Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model.
Numerous clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO) that could protect and decrease the risk of developing Alzheimer's disease (AD). Moreover, recent studies have linked this protective effect to oleocanthal, a phenolic secoiridoid component of EVOO. This protective effect of oleocanthal against AD has been related to its ability to prevent amyloid-β (Aβ) and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type mice in vivo; however, its effect in a mouse model of AD is not known. In the current study, we investigated the effect of oleocanthal on pathological hallmarks of AD in TgSwDI, an animal model of AD. Mice treatment for 4 weeks with oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB). Further mechanistic studies demonstrated oleocanthal to increase the expression of important amyloid clearance proteins at the BBB including P-glycoprotein and LRP1, and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. The anti-inflammatory effect of oleocanthal in the brains of these mice was also obvious where it was able to reduce astrocytes activation and IL-1β levels. Finally, we could recapitulate the observed protective effect of oleocanthal in an in vitro human-based model, which could argue against species difference in response to oleocanthal. In conclusion, findings from in vivo and in vitro studies provide further support for the protective effect of oleocanthal against the progression of AD.
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.
Hisham
H
Qosa
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.
Yazan S
YS
Batarseh
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.
Mohamed M
MM
Mohyeldin
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.
Khalid A
KA
El Sayed
Pennington Biomedical Research Center, Louisiana State University , Baton Rouge, Louisiana 70803, United States.
Jeffrey N
JN
Keller
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.
Amal
A
Kaddoumi
D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000081004:Cyclopentane Monoterpenes; D004195:Disease Models, Animal; D008297:Male; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D000447:Aldehydes; D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D000081004:Cyclopentane Monoterpenes; D018696:Neuroprotective Agents; D047495:PPAR gamma; D010636:Phenols; D016875:tau Proteins; C577833:Abca1 protein, mouse; C558298:Mapt protein, mouse; C503534:oleocanthal
Alzheimer’s diseases; amyloid-β; blood-brain barrier; clearance; oleocanthal