Olive Phenols Research Articles

Phytochemical Compounds as Promising Therapeutics for Intestinal Fibrosis in Inflammatory Bowel Disease: A Critical Review

Background/Objective: Intestinal fibrosis, a prominent consequence of inflammatory bowel disease (IBD), presents considerable difficulty owing to the absence of licensed antifibrotic therapies. This review assesses the therapeutic potential of phytochemicals as alternate methods for controlling intestinal fibrosis. Phytochemicals, bioactive molecules originating from plants, exhibit potential antifibrotic, anti-inflammatory, and antioxidant activities, targeting pathways associated with inflammation and fibrosis. Compounds such as Asperuloside, Berberine, and olive phenols have demonstrated potential in preclinical models by regulating critical signaling pathways, including TGF-β/Smad and NFκB, which are integral to advancing fibrosis. Results: The main findings suggest that these phytochemicals significantly reduce fibrotic markers, collagen deposition, and inflammation in various experimental models of IBD. These phytochemicals may function as supplementary medicines to standard treatments, perhaps enhancing patient outcomes while mitigating the adverse effects of prolonged immunosuppressive usage. Nonetheless, additional clinical trials are necessary to validate their safety, effectiveness, and bioavailability in human subjects. Conclusions: Therefore, investigating phytochemicals may lead to crucial advances in the formulation of innovative treatment approaches for fibrosis associated with IBD, offering a promising avenue for future therapeutic development.

Nutraceutical Supplementation as a Potential Non-Drug Treatment for Fibromyalgia: Effects on Lipid Profile, Oxidative Status, and Quality of Life.

Fibromyalgia (FM) is a chronic syndrome of unknown etiology, although many studies point to inflammation, oxidative stress, and altered mitochondrial metabolism as some of the cornerstones of this disease. Despite its socioeconomic importance and due to the difficulties in diagnosis, there are no effective treatments. However, the use of non-drug treatments is increasingly becoming a recommended strategy. In this context, the effects of supplementation of FM patients with an olive (poly)phenol, vitamin C, and vitamin B preparation were investigated in this work, analyzing complete blood count, biochemical, lipid, and coagulation profiles, and inflammation and oxidation status in blood samples. To gain a better understanding of the molecular mechanisms and pathways involved in the etiology of FM, a proteomic study was also performed to investigate the mechanisms of action of the supplement. Our results show that the nutraceutical lowers the lipid profile, namely cholesterol, and improves the oxidative status of patients as well as their quality of life, suggesting that this product could be beneficial in the co-treatment of FM. ClinicalTrials.gov (ID: NCT06348537).

Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Caenorhabditis elegans Longevity and Stress Resistance.

Oleacein, a bioactive compound of olive oil and olive mill wastewater, has one of the strongest antioxidant activities among olive phenolics. However, few reports explore the in vivo antioxidant activity of oleacein, with no clear identification of the biological pathway involved. Earlier studies have demonstrated a link between stress resistance, such as oxidative stress, and longevity. This study presents the effects of oleacein on Caenorhabditis elegans mean lifespan and stress resistance. A significant lifespan extension was observed with an increase of 20% mean lifespan at 5 µg/mL with a hormetic-like dose-dependent effect. DAF-16 and SIR-2.1 were involved in the effects of oleacein on the longevity of C. elegans, while the DAF-2 receptor was not involved. This study also shows the capacity of oleacein to significantly enhance C. elegans resistance to oxidative and thermal stress and allows a better understanding of the positive effects of olive phenolics on health.

Identification and Evaluation of Olive Phenolics in the Context of Amine Oxidase Enzyme Inhibition and Depression: In Silico Modelling and In Vitro Validation.

The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea, and of these, only a relatively small fraction have been characterised. Utilising the OliveNetTM library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1). Furthermore, the compounds were screened for inhibition of the structurally similar monoamine oxidases (MAOs) which are directly implicated in the pathophysiology of depression. Molecular docking highlighted that olive phenolics interact with the active site of LSD1 and MAOs. Protein-peptide docking was also performed to evaluate the interaction of the histone H3 peptide with LSD1, in the presence of ligands bound to the substrate-binding cavity. To validate the in silico studies, the inhibitory activity of phenolic compounds was compared to the clinically approved inhibitor tranylcypromine. Our findings indicate that olive phenolics inhibit LSD1 and the MAOs in vitro. Using a cell culture model system with corticosteroid-stimulated human BJ fibroblast cells, the results demonstrate the attenuation of dexamethasone- and hydrocortisone-induced MAO activity by phenolic compounds. The findings were further corroborated using human embryonic stem cell (hESC)-derived neurons stimulated with all-trans retinoic acid. Overall, the results indicate the inhibition of flavin adenine dinucleotide (FAD)-dependent amine oxidases by olive phenolics. More generally, our findings further support at least a partial mechanism accounting for the antidepressant effects associated with EVOO and the Mediterranean diet.

Functional food development using olive pomace phenolics and hydrogels

SummaryAlthough the health effects of olive phenolics, hydroxytyrosol (HX), are well known, their utilisation is not at the forefront of the phenolics market. Besides, 99% of olive phenolics are lost during olive oil production (2.2 million tons year−1). This study aims to develop a functional hydrogel for functional foods using commercial olive powder derived from olive mill wastewater and methylcellulose (MC). The final hydrogel recipe, a multi‐hydrocolloid recipe (MC and gelatine with low gelling temperature) based on minimum HX loss and acceptable sensory properties, was created by examining interactions of HX with salt, sugar, and citric acid in MC by a modified UPLC‐UV method and expert sensory panellists. Finally, two dairy bases were created for the hydrogel with the best aroma match, and consumer‐accepted dessert (72%) and appetiser (58%) providing the health claims of European Food Safety Authority (EFSA) (2 mg day−1 of HX) were produced. Moreover, a sample methodology has been developed.

Influences of lactic acid bacterial fermentation on the physicochemical properties and biological activities of olive phenols

SummaryOlives are a popular fruit in China, often consumed as olive juice beverages due to their richness in phenolic compounds. Fermentation by lactic acid bacteria has been shown to enhance the nutritional and health benefits of fruits and vegetables. However, the effect of fermentation on olive phenolics during in vitro‐simulated digestion has not yet been reported. This study aimed to explore changes in total polyphenol content, antioxidant capacity, xanthine oxidase inhibition, and effects on simulated digestion of olive phenolics before and after fermentation of olive fruits. Fermentation increased the total phenolic content, antioxidant capacity and XO inhibition activity of olive phenolics and these differences were maintained after simulated gastrointestinal digestion. This means that fermented olives should have greater biological activity in general as well as greater human health benefits. Phenolic extracts of fermented olives contained six phenolics with a higher content than unfermented olives after simulated gastrointestinal digestion. These findings help to improve understanding of the benefits of fermentation for producing health‐beneficial functional foods from fruits and vegetables that are rich in phenolic compounds.

Fermentation of olive pulp by Limosilactobacillus fermentumNCU001464: physicochemical properties, biological activity and bioactive phenols

SummaryOlives, which are rich in bioactive compounds, are processed into beverages in China. We investigated the effect of fermentation by Limosilactobacillus fermentum NCU001464 on the physicochemical characteristics, biological activities and phenolic compounds of olive pulp. After fermentation for 48 h, pH and individual sugar content of olive pulp decreased. Lm. fermentum NCU001464 fermentation enhanced the hydroxyl radical scavenging activity and the inhibitory effect against xanthine oxidase (XO) of olive pulp. Total phenol content was not significantly different between olive pulp fermented for 0 and 48 h. However, the fermented olive phenol extract had a lower IC50 value than the unfermented phenol extract. Fluorescence spectroscopy results revealed that the olive phenol extract had a stronger XO inhibitory effect after fermentation. The dominant binding forces between olive phenols and XO were hydrogen bonds and van der Waals forces. There were 31 different phenolic compounds between the unfermented and fermented extracts.

Efficacy of Hydroxytyrosol-Rich Food Supplements on Reducing Lipid Oxidation in Humans.

In the present study we report the efficacy of two food supplements derived from olives in reducing lipid oxidation. To this end, 12 healthy volunteers received a single dose (25 mL) of olive phenolics, mainly hydroxytyrosol (HT), provided as a liquid dietary supplement (30.6 or 61.5 mg HT), followed by an investigation of two reliable markers of oxidative stress. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h post-intake. Plasma-oxidized low-density lipoprotein (oxLDL) cholesterol levels were measured with ELISA using a monoclonal antibody, while F2-isoprostanes (F2-IsoPs) were quantified in urine with UHPLC-DAD-MS/MS. Despite the great variability observed between individuals, a tendency to reduce lipoxidation reactions was observed in the blood in response to a single intake of the food supplements. In addition, the subgroup of individuals with the highest baseline oxLDL level showed a significant (p < 0.05) decrease in F2-IsoPs at 0.5 and 12 h post-intervention. These promising results suggest that HT supplementation could be a useful aid in preventing lipoxidation. Additionally, people with a redox imbalance could benefit even more from supplementing with bioavailable HT.

Maximising olive oil by‐products

Maximising olive oil by‐products

Microencapsulation of olive mill wastewater in Saccharomyces cerevisiae cells by spray drying and in vitro bioaccessibility of phenolic compounds.

Olive-mill wastewater (OMW), a by-product with high biological value and rich in phenolic compounds, is converted into spray-dried powders by using baker's yeast cells (YCs) as the carrier material. The encapsulation of OMW into YCs was also confirmed by Fourier transform infrared spectroscopy (FT-IR) analysis. The encapsulation yield (%) of powders for OMW phenolics was determined as 5.42 ± 0.33 and 4.02 ± 0.01% in YC microparticles non-treated and treated with high-pressure homogenization (HPH), respectively. The distorted structure of YCs, observed in scanning electron microscopy images, reduced the retention of OMW phenolics by YCs. HPH application made water removal easier, and the moisture content of YC-OMW powders was reduced from 5.13 to 3.72%. Compared to free OMW, the bioaccessibility indices (BI%) of individual phenolics were increased through yeast encapsulation, at the end of the intestinal stage, hydroxytyrosol and oleuropein could still be detected in encapsulated samples (BI% of 14-25 and 124-189%), but not in free OMW. Thus, YCs could be considered suitable encapsulating agents and show promising characteristics for technological application.

Olive phenols preserve lamin B1 expression reducing cGAS/STING/NFκB-mediated SASP in ionizing radiation-induced senescence.

Senescence occurs upon critical telomere shortening, or following DNA damage, oncogenic activation, hypoxia and oxidative stress, overall referred to stress‐induced premature senescence (SIPS). In response to DNA damage, senescent cells release cytoplasmic chromatin fragments (CCFs), and express an altered secretome, the senescence‐associated secretory phenotype (SASP), which contributes to generate a pro‐inflammatory and pro‐tumoral extracellular milieu. Polyphenols have gained significant attention owing to their anti‐inflammatory and anti‐tumour activities. Here, we studied the effect of oleuropein aglycone (OLE) and hydroxytyrosol (HT) on DNA damage, CCF appearance and SASP in a model of irradiation‐induced senescence. Neonatal human dermal fibroblasts (NHDFs) were γ‐irradiated and incubated with OLE, 5 µM and HT, 1 µM. Cell growth and senescence‐associated (SA)‐β‐Gal‐staining were used as senescence markers. DNA damage was evaluated by Comet assay, lamin B1 expression, release of CCFs, cyclic GMP‐AMP Synthase (cGAS) activation. IL‐6, IL‐8, MCP‐1 and RANTES were measured by ELISA assay. Our results showed that OLE and HT exerted a protective effect on 8 Gy irradiation‐induced senescence, preserving lamin B1 expression and reducing cGAS/STING/NFκB‐mediated SASP. The ability of OLE and HT to mitigate DNA damage, senescence status and the related SASP in normal cells can be exploited to improve the efficacy and safety of cancer radiotherapy.

An Easy-to-Use Procedure for the Measurement of Total Phenolic Compounds in Olive Fruit.

Virgin olive oil (VOO) is one of the most emblematic products of the Mediterranean diet. Its content in phenolic compounds is strongly associated with the antioxidant and health-promoting properties of this diet. VOO’s phenolic profile is determined mainly by the phenolic compounds present in the olive fruit, so knowing their content allows for a fairly precise estimate of the antioxidant and functional properties of the corresponding oil. In this sense, a convenient, green, and sensitive spectrophotometric method was developed for the quantitative determination of total phenolic compounds in olive fruits. The method is based on an easy-to-use extraction procedure of olive fruit phenolics using dimethyl sulfoxide and quantification with the Folin–Ciocalteu reagent. Oleuropein proved to be a suitable reference compound for quantification, displaying a good linear response (r = 0.9996) over the concentration range of 0.58–6.48 mg/mL, with a variation coefficient of 0.42% and limits of detection and quantification of 0.0492 and 0.1490 mg/mL, respectively. The method was validated using a wide array of fruit samples representative of the Olea europaea L. genetic diversity. The results obtained with this spectrophotometric method, expressed as mg/mL of oleuropein, showed a good correlation with those obtained with the fruit samples analyzed by high performance liquid chromatography, with an r value of 0.9930 and a slope value of 1.022, confirming its reliability. Thus, this method can become a very useful simple tool to estimate the total phenolic content of olive fruits, especially when working with numerous samples such as in olive breeding programs or in commercial olive production, in which it is especially useful to know the phenolic state of the fruit and thus determine the optimal harvest date or the most appropriate agronomic treatment to increase the functional properties of the olive fruit and the olive oil.

The antiinflammatory and antifibrotic effect of olive phenols and Lactiplantibacillus plantarum IMC513 in dextran sodium sulfate–induced chronic colitis

Objectives: After a chronic intestinal injury, several intestinal cells switch their phenotype to activated myofibroblasts, which in turn release an abnormal amount of extracellular matrix proteins, leading to the onset of the fibrotic process. To date, no resolutive pharmacological treatments are available, and the identification of new therapeutic approaches represents a crucial goal to achieve. The onset, maintenance, and progression of inflammatory bowel disease are related to abnormal intestinal immune responses to environmental factors, including diet and intestinal microflora components. This study aimed to evaluate the potential antiinflammatory and antifibrotic effect of a biologically debittered olive cream and its probiotic oral administration in an experimental model of dextran sodium sulfate (DSS)–induced chronic colitis.Methods: Chronic colitis was induced in mice by three cycles of oral administration of 2.5% DSS (5 d of DSS followed by 7 d of tap water). Mice were randomly divided into five groups: 10 control mice fed with standard diet (SD), 20 mice receiving SD and DSS (SD+DSS), 20 mice receiving an enriched diet (ED) with olive cream and DSS (ED+DSS), 20 mice receiving SD plus probiotics (PB; Lactiplantibacillus plantarum IMC513) and DSS (SD+PB+DSS), and 20 mice receiving ED plus PB and DSS (ED+ PB+DSS). Clinical features and large bowel macroscopic, histologic, and immunohistochemical findings were evaluated.Results: The simultaneous administration of ED and PB induced a significant reduction in macroscopic and microscopic colitis scores compared with the other DSS-treated groups. In addition, ED and PB led to a significant decrease in the expression of inflammatory cytokines and profibrotic molecules.Conclusions: The concomitant oral administration of a diet enriched with biologically debittered olive cream and a specific probiotic strain (Lactiplantibacillus plantarum IMC513) can exert synergistic antiinflammatory and antifibrotic action in DSS-induced chronic colitis. Further studies are needed to define the cellular and molecular mechanisms modulated by olive cream compounds and by Lactiplantibacillus plantarum IMC513.

One-Step Extraction of Olive Phenols from Aqueous Solution Using β-Cyclodextrin in the Solid State, a Simple Eco-Friendly Method Providing Photochemical Stability to the Extracts.

The extraction of phenolic compounds from olive mill wastes is important, not only to avoid environmental damages, but also because of the intrinsic value of those biophenols, well-known for their high antioxidant potential and health benefits. This study focuses on tyrosol (Tyr) and hydroxytyrosol (HT), two of the main phenolic compounds found in olive mill wastes. A new, simple, and eco-friendly extraction process for the removal of phenolic compounds from aqueous solutions using native β-cyclodextrin (β-CD) in the solid state has been developed. Several β-CD/biophenol molar ratios and biophenol concentrations were investigated, in order to maintain β-CD mostly in the solid state while optimizing the extraction yield and the loading capacity of the sorbent. The extraction efficiencies of Tyr and HT were up to 61%, with a total solid recovery higher than 90% using an initial concentration of 100 mM biophenol and 10 molar equivalents of β-CD. The photochemical stability of the complexes thus obtained was estimated from ∆E*ab curve vs. illumination time. The results obtained showed that the phenols encapsulated into solid β-CD are protected against photodegradation. The powder obtained could be directly developed as a safe-grade food supplement. This simple eco-friendly process could be used for extracting valuable biophenols from olive mill wastewater.

A New Definition of the Term "High-Phenolic Olive Oil" Based on Large Scale Statistical Data of Greek Olive Oils Analyzed by qNMR.

In the last few years, a new term, “High-phenolic olive oil”, has appeared in scientific literature and in the market. However, there is no available definition of that term regarding the concentration limits of the phenolic ingredients of olive oil. For this purpose, we performed a large-scale screening and statistical evaluation of 5764 olive oil samples from Greece coming from >30 varieties for an eleven-year period with precisely measured phenolic content by qNMR. Although there is a large variation among the different cultivars, the mean concentration of total phenolic content was 483 mg/kg. The maximum concentration recorded in Greece reached 4003 mg/kg. We also observed a statistically significant correlation of the phenolic content with the harvest period and we also identified varieties affording olive oils with higher phenolic content. In addition, we performed a study of phenolic content loss during usual storage and we found an average loss of 46% in 12 months. We propose that the term high-phenolic should be used for olive oils with phenolic content > 500 mg/kg that will be able to retain the health claim limit (250 mg/kg) for at least 12 months after bottling. The term exceptionally high phenolic olive oil should be used for olive oil with phenolic content > 1200 mg/kg (top 5%).

Thyroid-Modulating Activities of Olive and Its Polyphenols: A Systematic Review.

Olive oil, which is commonly used in the Mediterranean diet, is known for its health benefits related to the reduction of the risks of cancer, coronary heart disease, hypertension, and neurodegenerative disease. These unique properties are attributed to the phytochemicals with potent antioxidant activities in olive oil. Olive leaf also harbours similar bioactive compounds. Several studies have reported the effects of olive phenolics, olive oil, and leaf extract in the modulation of thyroid activities. A systematic review of the literature was conducted to identify relevant studies on the effects of olive derivatives on thyroid function. A comprehensive search was conducted in October 2020 using the PubMed, Scopus, and Web of Science databases. Cellular, animal, and human studies reporting the effects of olive derivatives, including olive phenolics, olive oil, and leaf extracts on thyroid function were considered. The literature search found 445 articles on this topic, but only nine articles were included based on the inclusion and exclusion criteria. All included articles were animal studies involving the administration of olive oil, olive leaf extract, or olive pomace residues orally. These olive derivatives were consistently demonstrated to have thyroid-stimulating activities in euthyroid or hypothyroid animals, but their mechanisms of action are unknown. Despite the positive results, validation of the beneficial health effects of olive derivatives in the human population is lacking. In conclusion, olive derivatives, especially olive oil and leaf extract, could stimulate thyroid function. Olive pomace residue is not suitable for pharmaceutical or health supplementation purposes. Therapeutic applications of olive oil and leaf extract, especially in individuals with hypothyroidism, require further validation through human studies.

Molecular Docking and Molecular Dynamics Aided Virtual Search of OliveNet™ Directory for Secoiridoids to Combat SARS-CoV-2 Infection and Associated Hyperinflammatory Responses.

Molecular docking and molecular dynamics aided virtual search of OliveNet™ directory identified potential secoiridoids that combat SARS-CoV-2 entry, replication, and associated hyperinflammatory responses. OliveNet™ is an active directory of phytochemicals obtained from different parts of the olive tree, Olea europaea (Oleaceae). Olive oil, olive fruits containing phenolics, known for their health benefits, are indispensable in the Mediterranean and Arabian diets. Secoiridoids is the largest group of olive phenols and is exclusive to the olive fruits. Functional food like olive fruits could help prevent and alleviate viral disease at an affordable cost. A systematized virtual search of 932 conformers of 78 secoiridoids utilizing Autodock Vina, followed by precision docking using Idock and Smina indicated that Nüzhenide oleoside (NZO), Oleuropein dimer (OED), and Dihydro oleuropein (DHO) blocked the SARS-CoV-2 spike (S) protein-ACE-2 interface; Demethyloleuropein (DMO), Neo-nüzhenide (NNZ), and Nüzhenide (NZE) blocked the SARS-CoV-2 main protease (Mpro). Molecular dynamics (MD) simulation of the NZO-S-protein-ACE-2 complex by Desmond revealed stability during 50 ns. RMSD of the NZO-S-protein-ACE-2 complex converged at 2.1 Å after 20 ns. During MD, the interaction fractions confirmed multiple interactions of NZO with Lys417, a crucial residue for inhibition of S protein. MD of DMO-Mpro complex proved its stability as the RMSD converged at 1.6 Å. Analysis of interactions during MD confirmed the interaction of Cys145 of Mpro with DMO and, thus, its inhibition. The docking predicted IC50 of NZO and DMO was 11.58 and 6.44 μM, respectively. Molecular docking and dynamics of inhibition of the S protein and Mpro by NZO and DMO correlated well. Docking of the six-hit secoiridoids to IL1R, IL6R, and TNFR1, the receptors of inflammatory cytokines IL1β, IL6, and TNFα, revealed the anti-inflammatory potential except for DHO. Due to intricate structures, the secoiridoids violated Lipinski's rule of five. However, the drug scores of secoiridoids supported their use as drugs. The ADMET predictions implied that the secoiridoids are non-toxic and pose low oral absorption. Secoiridoids need further optimization and are a suitable lead for the discovery of anti-SARS-CoV-2 therapeutics. For the moment, olive secoiridoids presents an accessible mode of prevention and therapy of SARS-CoV-2 infection.

Improving the storage stability of tomato paste by the addition of encapsulated olive leaf phenolics and experimental growth modeling of A. flavus

It is necessary to apply some preservatives for tomato paste since in the harvest season, a high load of tomatoes need to be processed as they are among highly perishable products. Application of antimicrobial extracts or essential oils, as natural preservatives, in their raw forms might reduce their efficiency when they are exposed to environmental conditions. However, microencapsulation is a well-known method to solve this problem. Our main goal was to restrict fungal growth rate in stored tomato paste and increase its storage stability by incorporating encapsulated olive leaf phenolic-rich extract. Total Soluble Solids (TSS), consistency, pH, color indices and diametrical growth rate of Aspergillus flavus were measured for different samples. The treatments designed in terms of considering two levels of non-encapsulated olive phenolics extract with 500 and 1000 ppm (NE500 and NE1000), the same levels with encapsulated extract; i.e., 500 and 1000 ppm (ME500 and ME1000), and similar levels of the common preservative of sodium benzoate with 500 and 1000 ppm (B500 and B1000). Antifungal properties of NE samples were higher than ME ones during storage although ME samples could maintain diametrical growth rate of the fungus more stable than NE ones. NE samples justified lower maximum growth rate than ME samples while ME samples could extend lag phase of microbial growth compared with NE one and delay their internal deteriorative reactions. Among Baranyi, modified Baranyi, Modified Gompertz, and Logistic models, Modified Gompertz model represented the best model and could fit the growth factors of A. flavus on tomato paste with higher R2 index as well as lower RMSE and SSE indices. Based on the results obtained, it could be concluded that usage of encapsulated olive leaf extract in tomato paste is an effective, natural and sustainable approach to improve the shelf life of tomato paste since this natural compound could perform as favourable as preservatives; also it could maintain physicochemical as well as microbial properties of tomato paste for a long term. Thus, it is strongly recommended that application of encapsulated olive leaf extract to be considered seriously by the tomato paste industry as it can effectively reduce the mold and fungal contaminations which are very common and prevalent in the plants. The future work in this regard should focus on sensory evaluations when incorporating encapsulated olive leaf extract into tomato paste.

The effect of olive leaf extract on cardiovascular health markers: a randomized placebo-controlled clinical trial

PurposeOverweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels.MethodsIn this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m2) with total cholesterol levels of 5.0–8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks.ResultsOLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05).ConclusionsBlood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels.Trial registeredThe trial has been registered at ClinicalTrials.gov (NCT02990637).

Chromatin modification by olive phenolics: In silico molecular docking studies utilising the phenolic groups categorised in the OliveNet™ database against lysine specific demethylase enzymes

Extra virgin olive oil is the principal source of dietary fat in the Mediterranean diet and is considered to have beneficial health effects. There is evidence to suggest that the phenolic compounds within Olea europaea have the ability to inhibit lysine-specific demethylase 1 (LSD1). This is an epigenetic enzyme that removes methyl groups from histone proteins and regulates gene transcription. Conversely, SET domain-containing protein 7 (SETD7) has opposing enzymatic activity and is a histone methyltransferase. Due to the involvement of these proteins in a number of pathological processes, including cancer and diabetes, further research needs to be conducted into the way in which they can be targeted. A large number of phenolic compounds (>200) have been identified in Olea europaea. To help expedite the discovery of promising lead compounds, in this study, in silico molecular docking methods were used to investigate the molecular binding properties of the phenolic compounds obtained from the OliveNet™ database to LSD1 and its variants, LSD2, and SETD7. Numerous Olea europaea phenolic compounds were predicted to bind to the epigenetic enzymes and several had stronger binding affinities than the LSD1 and SETD7 positive control inhibitors. The protein-ligand interactions of the phenolic compounds were also compared to known inhibitors and the molecular docking results suggest that the flavonoids, secoiridoids and glucosides may bind particularly strongly to the epigenetic regulators. Overall, several ligands were identified as lead compounds from this research and their potential inhibitory activity could be validated further in the laboratory.