Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

The olive-oil-centered Mediterranean diet has been associated with extended life expectancy and a reduction in the risk of age-related degenerative diseases. Extra virgin olive oil (EVOO) itself has been proposed to promote a “successful aging”, being able to virtually modulate all the features of the aging process, because of its great monounsaturated fatty acids content and its minor bioactive compounds, the polyphenols above all. Polyphenols are mostly antioxidant and anti-inflammatory compounds, able to modulate abnormal cellular signaling induced by pro-inflammatory stimuli and oxidative stress, as that related to NF-E2-related factor 2 (Nrf-2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which have been identified as important modulators of age-related disorders and aging itself. This review summarizes existing literature about the interaction between EVOO polyphenols and NF-κB and Nrf-2 signaling pathways. Reported studies show the ability of EVOO phenolics, mainly hydroxytyrosol and tyrosol, to activate Nrf-2 signaling, inducing a cellular defense response and to prevent NF-κB activation, thus suppressing the induction of a pro-inflammatory phenotype. Literature data, although not exhaustive, indicate as a whole that EVOO polyphenols may significantly help to modulate the aging process, so tightly connected to oxidative stress and chronic inflammation

Modulation of intestinal epithelium homeostasis by extra virgin olive oil phenolic compounds

Dietary habits have been strongly linked to the maintenance of intestinal epithelium homeostasis, whose alteration may contribute to the pathogenesis of inflammatory diseases and cancer. Polyphenols are among those dietary components suggested to be beneficial for gut health. Within a balanced Mediterranean type diet, a good portion of ingested polyphenols comes from olives and extra virgin olive oil (EVOO). Most of them reach the intestine, where they may be directly absorbed or metabolized under absorption. Others undergo an extensive gastrointestinal biotransformation, producing various metabolites that retain the potential beneficial effect of the parent compounds, or exert a more efficient biological action themselves. Ingested EVOO polyphenols (EVOOP) and their metabolites will be particularly concentrated in the intestinal lumen, where they might exert a significant local action. In this review we summarize the few studies that investigated the effect of EVOOP at the intestinal level, focusing on the possible mechanism of action in relation to their interaction with the microbiota, and their ability to potentially modulate the oxidative status of the intestinal epithelial layer, inflammation and immune response

Modulation of LPS-induced nitric oxide production in intestinal cells by hydroxytyrosol and tyrosol metabolites:Insight into the mechanism of action

At intestinal level, after acute or chronic exposure to iNOS-derived NO, a toxic mechanism of action leads to inflammation and degenerative diseases. The aim of this study was to investigate the effect of glucuronide and sulfate metabolites of the extra virgin olive oil phenols tyrosol (Tyr) and hydroxytyrosol (HT), in comparison with their parent compounds, on the release of NO following exposure to a pro-inflammatory stimulus, the bacterial lipopolysaccharide (LPS). Human colon adenocarcinoma cells (Caco-2), differentiated as normal enterocytes, were treated with pathological concentrations of LPS, in order to stimulate iNOS pathway, which involves NF-ĸB activation through IĸBα phosphorylation and subsequent degradation induced by Akt or MAPKs. All the tested metabolites inhibited NO release induced by LPS, acting as inhibitors of iNOS expression, with an efficacy comparable to that of the parent compounds. HT and Tyr metabolites were effective in the inhibition of IĸBα degradation. No one of the compounds was able to inhibit Akt activation, whereas they modulated p38 and ERK1/2 MAPK. Obtained data show that HT and Tyr metabolites are able to prevent a pathological NO overproduction at intestinal level, where they concentrate, thus significantly contributing to the protective activity exerted by their parent compounds against inflammation

Olive oil phenolics prevent oxysterol-induced proinflammatory cytokine secretion and reactive oxygen species production in human peripheral blood mononuclear cells, through modulation of p38 and JNK pathways

The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells. Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin-1β, regulated on activation, normal T-cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation. These results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes

Physical Exercise Modulates miR-21-5p, miR-129-5p, miR-378-5p, and miR-188-5p Expression in Progenitor Cells Promoting Osteogenesis

Physical exercise is known to promote beneficial effects on overall health, counteracting risks related to degenerative diseases. MicroRNAs (miRNAs), short non-coding RNAs affecting the expression of a cell's transcriptome, can be modulated by different stimuli. Yet, the molecular effects on osteogenic differentiation triggered by miRNAs upon physical exercise are not completely understood. In this study, we recruited 20 male amateur runners participating in a half marathon. Runners' sera, collected before (PRE RUN) and after (POST RUN) the run, were added to cultured human mesenchymal stromal cells. We then investigated their effects on the modulation of selected miRNAs and the consequential effects on osteogenic differentiation. Our results showed an increased expression of miRNAs promoting osteogenic differentiation (miR-21-5p, miR-129-5p, and miR-378-5p) and a reduced expression of miRNAs involved in the adipogenic differentiation of progenitor cells (miR-188-5p). In addition, we observed the downregulation of PTEN and SMAD7 expression along with increased AKT/pAKT and SMAD4 protein levels in MSCs treated with POST RUN sera. The consequent upregulation of RUNX2 expression was also proven, highlighting the molecular mechanisms by which miR-21-5p promotes osteogenic differentiation. In conclusion, our work proposes novel data, which demonstrate how miRNAs may regulate the osteogenic commitment of progenitor cells in response to physical exercise

Attività dello squalene durante l'autossidazione di acidi grassi poliinsaturi

In this paper we have investigated the activity of squalene during the autoxidation of four different polyunsaturated fatty acids: linoleic, linolenic, arachidonic and docosahexaenoic acids. Our results show that squalene exerts a weak but significant antioxidant activity, and that squalene hydroperoxide, the product derived from squalene oxidation, does not possess prooxidant activity. The protection exerted by squalene is higher versus linolenic, arachidonic and docosahexaenoic acids than linoleic acid. Squalene antioxidant activity is related to its double bond system since its saturated form, squalane, does not exert any inhibitory activity. Therefore, in our experimental conditions, squalene does not act as a hydrogen atoms donor such as α-tocopherol

Metabolic fingerprinting of chorionic villous samples in normal pregnancy and chromosomal disorders

Placenta-related biological samples are used in biomedical research to investigate placental development. Metabolomics represents a promising approach for studying placental metabolism in an effort to explain physiological and pathological mechanisms. The aim of this study was to investigate metabolic changes in chorionic villi during the first trimester of pregnancy in euploid and aneuploid cases

Terrestrial Laser Scanner and Close Range Photogrammetry point clouds accuracy assessment for the structure deformations monitoring

In this paper we show the results of several tests carried out using methods and instrumentation typical of an architectural survey, along with a set of metrological instrumentation, on a Reinforced Concrete (RC) beam subjected to increasing loads. The goal was to assess the accuracy in the displacements estimated by a medium quality terrestrial laser scanner (TLS) Focus 3d from Faro Technologies, and the low-cost digital camera Canon PowerShot S110 used in a Close Range Photogrammetry (CRP) survey. The software used for scan-data and point clouds processing was Reconstructor JRC Software v. 3.1.0, maintained by Gexcel Ltd, while the images processing was performed with the software Photoscan from Agisoft, which implements Structure from Motion (SfM) approach. Two processing strategies were used in the point clouds comparison: mesh2mesh and modelling the beam behavior fitting the contours of the beam with second order polynomials. Comparisons between the TLS and CRP techniques and the metrological equipment used in parallel highlighted the limits and potentialities of the two geomatic techniques used. It has been shown that modeling the behavior of the beam leads to significantly better results than using the mesh2mesh comparison. For the CRP the increase in accuracy was in the order of 40%, while for the TLS of 50%