Brain uptake of hydroxytyrosol and its main circulating metabolites: Protective potential in neuronal cells

Hydroxytyrosol (HT) and oleuropein derivatives are the main phenolic compounds in virgin olive oil (VOO). After VOO intake, HT is extensively metabolized being hydroxytyrosol-sulphate (HT-S) and hydroxytyrosol-acetate sulphate (HT-AC-S) the main circulating metabolites detected in human plasma. The brain uptake and accumulation of HT and its metabolites were observed after 21 days of rat diet supplementation (5 mg/kg rat/day) of HT in its native form or through oleuropein derivatives. To establish their neuroprotective potential HT-S and HT-AC-S were chemically synthetized and their protective effects against oxidative stress at physiological concentrations (10 μM) in neuroblastoma (SH-SY5Y) and dopaminergic (LUHMES) neuronal cells were observed. The sulpho-conjugated HT structures showed a lower protective effect than native HT. Results showed brain accumulation of HT and HT-S, suggesting their neuroprotective activity by the reduction of the oxidative stress at neuronal level.