Crossing and metabolism of tyrosol and hydroxytyrosol by implementing an in vitro blood-brain barrier model of human primary cells

Fuente: PubMed "olive oil"
Food Funct. 2026 Mar 31. doi: 10.1039/d6fo00323k. Online ahead of print.ABSTRACTThere is mounting evidence that the neuroprotective benefits associated with olive oil consumption are related to the presence of the phenolic alcohols tyrosol (Tyr) and hydroxytyrosol (HT). In vitro blood-brain barrier (BBB) models are considered indispensable platforms for the mechanistic assessment of compound permeability. However, it is important to note that most of these models offer only a limited representation of BBB physiology. The aim of the present study was to develop a human triculture (human brain microvascular endothelial cells (HBMECs), astrocytes and pericytes) BBB model to evaluate the permeability of dietary bioactives. In particular, the crossing of Tyr and HT through the BBB and the BBB's potential to further metabolize these bioactives were evaluated. Different seeding densities of HBMECs and the presence/absence of fibronectin as extracellular matrix were considered. 1 × 105 cells and fibronectin coating of the apical transwell surface yielded higher TEER values and improved barrier integrity. Immunocytochemical analysis further confirmed the well-defined ZO-1 localisation at the cell-cell junctions. After 96 h of the establishment of the triculture, the human-origin BBB (ho-BBB) model presented the optimal barrier conditions for the execution of permeability studies. The transport of Tyr and HT (at two different concentrations, 1 and 10 µM) across the ho-BBB was evaluated by UPLC-MS/MS. Our results proved that the ho-BBB was more permeable to HT (high permeability) than Tyr (medium permeability), as determined by calculating transport percentages and apparent permeability coefficients (Papp). This study provides the first evidence that HBMECs can metabolize HT, transforming it into HT-3'-sulfate and HT-4'-sulfate.PMID:41914719 | DOI:10.1039/d6fo00323k