Effects of verbascoside, a phenylpropanoid glycoside from lemon verbena, on phospholipid model membranes

Phenylpropanoid glycosides are water-soluble compounds widely distributed, most of them deriving from medicinal herbs. Among them, verbascoside or acteoside has exhibited a wide biological activity, being free radical scavenging the most representative one. Moreover, antitumor, antimicrobial, anti-inflammatory, anti-thrombotic and wound healing properties have been previously described. Herein, the interaction of verbascoside with phospholipid membranes has been studied by means of differential scanning calorimetry, fluorescence anisotropy and dynamic light scattering. Verbascoside showed stronger affinity for negatively charged membranes composed of phosphatidylglycerol (PG) than for phosphatidylcholine (PC) membranes. This compound promoted phase separation of lipid domains in PC membranes and formed a stable lipid complex with and approximate phospholipid/verbascoside ratio of 4:1. Despite its hydrophilic character, verbascoside's caffeoyl moiety was located deep into the hydrophobic core of PC membranes and was almost inaccessible to spin probes located at different depths in PG membranes. This compound affected the ionization behavior of the PG phosphate group and most likely interacted with the vesicles surface. The presence of verbascoside decreased the particle size in PG unilamellar vesicles through the increase of the phospholipid head group area. A localization of verbascoside filling the upper region of PG bilayers close to the phospholipid/water interface is proposed. These effects on membranes may help to understand the mechanism of the biological activity of verbascoside and other similar phenylpropanoid glycosides.