Endocrine, Metabolic & Immune Disorders-Drug Targets - Volume 18, Issue 1, 2018

Background and Objective: The cardioprotective properties of Mediterranean Diet were demonstrated for the first time from the Seven Country Study. In the last few decades, numerous epidemiological studies, as well as intervention trial, confirmed this observation, pointing out the close relationship between the Mediterranean diet and cardiovascular diseases. In this context, extra virgin olive oil (EVOO), the most representative component of this diet, seems to be relevant in lowering the incidence of cardiovascular events, including myocardial infarction and stroke. From a chemical point of view, 98-99% of the total weight of EVOO is represented by fatty acids, especially monounsaturated fatty acids such as oleic acid. Tocopherols, polyphenols and other minor constituents represent the remaining 1-2%. All these components may potentially contribute to ”health maintenance” with their beneficial effects by EVOOO. Methods: Studies that examined the effect of EVOO supplementation in healthy subjects and in individuals at cardiovascular risk were included. Conclusion: The studies analyzed demonstrated the role of EVOO as anti-inflammatory, antioxidant and vasodilatory nutrient that may contribute to lower the atherosclerotic burden.

Background and Objective: Extra virgin olive oil (EVOO) is the common element among the Mediterranean countries. It can be considered a nutraceutical and functional food, thanks to its bioactive compounds. It can act and modulate different processes linked to ageing and age-related diseases related to a common chronic low grade inflammation. Depending on the cultivar, the growth conditions, the period of harvesting, the productive process and time of product storage, EVOO could contain different amount of vegetal components. Of course, the same is for table olives. Methods: The aim of our review is to summarize the effects of EVOO and table olives on the immunemediated inflammatory response, focusing our attention on human studies. Results: Our report highlights the effect of specific molecules obtained from EVOO on the modulation of specific cytokines and anti-oxidants suggesting the importance of the daily consumption of both EVOO and table olives in the context of a Mediterranean dietary pattern. In addition, the different action on immune-inflammatory biomarkers, are depending on the olive tree cultivar. Conclusion: Thanks to their bioactive compounds, EVOO and table olive can be considered as nutraceutical and functional foods. The beneficial effects analysed in this review will help to understand the potential application of specific olive components as therapeutic adjuvant, supplements or drugs.

Background and Objective: The increasing interest in the Mediterranean diet (MeDiet) hinges on the relevant role it plays in inflammatory diseases. Several clinical, epidemiological and experimental evidences suggest that consumption of the MeDiet reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation and immune system diseases such as cancer, atherosclerosis and cardiovascular disease (CVD). These reductions can be partially attributed to extra virgin olive oil (EVOO) consumption which has been described as a key bioactive food because of its high nutritional quality and its particular composition of fatty acids, vitamins and polyphenols. Indeed, the beneficial effects of EVOO have been linked to its fatty acid composition, which is very rich in monounsaturated fatty acids (MUFA), and has moderate saturated and polyunsaturated fatty acids (PUFA). The current knowledge available on the beneficial effects of EVOO and its phenolic compounds, specifically its biological properties and antioxidant capacity against immune-mediated inflammatory responses (atherosclerosis, rheumatoid arthritis, diabetes, obesity, cancer, inflammatory bowel disease or neurodegenerative disease, among others) in addition to its potential clinical applications. Conclusion: The increasing body of studies carried out provides compelling evidence that olive polyphenols are potential candidates to combat chronic inflammatory states.

Background and Objective: Altered inflammatory response characterizes chronic immunemediated inflammatory diseases (IMID) such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis. Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with a reduced risk of developing chronic degenerative disorders such as cardiovascular diseases, type 2 diabetes and cancer. The beneficial effects on health of EVOO have been attributed, besides to the monounsaturated fats content, to the presence of phenolic compounds that have antioxidant, anti-inflammatory and immunomodulatory properties. The purpose of this review is to provide an overview of the effects of EVOO polyphenols on IMID highlighting the potential mechanisms of action. Methods: Scientific papers were found by searching in PubMed up to May 2017 using the following key words: rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis also in combination with EVOO, phenolic compounds, oleuropein, oleocantal, hydroxytyrosol,tyrosol and oleochantal. Results: In vitro and in vivo studies indicate that EVOO and its polyphenols can improve diseases symptoms in IMID, by acting both at local and systemic levels and by modulating several molecular pathways. Nevertheless, there are not sufficient data to achieve specific nutritional guidelines. Conclusion: Further research is needed to evaluate the real contribution of EVOO and its phenolic compounds in modulating the IMID-associated inflammatory perturbations, in order to develop appropriate nutritional recommendations.

Background and Objective: Atherosclerosis is characterized by a chronic low-grade inflammatory process which can result in atherothrombosis and a number of cardiovascular diseases (CVD). It is believed to be caused by multiple processes that involve inflammation and immunity. Mediterranean Diet (MedD) has been discovered to possess anti-inflammatory properties and associated with a reduction in the CVD risk and mortality. Its main component, extra-virgin olive oil (EVOO), is believed to be largely responsible for these effects and therefore, has been investigated in various studies. The present review article aims to summarize the available literature on the antiinflammatory and cardio-protective effects of EVOO. Methods: A search based on the key concepts “olive oil”, “atherosclerosis”, “inflammation” and “cardiovascular disease” was performed to retrieve relevant studies and articles on the association between the consumption of EVOO and the levels of inflammatory biomarkers as well as CVD incidence and mortality from online databases; Pubmed, Embase and Cochrane Library. Results: Consumption of EVOO is associated with a reduction in inflammatory biomarkers and molecules implicated in atherosclerosis as well as CVD incidence and mortality as well as other complications such as heart failure and atrial fibrillation. Moreover, these anti-inflammatory and cardioprotective effects of EVOO are mostly attributable to its high content of polyphenol molecules. Conclusion: Currently available evidence supports the anti-inflammatory and cardio-protective roles of EVOO. However, there is limited amount of available randomized controlled trials especially lacking those investigating the use of EVOO as secondary prevention, heterogeneity of study design, limited generalization to wide population groups, and inability to determine the minimum intake of EVOO required to clinically achieve the anti-inflammatory and cardioprotective effects. Therefore, more highquality randomized controlled trials still need to be carried out to overcome these challenges to further assess the health benefits of EVOO consumption and potentially translate it into clinical practice as primary or secondary prevention of atherosclerosis-related conditions.

Background and Objective: Tumor necrosis factor-alpha (TNF)-α and interleukin (IL)-6 are important mediators of chronic low-grade systemic inflammation. The latter plays a central role in several obesity-related pathologies, such as diabetes, metabolic syndrome and cardiovascular diseases. Besides, these cytokines have been also implicated in geriatric and cancer-induced anorexia, cachexia, sarcopenia and frailty. Potential interventions for both obesity and frailty include dietary advice and nutraceuticals. In this context, the consumption of olive oil (OO) has been associated with the health effects of the Mediterranean diet (Med-diet). This review is aimed to discuss the OO-mediated modulation of TNF- α and IL-6 in human studies and the potential implication in obesity and frailty. Results: The reviewed studies suggest that the improvement of postprandial TNF-α and IL-6 observed with OO consumption is affected by body mass index (BMI). The effects on TNF-α and IL-6 after medium and long-term consumptions involved many factors and the cross-talk between adipose tissue, liver, skeletal muscle and brain. Major anti-inflammatory effects were observed when OO was consumed with Med-diet, which is associated with healthy behaviors. In this context, the role of microbioma- polyphenols, diet-gene and exercise-gene interactions in the effects of OO on immune-mediated inflammatory responses involved in obesity and frailty deserves further investigation. Conclusion: Further studies are needed to clarify the effect of OO net of possible synergistic effects with other dietary and lifestyle factors of Mediterranean area.

Background and Objective: The liver is an organ susceptible to a multitude of injuries that causes liver damage, like steatosis, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Extra virgin olive oil (EVOO), presents several protective effects on the liver, reducing hepatic steatosis, hepatocyte ballooning, fibrogenesis, preventing lipid peroxidation, among other effects. Due to its high levels of monounsaturated fatty acids, mainly oleic acid and phenolic compounds, such as hydroxytyrosol and oleuropein, EVOO is able to participate in the activation of different signaling pathways in the hepatocytes involved in the prevention of inflammation, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and insulin resistance, allowing the prevention or resolution of liver damage. The aim of this work is to offer an update of the molecular effects of EVOO in the liver and its protective properties to prevent the establishment of liver damage through the regulation of different cell-signaling pathways. Methods: Searches that considered the effects of EVOO in in vivo and in vitro models, whith emphasis in the molecular mechanism of liver tissue damage and prevention and/or treatment of steatosis, steatohepatitis, cirrhosis, hepatocellular carcinoma, and ischemia-reperfusion injury. Conclusion: The most relevant molecular effects of EVOO involved in the prevention or resolution of liver damage are: (i) Activation of the nuclear transcription factor erythroid-derived 2-like 2 (Nfr2), inducing the cellular antioxidant response; (ii) Inactivation of the nuclear transcription factor-ΚB (NF- ΚB), preventing the cellular inflammatory response; and (iii) Inhibition of the PERK pathway, preventing endoplasmic reticulum stress, autophagy, and lipogenic response.

Background: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs. Methods: Peripheral blood mononuclear cells from twenty-five healthy donors were cultured in the presence of 3 μg of two OLE extracts, extract A (resuspended in water) and extract B (resuspended in 70% ethanol). After harvesting, cell pellets were used for cytofluorimetric phenotyping, while supernatants were assayed for cytokine release by means of ELISA. Furthermore, in the same supernatants nitric oxide (NO) content was determined. Results: Both extracts, but especially extract A, increased absolute numbers of CD8+ and natural killer (NK) cells. In addition, an increased production of interferon (IFN)-γ by both extracts as an expression of T helper (h)1 activation was observed. Finally, both extracts enhanced NO release. Conclusion: OLEs, and mostly extract A, are able to in vitro modify healthy human immune response by increasing IFN-γ production which seems to be associated to the higher absolute numbers of CD8+ and NK cells and this may suggest a reinforcement of the anti-tumor activity. Furthermore, increased levels of NO may indicate the potential cardioprotective effects exerted by OLEs in virtue of their vasodilation dependent activity. Finally, OLEs are able to maintain the equilibrium between T regulatory cells and Th17 cells as evidenced by unmodified levels of interleukin (IL)-IL-10 and IL-17, respectively. In the light of these results, OLEs are potential therapeutic compounds for the treatment of chronic inflammatory disease, also preventing cardiovascular event outcome.