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Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model.
ACS Chem Neurosci 2015; 6(11):1849-59AC

Abstract

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.

Authors+Show Affiliations

Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.Pennington Biomedical Research Center, Louisiana State University , Baton Rouge, Louisiana 70803, United States.Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe , Monroe, Louisiana 71201, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26348065

Citation

Qosa, Hisham, et al. "Oleocanthal Enhances Amyloid-β Clearance From the Brains of TgSwDI Mice and in Vitro Across a Human Blood-brain Barrier Model." ACS Chemical Neuroscience, vol. 6, no. 11, 2015, pp. 1849-59.
Qosa H, Batarseh YS, Mohyeldin MM, et al. Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model. ACS Chem Neurosci. 2015;6(11):1849-59.
Qosa, H., Batarseh, Y. S., Mohyeldin, M. M., El Sayed, K. A., Keller, J. N., & Kaddoumi, A. (2015). Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model. ACS Chemical Neuroscience, 6(11), pp. 1849-59. doi:10.1021/acschemneuro.5b00190.
Qosa H, et al. Oleocanthal Enhances Amyloid-β Clearance From the Brains of TgSwDI Mice and in Vitro Across a Human Blood-brain Barrier Model. ACS Chem Neurosci. 2015 Nov 18;6(11):1849-59. PubMed PMID: 26348065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model. AU - Qosa,Hisham, AU - Batarseh,Yazan S, AU - Mohyeldin,Mohamed M, AU - El Sayed,Khalid A, AU - Keller,Jeffrey N, AU - Kaddoumi,Amal, Y1 - 2015/09/16/ PY - 2015/9/9/entrez PY - 2015/9/9/pubmed PY - 2016/8/31/medline KW - Alzheimer’s diseases KW - amyloid-β KW - blood-brain barrier KW - clearance KW - oleocanthal SP - 1849 EP - 59 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 6 IS - 11 N2 - 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. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/26348065/Oleocanthal_enhances_amyloid_β_clearance_from_the_brains_of_TgSwDI_mice_and_in_vitro_across_a_human_blood_brain_barrier_model_ L2 - https://dx.doi.org/10.1021/acschemneuro.5b00190 DB - PRIME DP - Unbound Medicine ER -