Insights into the Antioxidant/Antiradical Effects and In Vitro Intestinal Permeation of Oleocanthal and Its Metabolites Tyrosol and Oleocanthalic Acid.

(1) Background: In recent years, numerous studies have highlighted the beneficial effects of extra virgin olive oil (EVOO) as an active ingredient against chronic diseases. The properties of EVOO are due to its peculiar composition, mainly to its rich content of polyphenols. In fact, polyphenols may contribute to counteract oxidative stress, which often accompanies chronic diseases. In this work, the antioxidant effects of high-value polyphenol oleocanthal (OC) and its main metabolites, tyrosol (Tyr) and oleocanthalic acid (OA), respectively, have been investigated along with their impact on cell viability. (2) Methods: OC, Tyr, and OA have been evaluated regarding antiradical properties in term of scavenging capacity towards biologically relevant reactive species, including O2●-, HOCl, and ROO●, as well as their antioxidant/antiradical capacity (FRAP, DPPH●, ABTS●+). Moreover, the ability to permeate the intestinal membrane was assessed by an intestinal co-culture model composed by Caco-2 and HT29-MTX cell lines. (3) Results: The capacity of OC and Tyr as radical oxygen species (ROS) scavengers, particularly regarding HOCl and O2●-, was clearly demonstrated. Furthermore, the ability to permeate the intestinal co-culture model was plainly proved by the good permeations (>50%) achieved by all compounds. (4) Conclusions: OC, OA, and Tyr revealed promising properties against oxidative diseases.

Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation.

Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration.

Content Variations in Oleocanthalic Acid and Other Phenolic Compounds in Extra-Virgin Olive Oil during Storage.

The health benefits of extra-virgin olive oil (EVOO) are strictly linked to the presence of phenolic compounds, which exhibit numerous nutraceutical properties. In EVOO, the most important class of phenolic compounds is represented by secoiridoids (oleacein and oleocanthal). EVOO is constantly subjected to degradation processes, including hydrolytic and oxidative reactions that influence its phenolic composition. In particular, the hydrolytic reactions determine the transformation of oleocanthal and oleacein into the corresponding phenyl-alcohols, tyrosol, and hydroxytyrosol. Furthermore, oleocanthal by oxidation processes can be converted to oleocanthalic acid. In this study, we evaluated the phenolic composition of three EVOO samples kept at different storage conditions for 15 months, focusing on the variation of oleocanthalic acid content. Specifically, the samples were stored at 4 °C in darkness and at 25 °C with light exposure. The results of our analyses highlighted that in EVOOs exposed to light and maintained at 25 °C, the degradation was more marked than in EVOO stored in dark and at 4 °C, due to the greater influence of external factors on storage conditions. Although chemical-physical characteristics of EVOOs are slightly different depending on provenience and treatment time, the results of this study reveal that storage conditions are fundamental to controlling phenol concentration.

The decrease in the health benefits of extra virgin olive oil during storage is conditioned by the initial phenolic profile.

Phenols are responsible for the only health claim of virgin olive oil (VOO) recognized by the European Commission EU 432/2012 and the European Food Safety Authority. In this research, we studied the decrease in the phenolic content of 160 extra VOOs (EVOOs) after 12 months storage in darkness at 20 °C. Phenolic concentration was decreased 42.0 ± 24.3% after this period and this reduction strongly depended on the initial phenolic profile. Hence, EVOOs with predominance in oleacein and oleocanthal experienced a larger decrease in phenolic content than oils enriched in other phenols. Complementarily, hydroxytyrosol and oleocanthalic acid increased significantly in aged EVOOs, which allowed their discrimination from recently produced EVOOs. These changes are explained by degradation of main secoiridoids during storage due to their antioxidant properties. Hydroxytyrosol and oleocanthalic acid can be considered markers of olive oil ageing, although they can also provide information about quality or stability.

Oleocanthalic Acid, a Chemical Marker of Olive Oil Aging and Exposure to a High Storage Temperature with Potential Neuroprotective Activity.

The investigation of olive oils stored for a period of 24 months under appropriate conditions (25 °C, dark place, and airtight container) led to the identification of a new major phenolic ingredient, which was named oleocanthalic acid. The structure of the new compound was elucidated using one- and two-dimensional nuclear magnetic resonance in combination with tandem mass spectrometry. The new compound is an oxidation product of oleocanthal and is found in fresh oils in very low concentrations. The concentration of oleocanthalic acid increased with storage time, while the oleocanthal concentration decreased. A similar increase of the oleocanthalic acid/oleocanthal ratio was achieved after exposure of olive oil to 60 °C for 14 days. Although the presence of an oxidized derivative of decarboxymethylated ligstroside aglycon had been reported, it is the first time that its structure is characterized. The isolated compound could induce the expression of amyloid-ß major transport proteins as well as tight junctions expressed at the blood-brain barrier, suggesting that oleocanthalic acid could be beneficial against Alzheimer's disease.