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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. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet is linked to various health benefits, especially the consumption of olive oil as a key component. Multiple studies highlight its advantages, particularly due to its fatty acid composition and additional components like phenolic compounds. A significant antioxidant compound, oleocanthal, known for its antioxidant properties, has gained attention in the pharmaceutical industry for its anti-inflammatory and antiproliferative effects. It shows promise in addressing cardiovascular diseases, metabolic syndrome, and neuroprotection. This systematic review aims to evaluate the existing literature on oleocanthal, examining its role in biological processes and potential impact on conditions like inflammation and cancer. Methods: We performed several searches in PubMed (MEDLINE), Web of Science (WOS), and Cochrane based on the terms "Oleocanthal", "Cancer", and "Inflammation". The inclusion criteria were as follows: studies whose main topics were oleocanthal and cancer or inflammation. On the other hand, the exclusion criteria were studies that were not focused on oleocanthal, reviews, or editorial material. Given that these findings are explanatory rather than derived from clinical trials, we refrained from employing methods to assess potential bias. This systematic review did not receive any external funding. Results: We found 174 records from these searches, where we discarded reviews and editorial material, duplicated articles, and 1 retracted article. Finally, we had 53 reports assessed for eligibility that were included in this review. Discussion: OC exhibits promising therapeutic potential against both inflammation and cancer. We addressed its ability to target inflammatory genes and pathways, offering potential treatments for conditions like rheumatic diseases by regulating pathways such as NF-kB and MAPK. Additionally, OC's anticancer properties, particularly its notable inhibition of c-Met signaling across various cancers, highlight its efficacy, showcasing promise as a potential treatment. [ABSTRACT FROM AUTHOR]

Oleocanthal, a minor polar compound in extra-virgin olive (EVO) oil, contains anticancer properties, which should be encouraged in its use in oncology. Gastric Cancer (GC), a very aggressive human cancer, is often diagnosed at advanced stages, when surgery is substituted or supported by chemotherapy (CT). However, CT frequently fails due to the patient's resistance to the treatment. Thus, the aim of this study is to verify whether an OC-enriched EVO oil extract fraction (OCF) may be useful in order to overcome a resistance to GC. We evaluated the OCF effects on an AGS gastric adenocarcinoma cell line wild type (AGS wt) and on its subpopulations resistant to 5-fluorouracil (5FUr), Paclitaxel (TAXr) or cisplatin (CISr). We found that a 60 µM dose of the OCF acts on the AGS wt, 5FUr and TAXr, leading to the cell cycle inhibition and to a ROS production, but not on CISr cells. Resistance of CISr to the OCF seems to be due to higher levels of antioxidant-enzymes that can counteract the OCF-induced ROS production. Moreover, using the OCF plus 5-fluorouracil, Paclitaxel or cisplatin, we found a potentiating effect compared with a mono-treatment in all resistant GC cells, including CISr. In conclusion, the use of the OCF in the management of GC has shown very interesting advantages, opening-up the possibility to evaluate the efficacy of the OCF in vivo, as a valid adjuvant in the treatment of resistant GC. [ABSTRACT FROM AUTHOR]

The health, therapeutic, and organoleptic characteristics of olive oil depend on functional bioactive compounds, such as phenols, tocopherols, squalene, and sterols. Genotype plays a key role in the diversity and concentration of secondary compounds peculiar to olive. In this study, the most important bioactive compounds of olive fruit were studied in numerous international olive cultivars during two consecutive seasons. A large variability was measured for each studied metabolite in all 61 olive cultivars. Total phenol content varied on a scale of 1–10 (3831–39,252 mg kg−1) in the studied cultivars. Squalene values fluctuated over an even wider range (1–15), with values of 274 to 4351 mg kg−1. Total sterols ranged from 119 to 969 mg kg−1, and total tocopherols varied from 135 to 579 mg kg−1 in fruit pulp. In the present study, the linkage among the most important quality traits highlighted the scarcity of cultivars with high content of at least three traits together. This work provided sound information on the fruit metabolite profile of a wide range of cultivars, which will facilitate the studies on the genomic regulation of plant metabolites and development of new olive genotypes through genomics-assisted breeding. [ABSTRACT FROM AUTHOR]

The antioxidant and anti-inflammatory responses of (−)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulation of histones were studied. Met-OLE inhibited LPS-induced intracellular reactive oxygen species (ROS) and nitrite (NO) production and decreased the overexpression of the pro-inflammatory enzymes COX-2, mPGES-1 and iNOS in murine macrophages. In addition, met-OLE was able to significantly decrease the activation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs) and blocked canonical and non-canonical inflammasome signaling pathways. On the contrary, met-OLE upregulated haem oxigenase 1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) expression in treated cells. Finally, met-OLE pretreated spleen cells counteracted LPS induction, preventing H3K18 acetylation or H3K9 and H3K27 demethylation. Overall, these results provide novel mechanistic insights into the beneficial effects of met-OLE regarding the regulation of the immune–inflammatory response through epigenetic changes in histone markers. This revealing evidence suggests that the methylated metabolite of OLE may contribute significantly to the beneficial effects that are associated with the secoiridoid-related compound and the usual consumption of EVOO. [ABSTRACT FROM AUTHOR]

The ancient 'Corbella' olive variety from the center-north of Catalonia is being recovered to obtain quality extra-virgin olive oil (EVOO) with unique organoleptic properties. The aim of this work was to determine the effect of agronomic and technical factors on the phenolic fingerprint of EVOO and to establish the optimum harvesting time and crushing and malaxation conditions for 'Corbella' olives. Therefore, three different ripening indices (0.3, 1.2, and 3.2) and three crushing temperatures (10, 18, and 25 OC) were studied. Additionally, a factorial design to optimize the phenolic concentration of the EVOO was developed, applying a range of sieve diameters (4 and 6 mm), and malaxation time (30 and 60 min) and temperature (27, 32, and 37 °C). The phenolic profile was analyzed by ultra-high performance liquid chromatography coupled to mass spectrometry in a tandem detector. The level of secoiridoids, the major phenolic compounds in the oil, was higher when using olives harvested earlier. Oleuropein aglycone and ligstroside aglycone were degraded during crushing at high temperatures, resulting in the formation of oleacein and oleocanthal. The best processing conditions in terms of total phenolic content were found to be 30 min of malaxation at 37 OC, the crushing size not having any affect. [ABSTRACT FROM AUTHOR]

Oleocanthal (OLE), a characteristic and exclusive secoiridoid of Oleoaceae family, is mainly found in extra virgin olive oil (EVOO). Previous studies have reported its antioxidant, anti-inflammatory, antimicrobial, anticancer and neuroprotective effects. Since the pathogenesis of rheumatoid arthritis (RA) involves inflammatory and oxidative components, this study was designed to evaluate the preventive role of dietary OLE-supplemented effects in collagen-induced arthritis (CIA) murine model. Animals were fed with a preventive OLE-enriched dietary during 6 weeks previous to CIA induction and until the end of experiment time. At day 43 after first immunization, mice were sacrificed: blood was recollected and paws were histological and biochemically processed. Dietary OLE prevented bone, joint and cartilage rheumatic affections induced by collagen. Levels of circulatory matrix metalloproteinase (MMP)-3 and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-17, IFN-γ) were significantly decreased in secoiridoid fed animals. Besides, dietary OLE was able to diminish COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms underlying these protective effects could be related to Nrf-2/HO-1 axis activation and the inhibition of relevant signaling pathways including JAK-STAT, MAPKs and NF-κB, thus controlling the production of inflammatory and oxidative mediators. Overall, our results exhibit preliminary evidences about OLE, as a novel dietary tool for the prevention of autoimmune and inflammatory disorders, such as RA. [ABSTRACT FROM AUTHOR]

Extra virgin olive oil (EVOO), one of the key foods of the Mediterranean diet, is distinguished by its high content of nutritional and antioxidant compounds compared to other vegetable oils. During EVOO production, the major secoiridoids of EVOO, oleacein, oleocanthal, ligstroside, and oleuropein aglycones, undergo a series of transformations to open- and closed-structure forms. The resulting mixture of compounds can become more complex during the analytical procedure, due to the keto-enol tautomerism of the open forms and their interaction with polar solvents, and therefore more challenging to analyze. Employing the same extraction method used to analyze the other EVOO phenolic compounds, we report here a simple UHPLC-ESI-MS/MS procedure for the quantification of those secoiridoids that is able to co-elute the different isomers of each compound. The method was validated following AOAC guidelines, and the matrix effect and recoveries were within satisfactory limits. [ABSTRACT FROM AUTHOR]

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05–0.5 μmol/L; Ts: 0.001–0.1 μmol/L) and nutraceutical doses (Ps: 1–10 μmol/L; Ts: 0.25–10 μmol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 μmol/L; final nutraceutical concentration: 3 μmol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components. [ABSTRACT FROM AUTHOR]

In the last years, the interest in Italian monovarietal oils has increased due to their specific organoleptic qualities. Extra virgin olive oils (EVOOs) are rich in phenolic compounds, secondary metabolites well known and studied for their nutraceutical properties. However, among EVOOs, there is great variability in phenolic composition due to the origin, the production technique, and mainly, the genotype. The aim of this work was to evaluate the different phenolic profiles and the antioxidant activities of monovarietal oils. The results confirm this variability. In fact, the overall content of oleuropein varies up to four times between the different genotypes (from 33.80 to 152.32 mg/kg oil), while the oleocanthal content is significant only in two oils. The antioxidant activity, determined with 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays, is correlated with the content of total phenolic substances, with half maximal inhibitory concentration (IC50) values for the DPPH test ranging from 160 to 91 mg of oil, while the ORAC test shows values between 5.45 and 8.03 μmol Trolox equivalent (TE)/g oil. [ABSTRACT FROM AUTHOR]