Olive-Oil-Derived Oleocanthal Enhances β-AmyloidClearance as a Potential Neuroprotective Mechanism against Alzheimer’sDisease: In Vitro and in Vivo Studies

摘要

Oleocanthal, a phenolic component of extra-virgin olive oil, has been recently linked to reduced risk of Alzheimer’s disease (AD), a neurodegenerative disease that is characterized by accumulation of β-amyloid (Aβ) and tau proteins in the brain. However, the mechanism by which oleocanthal exerts its neuroprotective effect is still incompletely understood. Here, we provide in vitro and in vivo evidence for the potential of oleocanthal to enhance Aβ clearance from the brain via up-regulation of P-glycoprotein (P-gp) and LDL lipoprotein receptor related protein-1 (LRP1), major Aβ transport proteins, at the blood-brain barrier (BBB). Results from in vitro and in vivo studies demonstrated similar and consistent pattern of oleocanthal in controlling Aβ levels. In cultured mice brain endothelial cells, oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of ¹²⁵I-Aβ40 showed that administration of oleocanthal extracted from extra-virgin olive oil to C57BL/6 wild-type mice enhanced ¹²⁵I-Aβ40 clearance fromthe brain and increased the BEI% from 62.0 ± 3.0% for controlmice to 79.9 ± 1.6% for oleocanthal treated mice. Increased P-gpand LRP1 expression in the brain microvessels and inhibition studiesconfirmed the role of up-regulation of these proteins in enhancing ¹²⁵I-Aβ40 clearance after oleocanthal treatment.Furthermore, our results demonstrated significant increase in ¹²⁵I-Aβ40 degradation as a result of the up-regulationof Aβ degrading enzymes following oleocanthal treatment. Inconclusion, these findings provide experimental support that potentialreduced risk of AD associated with extra-virgin olive oil could bemediated by enhancement of Aβ clearance from the brain.