Pentacyclic triterpenes from olive leaves formulated in micro-emulsion: characterization and role on de novo lipogenesis in HepG2 cells.

Olea europaea L. leaves contain a wide variety of pentacyclic triterpenes (TTPs). They have many pharmacological activities, but poor water solubility, permeability and bioavailability. A micro-emulsion (ME) loading a TTPs-enriched extract (EXT) was developed to improve these limits. Extract-loaded microemulsion (ME-EXT) was fully characterized. Stability study was carried out during 2 months at 4 °C and 25 °C. PAMPA (Parallel artificial membrane permeability assay) was used to evaluate the influence of the formulation on the intestinal passive permeability of TTPs. Furthermore, experiments were assayed on HepG2 cells to assess the effect of EXT and ME-EXT on de novo lipogenesis induced by elevated glucose levels. The effect was evaluated by detecting fatty acid synthase expression levels and intracellular lipid accumulation. EXT-ME resulted as homogeneous dispersed-phase droplets and it significantly increased EXT aqueous solubility. Physical and chemical analyses showed high stability of the formulation during 2 months. The formulation realized a prolonged release of TTPs and PAMPA permeation studies revealed that the formulation improve their passive permeability. Furthermore, EXT reduced lipid accumula-tion in HepG2 cells by inhibiting on de novo lipogenesis and ME-EXT formulation enhanced the inhibitory activity of EXT on intracellular lipid accumulation.