Differential effects of oleuropein, a biophenol from Olea europaea, on anionic and zwiterionic phospholipid model membranes

Oleuropein (Ole) is the major phenolic constituent of the olive leaf (Olea europaea) and it is also present in olive oil and fruit. In the last years several compounds from olive tree, oleuropein among them, have shown a variety of biological activities such as antimicrobial or antioxidant. A phospholipid model membrane system was used to study whether the Ole biological effects could be membrane related. Ole showed a significant partition level in phospholipid membranes, i.e. 80%, at lipid-saturating conditions. Moreover, fluorescence quenching experiments indicated a shallow location for Ole in membranes. Ole promoted weak effects on zwiterionic phospholipids such as phosphatidylcholine or phosphatidylethanolamine. In contrast, differential scanning microcalorimetry, light scattering and fluorescence anisotropy pH titration studies revealed strong effects on anionic phospholipids such as phosphatidylglycerol at physiological pH and salt conditions. These effects consisted on perturbations at the phospholipid membrane surface, which might involve specific molecular interactions between Ole and the negatively charged phosphate group and therefore modify the phospholipid/water interface properties. It is proposed that Ole induces lipid structures similar to the gel-fluid intermediate phase (IP) described for PG membranes, in a similar way than low ionic strength does. These effects on phosphatidylglycerol may account for the antimicrobial activity of Ole.