-induced diabetes in rabbits (Al-Azzawie and Alhamdani 2006) and improvement of insulin sensitivity in overweight humans (de Bock et al 2013). Purified oleuropein considerably reduced the infarct size in both normal and hypercholesterolemic rabbits that were subjected to ischemia/reperfusion, protected the reperfused myocardium from the oxidative damage and decreased total cholesterol and triglyceride levels (Andreadou et al 2006). In vitro, oleuropein reduced the expression of PPARc, inhibited adipogenesis and enhanced osteoblastogenesis in stem cells derived from human bone marrow (Santiago-Mora et al 2011).…”

Safety evaluation of subchronic oral administration of Oleuropein and its semisynthetic peracetylated derivative

“…Due to their health benefits, oleuropein, oleuropein derivatives, and seco-phenolic compounds are all considered to be important elements that make extra virgin olive oil a staple part of the Mediterranean diet. Also, the compounds include the ability to scavenge reactive oxygen species (ROS) [5][6][7] , to inhibit the proliferation of several tumor cell lines [5,[8][9][10][11] , and also to protect against cardiovascular diseases [3,[12][13][14][15] and metabolic disorders as Diabetes mellitus [16][17][18][19] . In addition, they are effective in experimental models of age-related disorders, such as neurodegenerative diseases [14,20,21] .…”