Olive Oil Phenolic Compounds Research Articles

Cardiovascular and Metabolic Benefits of Extra Virgin Olive Oil Phenolic Compounds: Mechanistic Insights from In Vivo Studies.

Extra virgin olive oil (EVOO) represents a significant source of monounsaturated fatty acids (MUFA) and vitamin E, but it is also considered a functional food, due to the content of peculiar bioactive molecules, such as phenolic compounds, being able to modulate various processes related to aging and the most common metabolic and degenerative diseases. A lot of experimental research has focused on some of these components, but in most cases, the studies were performed in vitro testing compounds at non-physiological concentrations and achieving results that cannot easily be translated in vivo. Recent clinical studies demonstrated that in vivo these compounds are able to regulate physiological functions and prevent several pathological events including metabolic and cardiovascular diseases (CVDs), which represent the main causes of death worldwide. This review aims to sum up the major evidence on the beneficial effects of EVOO phenolic compounds in vivo on these pathologies, describing and evaluating the efficacy in relation to the mechanisms of diseases of the whole phenolic fraction and some of its specific components.

Anti-Cancer, Anti-Angiogenic, and Anti-Atherogenic Potential of Key Phenolic Compounds from Virgin Olive Oil.

The Mediterranean diet, renowned for its health benefits, especially in reducing cardiovascular risks and protecting against diseases like diabetes and cancer, emphasizes virgin olive oil as a key contributor to these advantages. Despite being a minor fraction, the phenolic compounds in olive oil significantly contribute to its bioactive effects. This review examines the bioactive properties of hydroxytyrosol and related molecules, including naturally occurring compounds (-)-oleocanthal and (-)-oleacein, as well as semisynthetic derivatives like hydroxytyrosyl esters and alkyl ethers. (-)-Oleocanthal and (-)-oleacein show promising anti-tumor and anti-inflammatory properties, which are particularly underexplored in the case of (-)-oleacein. Additionally, hydroxytyrosyl esters exhibit similar effectiveness to hydroxytyrosol, while certain alkyl ethers surpass their precursor's properties. Remarkably, the emerging research field of the effects of phenolic molecules related to virgin olive oil on cell autophagy presents significant opportunities for underscoring the anti-cancer and neuroprotective properties of these molecules. Furthermore, promising clinical data from studies on hydroxytyrosol, (-)-oleacein, and (-)-oleocanthal urge further investigation and support the initiation of clinical trials with semisynthetic hydroxytyrosol derivatives. This review provides valuable insights into the potential applications of olive oil-derived phenolics in preventing and managing diseases associated with cancer, angiogenesis, and atherosclerosis.

Extra Virgin Olive Oil Phenolic Compounds Modulate the Gene Expression of Biomarkers Involved in Fibroblast Proliferation and Differentiation.

Extra virgin olive oil phenolic compounds have been identified as possible biostimulant agents against different pathological processes, including alterations in healing processes. However, there is little evidence on the molecular mechanisms involved in this process. The aim was to analyse the effect of hydroxytyrosol, tyrosol, and oleocanthal on fibroblast gene expression. PCR was used to determine the expression of different differentiation markers, extracellular matrix elements, and growth factors in cultured human fibroblasts CCD-1064Sk treated with different doses of hydroxytyrosol (10-5 M and 10-6 M), tyrosol (10-5 M and 10-6 M), and oleocanthal (10-6 M and 10-7 M). After 24 h of hydroxytyrosol treatment, increased expression of connective tissue growth factor, fibroblast growth factor (FGF), platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor β1 (TGF-β1), and their receptors was observed. Tyrosol and olecanthal modulated the expression of FGF and TGFβR1. All phytochemicals tested modified the expression of differentiation markers and extracellular matrix elements, increasing gene expression of actin, fibronectin, decorin, collagen I, and III. Phenolic compounds present in extra virgin olive could have a beneficial effect on tissue regeneration by modulating fibroblast physiology.

Olive Oil's Attenuating Effects on Lipotoxicity.

Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.

A new insight into synergistic effects between endogenous phenolic compounds additive and α-tocopherol for the stability of olive oil.

Investigation of edible oil stability involves interactions between additive polyphenols and the inherent tocopherols. The work aimed to identify endogenous polyphenols to produce the synergistic effect with α-tocopherol in olive oil and to find the right action ratio. Caffeic acid and quercetin were selected from the 15 main endogenous phenolic compounds in olive oil. Quercetin had the strongest synergistic effect with α-tocopherol at 2:1 in the olive oil model. The rate of 2:1 also was the turning point of the change of synergism. Furthermore, the addition of quercetin and α-tocopherol at 2:1 to olive oil resulted in lower POV, K232, K270, and secondary oxidation products such as (E, E)-2,4-decadienal and 2-pentylfuran than the olive oil model with a single antioxidant in three months of accelerated oxidation. The dynamic changes of antioxidants during oxidation in olive oil indicated that their synergistic effect was the repair and regeneration of α-tocopherol by quercetin.

Olive Oil Phenolic Compounds' Activity against Age-Associated Cognitive Decline: Clinical and Experimental Evidence.

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicate that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption of olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications.

Rich oleocanthal and oleacein extra virgin olive oil and inflammatory and antioxidant status in people with obesity and prediabetes. The APRIL study: A randomised, controlled crossover study

Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human studies have examined the health benefits of olive oils rich in these biophenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity. Randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40kg/m2) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No changes in diet or physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, glucose handling and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis. A total of 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P=0.041). Total antioxidant status increased and lipid and organic peroxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P<0.05). Decreases in weight, BMI and blood glucose (p<0.05) were found after treatment with EVOO and not with OO. Treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes.

Co-Extraction Technique Improves Functional Capacity and Health-Related Benefits of Olive Oils: A Mini Review.

Olive oil, a fundamental component of the Mediterranean diet, is recognized as a functional food due to its health-promoting composition. The concentration of phenolic compounds in olive oil is influenced by various factors such as genetics, agro-climatic conditions, and technological processes. Therefore, to ensure an ideal intake of phenolics through the diet, it is recommended to produce functional enriched olive oil that contains a high concentration of bioactive compounds. The co-extraction technique is used to create innovative and differentiated products that promote the sensory and health-related composition of oils. To enrich olive oil, various natural sources of bioactive compounds can be used, including raw materials derived from the same olive tree such as olive leaves, as well as other compounds from plants and vegetables, such as herbs and spices (garlic, lemon, hot pepper, rosemary, thyme, and oregano). The development of functional enriched olive oils can contribute to the prevention of chronic diseases and improve consumers' quality of life. This mini-review compiles and discusses relevant scientific information related to the development of enriched olive oil using the co-extraction technique and its positive effects on the health-related composition of oils.

Effect of olive oil phenols on oxidative stress biomarkers: A systematic review and dose-response meta-analysis of randomized clinical trials.

The phenolic content of olive oil has a role in cardiovascular protection. Some clinical trial studies demonstrated that phenolic compounds of olive oil have antioxidant activity which can protect macronutrients from oxidative damages. The aim of this study was to summarize the results of clinical trials which assessed the effects of high- versus low-phenol olive oil on oxidative stress biomarkers levels. We searched Scopus, PubMed, Web of Science, Google Scholar, ProQuest, and Embase up to July 2021. Eight clinical trials which evaluated the effect of the phenolic content of olive oil on oxidized-LDL (ox-LDL), malondialdehyde (MDA), or ferric-reducing ability of plasma (FRAP) were included the meta analysis. A significant decrease was observed in ox-LDL level (WMD: -0.29 U/L; 95% CI: -0.51, -0.07) and MDA (WMD: -1.82 μmoL/L; 95% CI: -3.13, -0.50). However, after subgroup analysis for MDA, the result was not significant for not serious limitation (SMD: -0.05, 95% CI: -0.35 to 0.24), but significant for serious limitation (SMD: -3.64, 95% CI: -4.29 to -2.99). Also, no significant change was found in FRAP (WMD: 0.0 mmoL/L; 95% CI: -0.03, 0.04) level. Dose-response analysis indicated a significant linear relationship between the phenolic content of olive oil and ox-LDL. The present study showed some beneficial effects of high-phenol compared with low-phenol olive oil on ox-LDL and MDA levels. According to the meta-regression analysis along with the increasing phenolic content of olive oil, a reduction in oxidative stress biomarkers was observed.

Maximising olive oil by‐products

Maximising olive oil by‐products

Application of Doehlert Experimental Design for Optimization of a New-Based Hydrophilic Interaction Solid-Phase Extraction of Phenolic Acids from Olive Oils.

In this work, a rapid, precise, and cost-valuable method has been established to quantify phenolic compounds in olive oil using new-based hydrophilic interaction solid-phase extraction (SPE). Boehlert's experimental design applied the determination of the optimal operating conditions. An investigation into the effects of the methanol composition (50-100%), the volume of eluent (1-12 mL), and pH (1-3) on the extraction of phenols acids and total phenols from Tunisian olive oils was performed. The results showed that the extraction conditions had a significant effect on the extraction efficiency. The experiment showed that the greatest conditions for the SPE of phenolic acids were the methanol composition at 90.3%, pH at 2.9, and volume at 7.5 mL, respectively. The optimal conditions were applied to different types of olive oils, and it could be concluded that larger concentrations of polyphenols were found in extra virgin olive oil (89.15-218), whereas the lowest levels of these compounds (66.8 and 5.1) were found in cold-pressed crude olive oil and olive pomace oil, respectively.

Extraction and Quantification of Bioactive Phenolic Compounds in Olive Oil by Acid Hydrolysis Method

Extraction and Quantification of Bioactive Phenolic Compounds in Olive Oil by Acid Hydrolysis Method

Physico-chemical properties, tocopherol contents, fatty acid composition and phenolic compounds of olive oil as affected by papain and cellulase application

Physico-chemical properties, tocopherol contents, fatty acid composition and phenolic compounds of olive oil as affected by papain and cellulase application

Impact of Phenol-Enriched Olive Oils on Serum Metabonome and Its Relationship with Cardiometabolic Parameters: A Randomized, Double-Blind, Cross-Over, Controlled Trial.

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum 1H-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases.

Antibacterial Activity of Phenolic Compounds in Olive Oil Extracts on Periodontopathogenic Oral Bacteria

Phenolic compounds are secondary metabolites of plants metabolism and can be found in olive oil. They exhibit antimicrobial activity towards both gram-positive and gram-negative bacteria. However, little is known about the antibacterial activity of the compounds towards periodontopathogens. The study aimed to investigate the potential of these compounds as antibacterial agents towards pathogens, specifically Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum. Phenolic compounds were extracted from extra virgin olive oil (EVOO) through liquid-liquid separation using methanol:water (70:30), and hexane. It was then prepared in various concentrations to determine its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against the periodontopathogens. The anti-adhesion activity was quantified using crystal violet staining while the effects on the morphology were examined through scanning electron microscopy (SEM). The MICs of the phenolic compounds on A. actinomycetemcomitans, P. gingivalis and F. nucleatum were 31.25 mg/mL, 62.5 mg/mL and 125 mg/mL, respectively. The MBCs of the phenolic compounds on A. actinomycetemcomitans and F. nucleatum were 62.5 mg/mL and 125 mg/mL, respectively suggesting this compound can eradicate these bacteria. There was no bactericidal effect on P. gingivalis. The adhesion of all the bacteria was interrupted by the compounds at the lowest concentration (1.95 mg/mL). SEM findings showed disruption of bacterial cell surfaces such as blebs and disintegration of cells after exposure to this extract. Phenolic compounds of olive oil exhibited antibacterial activity against the tested pathogens, with bactericidal effects on A. actinomycetemcomitans and F. nucleatum and bacteriostatic effects on P. gingivalis.

Chemical composition of olive oil – an essential component of the Mediterranean diet and its impact on human health

The Mediterranean diet is known for its many health benefits, including the low prevalence of cardiovascular disease, atherosclerosis, diabetes, obesity, and cancer. Olive oil is considered an essential component of the Mediterranean diet. The consumption of olive oil is associated with many beneficial effects on the human body, most of which are attributed to its phenol content, which varies between cultivars due to different processing and extraction procedures, with only 0.3-1.5% of phenols being transferred to the oil from the olive fruit. Many studies suggest that olive oil phenolic compounds have a protective role in preventing cardiovascular diseases, cancer, diabetes mellitus type 2, metabolic syndrome, obesity, inflammation, and neurodegenerative diseases. Additionally, recent epidemiological research has shown that regular olive oil consumption is associated with increased longevity. Keywords: olive oil, phenols, health benefits

Hydroxytyrosol Prevents Doxorubicin-Induced Oxidative Stress and Apoptosis in Cardiomyocytes.

Doxorubicin (Dox) is a highly effective chemotherapeutic agent employed in the handling of hematological and solid tumors. The effective use of Dox in cancer therapy has been seriously limited due to its well-known cardiotoxic side effects, mainly mediated by oxidative damage. Therefore, the identification of an effective and safe antagonist against Dox-induced cardiotoxicity remains a challenge. In this respect, as plant polyphenols have attracted considerable interest due to their antioxidant properties and good safety profile, hydroxytyrosol (HT), the major phenolic compound in olive oil, could be a potential candidate due to its remarkable antioxidant and anticancer powers. In this study, the effect of HT was tested on Dox-induced cardiotoxicity by using a combination of biochemical and cellular biology techniques. Interestingly, HT was able to counteract Dox-induced cytotoxicity in cardiomyocytes by acting on the SOD2 level and the oxidative response, as well as on apoptotic mechanisms mediated by Bcl-2/Bax. At the same time, HT did not to interfere with the antitumorigenic properties of Dox in osteosarcoma cells. This study identifies new, beneficial properties for HT and suggests that it might be a promising molecule for the development of additional therapeutic approaches aimed at preventing anthracycline-related cardiotoxicity and improving long-term outcomes in antineoplastic treatments.

Nutrition during pregnancy and lactation: New evidence for the vertical transmission of extra virgin olive oil phenolic compounds in rats

Maternal breast milk provides the newborn with passive immunity and stimulates the maturation of the infant immune system. The aim of the present study was to evaluate the vertical transmission of phenolic compounds and their metabolites to offspring in rats fed with extra virgin olive oil (EVOO) during pregnancy and lactation. For this purpose, plasma and lactic serum from dams and plasma from offspring were analyzed by LC-ESI-LTQ-Orbitrap-MS. Both enzymatic and microbial metabolites of hydroxytyrosol and tyrosol were detected in dam plasma and lactic serum. In addition, significant levels of phenolic compounds and their metabolites were found in offspring plasma. The concentration and number of hydroxytyrosol derivatives was higher than those of tyrosol and the microbial metabolites were found in the highest concentration. The observed vertical transmission of EVOO phenolic compounds, whose health benefits are widely reported, provides further support for the importance of the maternal diet during pregnancy and lactation.

Abstract 316: Hydroxytyrosol, An Olive Oil Phenol, Reduces Ex Vivo Thrombin-induced Platelet Activation

Background and Aims: Olive oil consumption is associated with lower cardiovascular disease (CVD) risk. We recently demonstrated that frequent olive oil consumption was inversely associated with thrombin-induced platelet activation ex vivo . While various olive oil phenolic compounds, notably hydroxytyrosol, have been shown to reduce human platelet aggregation ex vivo , little is known about how olive oil affects platelet activation, a key mediator of atherothrombosis. Therefore, we sought to investigate whether hydroxytyrosol exposure affects platelet activation. Methods and Results: Ten healthy, non-smoking men and women (25.0±1.6 years) with normal body mass index (BMI 22.2±3.3 kg/m 2 ) were recruited for ex vivo platelet studies. Individuals on antiplatelet or anticoagulation medications or medications known to influence lipid levels were excluded. Subjects attended a single visit at NYU Langone where platelet-rich plasma (PRP) was isolated and incubated with three different concentrations of hydroxytyrosol or ethanol vehicle for 60 minutes at room temperature. PRP was then incubated with bovine thrombin for 5 minutes followed by anti-CD62P for 15 minutes in the dark. Platelet activation was determined by platelet surface expression of P-selectin, assessed via flow cytometry. E x vivo exposure to hydroxytyrosol inhibited thrombin-induced platelet P-selectin expression in a dose-dependent manner (Figure). Conclusions: We demonstrate that hydroxytyrosol exposure reduces thrombin-induced platelet P-selectin expression in a dose-response fashion. The dose response seen in this ex vivo platelet activation study is consistent with our clinical observation that more frequent olive oil intake was associated with reduced ex vivo thrombin-induced P-selectin expression. This laboratory study suggests a putative mechanism underlying our clinical observation as well as the established inverse association of olive oil consumption with CVD.

Comparative study of phenolic compounds in olive oils from differentgeographic regions

In this study, the effect of cultivar, harvest year, and the geographic regions (Mediterranean, Aegean, Southeastern Anatolia, Marmara, and the Black Sea) on phenolic compounds of virgin olive oils were investigated. Tyrosol was the major phenolic compound in the Mediterranean, Southeastern, and Black Sea regions. Hydroxytyrosol showed the highest value (2.07 mg/kg) in the Southeastern Anatolia region and the lowest value (0.75 mg/kg) in the Marmara region. Among the phenolic acids, vanillic acid had an important place in phenolic compounds (p < 0.01). This phenolic acid gave higher values in the Marmara region compared to other regions. Flavonoids were determined as important groups of phenolic compounds in olive oils. The oils from the Southeastern Anatolia region separated from other oils with the highest levels of flavonoids such as quercetin, luteolin, and apigenin. All phenolic compounds, except transcinnamic acid and quercetin, increased in the second harvest year. Vanillic acid was the highest phenolic compound in the first year, in contrast, tyrosol had higher values than vanillic acid in the second year. Many phenolic compounds were affected by olive cultivar. Memecik has a higher content of tyrosol, vanillic acid, p-coumaric acid, ferulic acid, and quercetin in the Aegean region. However, this variety showed higher values for hydroxytyrosol, transcinnamic acid, luteolin, and apigenin in the Marmara region. Gemlik, Ayvalık, Çelebi, Domat and Memecik from Marmara regions had higher vanillic acid. Butko, Otur and Kızıl Satı showed higher tyrosol. Principal component analysis showed that phenolic compounds could play an important role in the separation of regions and cultivars.