Oleuropein and Related Compounds Reduce Atherosclerosis

Abstract

Diabetes, obesity and metabolic syndrome all increase the risk for cardiovascular disease. Epidemilogic studies have demonstrated that a Mediterranean diet rich in olive oil is associated with decrease in risk for cardiovascular disease, obesity, and diabetes. Although some of the protection may be from the unsaturated fatty acid components of such a diet, additional small molecules found in olive oil and olive plants may cnfer protection, including the polyphenol oleuropein and hydroxytyrosol. We report here studies in mice that document the bioavailability of these molecules when administered orally. Using the apoE knockout mouse moel fed a high fat diet, we assessed the effects of orally administered oleuropein on diet-induced atherosclrerosis. Oleuropein significantly reduces the extent of atherosclerosis found in aorta of apoE knockout mice. Molecular modeling studies indicate that oleuropein binds to the peroxisome proliferator activating receptors (PPAR) alpha, gamma, and delta, but it does so with distinct conformations that differ from the way that PPAR alpha-, gamma-, and delta-specific agonists bind to their active sites. The manner with which oleuropein binds uniquely to the various PPARs offers a possible explanation for its effects on metabolism and cardiovascular disease.