Comparison of Oleocanthal-Low EVOO and Oleocanthal against Amyloid-β and Related Pathology in a Mouse Model of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is characterized by several pathological hallmarks, including the deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, blood-brain barrier (BBB) dysfunction, and neuroinflammation. Growing evidence support the neuroprotective effects of extra-virgin olive oil (EVOO) and oleocanthal (OC). In this work, we aimed to evaluate and compare the beneficial effects of equivalent doses of OC-low EVOO (0.5 mg total phenolic content/kg) and OC (0.5 mg OC/kg) on Aβ and related pathology and to assess their effect on neuroinflammation in a 5xFAD mouse model with advanced pathology. Homozygous 5xFAD mice were fed with refined olive oil (ROO), OC-low EVOO, or OC for 3 months starting at the age of 3 months. Our findings demonstrated that a low dose of 0.5 mg/kg EVOO-phenols and OC reduced brain Aβ levels and neuroinflammation by suppressing the nuclear factor-κB (NF-κB) pathway and reducing the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes. On the other hand, only OC suppressed the receptor for advanced glycation endproducts/high-mobility group box 1 (RAGE/HMGB1) pathway. In conclusion, our results indicated that while OC-low EVOO demonstrated a beneficial effect against Aβ-related pathology in 5xFAD mice, EVOO rich with OC could provide a higher anti-inflammatory effect by targeting multiple mechanisms. Collectively, diet supplementation with EVOO or OC could prevent, halt progression, and treat AD.

• Authors: Ihab M Abdallah, Kamal M Al-Shami, Amer E Alkhalifa, Nour F Al-Ghraiybah, Claudia Guillaume, Amal Kaddoumi
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 28 Issue 3 (Jan 27 2023) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 36770920 (Publication Type: Journal Article)

Chemical References

• Olive Oil
• oleocanthal
• Receptor for Advanced Glycation End Products
• Amyloid beta-Peptides
• Phenols

Topics

• Mice
• Animals
• Alzheimer Disease (drug therapy, metabolism)
• Olive Oil (pharmacology)
• Neuroinflammatory Diseases
• Receptor for Advanced Glycation End Products
• Mice, Inbred NOD
• Amyloid beta-Peptides (metabolism)
• Phenols (pharmacology, therapeutic use)