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Neuroprotective effects of olive-phenolics

Neuroprotective effects of olive-phenolics

The olive tree provides us with numerous bioactive compounds, mainly biophenols, found primarily in olive fruit, oil, and leaves. Olive biophenols are known for their biological activities in preventing diseases and maintaining health; they provide neuroprotection and could play a role in slowing cognitive dysfunction and the neurodegenerative process in conditions such as Alzheimer’s disease (AD)1.

Several biophenols have been extracted from olive products (fruits, oil, and leaves) and researched for their neuroprotection effect. Examples of olive-biophenols include oleocanthal, hydroxytyrosol, oleuropein, hydroxy oleocanthal (oleacin), and tyrosol; and the first three in the list are the most studied biophenols for their health-promoting properties. 

Neuroprotective effect of phenolic compounds in extra virgin olive oil (EVOO)

EVOO is defined as high-quality olive oil obtained from the first pressing of olive fruit by purely mechanical means. The phenolic fraction represents about 5% in olive oil with estimated average total phenolic content of 500 mg/kg. Oleocanthal (OC) is one of the most studied biophenols in EVOO, either as pure OC or OC-rich EVOO, for its neuroprotection effect2.  The content of OC in EVOO is highly variable, ranging from null up to 1500 mg/kg oil. Many factors determine the OC amount in the oil, including oil processing and purification. OC possesses anti-inflammatory and antioxidant properties similar to the non-steroidal anti-inflammatory drug ibuprofen. Our preclinical research in AD mouse models demonstrated that OC and OC-rich EVOO significantly reduced pathological hallmarks of AD, such as brain amyloid plaques, hyperphosphorylated tau, neuroinflammation, and oxidative stress. In addition, OC and OC-rich EVOO improved the cerebrovascular and memory functions in the mice. According to our findings and others, OC exerts its effect via inhibiting cyclooxygenase and NLRP3 inflammasomes activation by inhibiting the transcription factor NFκB pathway and the induction of autophagy through the AMPK/ULK1 pathway3-7.

Hydroxytyrosol is another biophenol studied for its neuroprotection effect.  Olive oil-derived hydroxytyrosol demonstrated antioxidant and anti-inflammatory effects against neurodegenerative diseases, including Parkinson’s disease and AD. During oxidative stress, hydroxytyrosol acts as a scavenger of reactive free radicals and induces antioxidant enzymes by activating transcription factor Nrf28,9.

Neuroprotective effect of phenolic compounds in olive leaves

Biophenols content in olive leaves is higher than that in EVOO, representing up to 2% of total phenols on a fresh weight basis. Oleuropein, an ester of hydroxytyrosol with the oleoside skeleton, accounts for about 25% of the total biophenols in the olive leaf. Oleuropein possesses most of the health-promoting properties of olive leaves. The glycosylated form of oleuropein gives rise to many compounds found in olive fruit and leaves via aglycon through the opening of the elenolic acid ring. Its quantity is meager in olive oil compared to olive leaves because of its extensive enzymatic degradation during oil extraction and low partitioning in oil. During the extraction process, glycosylated oleuropein is hydrolyzed to several compounds, including hydroxytyrosol, elenolic acid, and oleuropein aglycone, which could also be detected in olive oil.

Oleuropein has been observed to exert various neuroprotective effects with antioxidant and anti-inflammatory properties. The neuroprotective effect of oleuropein is extensively evaluated and tested in animal models of different brain diseases, including AD, Parkinson’s disease, cerebral stroke, anxiety, epilepsy, and depression. Oleuropein has been reported to interfere with prions aggregation, such as amyloid and tau in AD and α-synuclein in Parkinson’s disease. In addition, studies have shown that oleuropein reduces neuronal apoptosis, increases cerebrovascular function, and improves memory10.

Several mechanisms exert the antioxidant and anti-inflammatory effects of oleuropein. Findings from our research demonstrated that oleuropein reduced neuroinflammation by inhibiting the NF-κB pathway and suppressing the activation of NLRP3 inflammasomes and RAGE/HMGB1 pathways11. Other mechanisms include the activation of the Nrf−2/heme oxygenase-1 pathway, which also contributes to oleuropein’s anti-inflammatory and antioxidant properties12.


In summary, olive phenolics possess various health benefits, including their neuroprotection effect supported by research. Until we better understand the individual phenol’s dose-response effect against brain diseases, the dietary consumption of natural olive resources such as olive fruit, olive oil, and olive leaves is the best approach for a healthy brain and healthy body.

View article references

  1. Angeloni C, Malaguti M, Barbalace MC, Hrelia S. Bioactivity of Olive Oil Phenols in Neuroprotection. Int J Mol Sci. 2017;18(11):2230.
  2. Pang KL, Chin KY. The Biological activities of oleocanthal from a molecular perspective. Nutrients. 2018;10(5):570.
  3. Al Rihani SB, Darakjian LI, Kaddoumi A. Oleocanthal-rich extra-virgin olive oil restores the blood-brain barrier function through NLRP3 inflammasome inhibition simultaneously with autophagy induction in TgSwDI mice. ACS Chem. Neurosci. 2019;10(8):3543-3554.
  4. Batarseh YS, Kaddoumi A. Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer's disease. J Nutr. Biochem. 2018;55:113-123.
  5. Batarseh YS, Mohamed LA, Al Rihani SB, Mousa YM, Siddique AB, El Sayed KA, Kaddoumi A. Oleocanthal ameliorates amyloid-β oligomers' toxicity on astrocytes and neuronal cells: In vitro studies. Neuroscience. 2017;352:204-215.
  6. Qosa H, Batarseh YS, Mohyeldin MM, El Sayed KA, Keller JN, Kaddoumi A. 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):1849-1859.
  7. Qosa H, Mohamed LA, Batarseh YS, Alqahtani S, Ibrahim B, LeVine H 3rd, Keller JN, Kaddoumi A. Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of TgSwDI mice. J Nutr Biochem. 2015;26(12):1479-1490.
  8. Liu Z, Cai W, Lang M, Yan R, Li Z, Zhang G, Yu P, Wang Y, Sun Y, Zhang Z. Neuroprotective effects and mechanisms of action of multifunctional agents targeting free radicals, monoamine oxidase B and cholinesterase in Parkinson's disease model. J Mol Neurosci. 2017;61(4):498-510.
  9. Peng S, Zhang B, Yao J, Duan D, Fang J. Dual protection of hydroxytyrosol, an olive oil polyphenol, against oxidative damage in PC12 cells. Food Funct. 2015;6(6):2091-100.
  10. Ontario ML, Siracusa R, Modafferi S, Scuto M, Sciuto S, Greco V, Bertuccio MP, Trovato Salinaro A, Crea R, Calabrese EJ, Di Paola R, Calabrese V. Potential prevention and treatment of neurodegenerative disorders by olive polyphenols and hidrox. Mech Ageing Dev. 2022;203:111637.
  11. Abdallah IM, Al-Shami KM, Yang E, Wang J, Guillaume C, Kaddoumi A. Oleuropein-rich olive leaf extract attenuates neuroinflammation in the Alzheimer's disease mouse model. ACS Chem. Neurosci. 2022;13(7):1002-1013.
  12. Parzonko A, Czerwińska ME, Kiss AK, Naruszewicz M. Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2/heme oxygenase-1 pathway. Phytomedicine. 2013;20(12):1088-94.