Oleocanthal

Beneficial effects of olive oil and Mediterranean diet on cancer physio-pathology and incidence.[Pubmed:33249203]

Semin Cancer Biol. 2020 Nov 26. pii: S1044-579X(20)30247-9.

Virgin olive oil is a characteristic component and the main source of fat of the Mediterranean diet. It is a mix of high-value health compounds, including monounsaturated fatty acids (mainly oleic acid), simple phenols (such as hydroxytyrosol and tyrosol), secoiridoids (such as oleuropein, Oleocanthal), flavonoids, and terpenoids (such as squalene). Olive oil consumption has been shown to improve different aspects of human health and has been associated with a lower risk of cancer. However, the underlying cellular mechanisms involved in such effects are still poorly defined, but seem to be related to a promotion of apoptosis, modulation of epigenetic patterns, blockade of cell cycle, and angiogenesis regulation. The aim of this review is to update the current associations of cancer risk with the Mediterranean diet, olive oil consumption and its main components. In addition, the identification of key olive oil components involved in anticarcinogenic mechanisms and pathways according to experimental models is also addressed.

Characterization of Phenolic Compounds, Vitamin E and Fatty Acids from Monovarietal Virgin Olive Oils of "Picholine marocaine" Cultivar.[Pubmed:33228191]

Molecules. 2020 Nov 19;25(22). pii: molecules25225428.

Olive oil is an important product in the Mediterranean diet, due to its health benefits and sensorial characteristics. Picholine marocaine is the most cultivated variety in Morocco. The present research aims to evaluate the phenolic compounds, vitamin E and fatty acids of commercial Picholine marocaine virgin olive oils (VOOs) from five different North Moroccan provinces (Chefchaouen, Taounate, Errachidia, Beni Mellal and Taza), using HPLC-photodiode array (PDA)/electrospray ionization (ESI)-MS, normal phase (NP)-HPLC/ fluorescence detector (FLD) and GC-flame ionization detector (FID)/MS, respectively. The obtained results showed an average content of 130.0 mg kg(-1) of secoiridoids (oleuropein aglycone, 10-hydroxy-oleuropein aglycone and ligstroside aglycone, Oleocanthal and oleacein), 108.1 mg kg(-1) of phenolic alcohols (tyrosol and hydroxytyrosol), 34.7 mg kg(-1) of phenolic acids (caffeic acid, ferulic acid and elenolic acid), and 8.24 mg kg(-1) of flavonoids (luteolin, luteolin glucoside, apigenin). With regard to vitamin E, alpha-tocopherol was the most abundant vitamin E (57.9 mg kg(-1)), followed by alpha-tocotrienol (2.5 mg kg(-1)), gamma-tocopherol (4.5 mg kg(-1)) and beta-tocopherol (1.9 mg kg(-1)), while delta-tocopherol was not detected. Moreover, 14 fatty acids were found and, among them, oleic acid (76.1%), linoleic acid (8.1%) palmitic acid (8.7%) and stearic acid (2.5%) were the major fatty acids detected. Finally, heat map and principal component analysis allowed us to classify the studied provinces in terms of VOO chemical composition: Chefchaouen (tyrosol and hydroxytyrosol), Taounate (oleuropein aglycone), Errachidia (ferulic acid, w-3 and w-6), Beni Mellal (Oleocanthal) and Taza (luteolin and oleic acid).

Insight into the Storage-Related Oxidative/Hydrolytic Degradation of Olive Oil Secoiridoids by Liquid Chromatography and High-Resolution Fourier Transform Mass Spectrometry.[Pubmed:33103891]

J Agric Food Chem. 2020 Nov 4;68(44):12310-12325.

The study of negative effects potentially exerted by the exposure to oxygen and/or light and, thus, also by the type of container on the quality of extra virgin olive oil (EVOO) during its prolonged storage requires an appropriate choice of analytical methods and components to be monitored. Here, reverse-phase liquid chromatography coupled to high-resolution/accuracy Fourier transform mass spectrometry with electrospray ionization was exploited to study oxidative/hydrolytic degradation processes occurring on the important bioactive components of EVOO known as secoiridoids, i.e., oleuropein and ligstroside aglycones, oleacin, and Oleocanthal, during storage up to 6 months under controlled conditions. Specifically, isomeric oxidative byproducts resulting from the transformation of a carbonylic group of the original secoiridoids into a carboxylic group and compounds resulting from hydrolysis of the ester linkage of secoiridoids, i.e., elenolic and decarboxymethyl elenolic acids and tyrosol and 3-hydroxytyrosol, were monitored, along with their precursors. Data obtained from EVOO storage at room temperature in glass bottles with/without exposure to light and/or oxygen indicated that, although it was more relevant if a periodical exposure to oxygen was performed, a non-negligible oxidative degradation occurred on secoiridoids also when nitrogen was used to saturate the container headspace. In a parallel experiment, the effects of storage of the same EVOO (250 mL) for up to 6 months in containers manufactured with different materials/shapes were considered. In particular, a square dark glass bottle, a stainless-steel can, and a ceramic jar, typically used for EVOO commercialization, and a clear polyethylene terephthalate bottle, purposely chosen to prompt secoiridoid degradation through exposure to light and oxygen, were compared. Dark glass was found to provide the best combined protection of major secoiridoids from oxidative and hydrolytic degradation, yet the lowest levels of oxidized byproducts were observed when the stainless-steel can was used.

Conservation of Native Wild Ivory-White Olives from the MEDES Islands Natural Reserve to Maintain Virgin Olive Oil Diversity.[Pubmed:33080812]

Antioxidants (Basel). 2020 Oct 17;9(10). pii: antiox9101009.

Food diversity, and in particular genetic diversity, is being lost at an alarming rate. Protection of natural areas is crucial to safeguard the world's threatened species. The Medes Islands (MI), located in the northwest Mediterranean Sea, are a protected natural reserve. Wild olive trees also known as oleasters make up part of the vegetation of the Meda Gran island. Among them, in 2012, a wild albino ivory-white olive tree with fruit was identified. Fruits were collected from this tree and their seeds were first sown in a greenhouse and then planted in an orchard for purposes of ex situ preservation. Seven out of the 78 seedling trees obtained (12%) produced ivory-white fruits. In autumn 2018, fruits from these trees were sampled. Although the fruits had low oil content, virgin olive oil with unique sensory, physicochemical, and stability characteristics was produced. With respect to the polyphenols content, oleacein was the main compound identified (373.29 +/- 72.02 mg/kg) and the Oleocanthal was the second most abundant phenolic compound (204.84 +/- 52.58 mg/kg). Regarding pigments, samples were characterized by an intense yellow color, with 12.5 +/- 4.6 mg/kg of chlorophyll and 9.2 +/- 3.3 mg/kg of carotenoids. Finally, oleic acid was the main fatty acid identified. This study explored the resources of the natural habitat of the MI as a means of enrichment of olive oil diversity and authenticity of this traditional Mediterranean food.

Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study.[Pubmed:33023123]

Metabolites. 2020 Oct 2;10(10). pii: metabo10100392.

Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound Oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 +/- 11 years) for 2 months. Anthropometric data, metabolic parameters, hepatic steatosis (by fatty liver index, FLI), abdominal fat distribution (by ultrasound), and pro- and anti-inflammatory cytokines were assessed before and after the intervention. EVOO supplementation was associated with a reduction in body weight, waist circumference, body mass index (BMI), alanine transaminase and FLI, as well as interleukin (IL)-6, IL-17A, tumor necrosis factor-alpha and IL-1B, while IL-10 increased. Maximum subcutaneous fat thickness (SFT max) also increased, with a concomitant decrease in the ratio of visceral fat layer thickness/SFT max. Correlation analysis revealed positive associations between changes in body weight and BMI and those in SFT max, along with an inverse association between changes in IL-6 and those in SFT max. In conclusion, ingestion of EVOO with a high OC concentration had beneficial effects on metabolic parameters, inflammatory cytokines and abdominal fat distribution in MetS subjects with hepatic steatosis, a category of patients at high cardiometabolic risk.

The Inhibitory Effect of Extra Virgin Olive Oil and Its Active Compound Oleocanthal on Prostaglandin-Induced Uterine Hypercontraction and Pain-Ex Vivo and In Vivo Study.[Pubmed:33008039]

Nutrients. 2020 Sep 30;12(10). pii: nu12103012.

Primary dysmenorrhea is a common occurrence in adolescent women and is a type of chronic inflammation. Dysmenorrhea is due to an increase in oxidative stress, which increases cyclooxygenase-2 (COX-2) expression, increases the concentration of prostaglandin F2alpha (PGF2alpha), and increases the calcium concentration in uterine smooth muscle, causing excessive uterine contractions and pain. The polyphenolic compound Oleocanthal (OC) in extra virgin olive oil (EVOO) has been shown to have an anti-inflammatory and antioxidant effect. This study aimed to investigate the inhibitory effect of extra virgin olive oil and its active ingredient Oleocanthal (OC) on prostaglandin-induced uterine hyper-contraction, its antioxidant ability, and related mechanisms. We used force-displacement transducers to calculate uterine contraction in an ex vivo study. To analyze the analgesic effect, in an in vivo study, we used an acetic acid/oxytocin-induced mice writhing model and determined uterus contraction-related signaling protein expression. The active compound OC inhibited calcium/PGF2alpha-induced uterine hyper-contraction. In the acetic acid and oxytocin-induced mice writhing model, the intervention of the EVOO acetonitrile layer extraction inhibited pain by inhibiting oxidative stress and the phosphorylation of the protein kinase C (PKC)/extracellular signal-regulated kinases (ERK)/ myosin light chain (MLC) signaling pathway. These findings supported the idea that EVOO and its active ingredient, OC, can effectively decrease oxidative stress and PGF2alpha-induced uterine hyper-contraction, representing a further treatment for dysmenorrhea.

A review on management of cardiovascular diseases by olive polyphenols.[Pubmed:32994927]

Food Sci Nutr. 2020 Aug 13;8(9):4639-4655.

Noncommunicable diseases have increasingly grown the cause of morbidities and mortalities worldwide. Among them, cardiovascular diseases (CVDs) continue to be the major contributor to deaths. CVDs are common in the urban community population due to the substandard living conditions, which have a significant impact on the healthcare system, and over 23 million human beings are anticipated to suffer from the CVDs before 2030. At the moment, CVD physicians are immediately advancing both primary and secondary prevention modalities in high-risk populations. The cornerstone of CVD prevention is a healthy lifestyle that is more cost-effective than the treatments after disease onset. In fact, in the present scenario, comprehensive research conducted on food plant components is potentially efficacious in reducing some highly prevalent CVD risk factors, such as hypercholesterolemia, hypertension, and atherosclerosis. Polyphenols of olive oil (OO), virgin olive oil (VOO), and extra virgin olive oil contribute an essential role for the management of CVDs. Olive oil induces cardioprotective effects due to the presence of a plethora of polyphenolic compounds, for example, oleuropein (OL), tyrosol, and hydroxytyrosol. The present study examines the bioavailability and absorption of major olive bioactive compounds, for instance, oleacein, Oleocanthal, OL, and tyrosol. This review also elucidates the snobbish connection of olive polyphenols (OP) and the potential mechanism involved in combating various CVD results taken up from the in vitro and in vivo studies, such as animal and human model studies.

In silico characterisation of olive phenolic compounds as potential cyclooxygenase modulators. Part 2.[Pubmed:32920237]

J Mol Graph Model. 2020 Dec;101:107743.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, and function by targeting cyclooxygenase (COX) enzymes to inhibit the production of prostaglandins that facilitate inflammation. Since Oleocanthal derived from Olea europaea is known to inhibit COX, we sought to characterise novel olive compounds with COX inhibitory activity using in silico techniques. Following on from part 1 of this study which identified 1-oleyltyrosol (1OL) and ligstroside derivative 2 (LG2) with COX inhibitory potential, the mechanisms of COX interactions by these selected compounds were further examined using molecular dynamics (MD) simulations. Classical MD simulations were carried out on COX-1 and COX-2 complexed with 1OL and LG2 to determine the stability and protein backbone fluctuation. Protein dynamics were examined using essential dynamics methods and network analysis, which identified that the N-terminal epidermal growth factor-like domain and membrane bound domains of COX-1 and -2 exhibited altered motions when ligands were bound. Distinct dynamical modules were identified, and that COX-2 inter-residue communications were more sensitive to ligand binding compared to COX-1. The use of various network metrics presents a novel approach in the characterisation of network behaviour of different ligands. It is proposed that inter-residue network metrics provide additional measures of the potential bioactivity of ligands, which may form a useful adjunct to conventional direct predictions of binding affinity, in determining the efficacy of potential small-molecule inhibitors. Overall, this two-part study characterises anti-inflammatory effects of low dosage dietary COX inhibitors, and provides a possible avenue for the development of therapeutics in inflammatory diseases.

A Quantitative Phytochemical Comparison of Olive Leaf Extracts on the Australian Market.[Pubmed:32911652]

Molecules. 2020 Sep 8;25(18). pii: molecules25184099.

Olive leaf extract (OLE), prepared from the fresh or dried leaves of Olea europaea L., is generating interest as a cardiovascular and metabolic disease risk modifier. Positive effects for the leaf extract and its key phytochemical constituents have been reported on blood pressure, respiratory infections, inflammation, and insulin resistance. A variety of OLE products are available both over-the-counter and for professional dispensing. The aim of this research was to quantitatively explore the phytochemical profile of different OLE products on the Australian market. Ten OLE products available on the Australian market (five over-the-counter products and five products for professional compounding and dispensing) were quantitatively analyzed for oleuropein, hydroxytyrosol, oleacein, Oleocanthal, total biophenols, maslinic acid, and oleanolic acid, using high-performance liquid chromatography (HPLC). Substantial variation in oleuropein and hydroxytyrosol levels was noted between extracts, with a trend towards higher oleuropein and lower hydroxytyrosol levels being noted in products produced using the fresh olive leaf as opposed to dry olive leaf. These results suggest that OLE products on the Australian market vary substantially in their phytochemical profiles. Products for professional compounding and dispensing in many cases contained less oleuropein than over-the-counter products, but more hydroxytyrosol and comparable total biophenol levels.

In silico characterisation of olive phenolic compounds as potential cyclooxygenase modulators. Part 1.[Pubmed:32898836]

J Mol Graph Model. 2020 Dec;101:107719.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce pain. These target cyclooxygenase (COX) enzymes which produce inflammatory mediators. Adverse effects associated with the use of traditional NSAIDs have led to a rise in the development of alternative therapies. Derived from Olea Europaea, olive oil is a main component of the Mediterranean diet, containing phenolic compounds that contribute to its antioxidant and anti-inflammatory properties. It has previously been found that Oleocanthal, a phenolic compound derived from the olive, had similar effects to ibuprofen, a commonly used NSAID. There is an abundance of olive phenolic compounds that have yet to be investigated for their anti-inflammatory properties. In this study, it was sought to identify potential olive-derived compounds with the ability to inhibit COX enzymes, and study the mechanisms using in silico approaches. Molecular docking was employed to determine the COX inhibitory potential of an olive phenolic compound library. From docking, it was determined that 1-oleyltyrosol (1OL) and ligstroside derivative 2 (LG2) demonstrated the greatest binding affinity to both COX-1 and COX-2. Interactions with these compounds were further examined using molecular dynamics simulations. The residue contributions to binding free energy were computed using Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) methods, revealing that residues Leu93, Val116, Leu352, and Ala527 in COX-1 and COX-2 were key determinants of potential inhibition. Along with part 2 of this study, this work aims to identify and characterise novel phenolic compounds which may possess COX inhibitory properties.

Green Route for the Isolation and Purification of Hyrdoxytyrosol, Tyrosol, Oleacein and Oleocanthal from Extra Virgin Olive Oil.[Pubmed:32796621]

Molecules. 2020 Aug 11;25(16). pii: molecules25163654.

Extra virgin olive oil (EVOO) phenols represent a significant part of the intake of antioxidants and bioactive compounds in the Mediterranean diet. In particular, hydroxytyrosol (HTyr), tyrosol (Tyr), and the secoiridoids oleacein and Oleocanthal play central roles as anti-inflammatory, neuro-protective and anti-cancer agents. These compounds cannot be easily obtained via chemical synthesis, and their isolation and purification from EVOO is cumbersome. Indeed, both processes involve the use of large volumes of organic solvents, hazardous reagents and several chromatographic steps. In this work we propose a novel optimized procedure for the green extraction, isolation and purification of HTyr, Tyr, oleacein and Oleocanthal directly from EVOO, by using a Natural Deep Eutectic Solvent (NaDES) as an extracting phase, coupled with preparative high-performance liquid chromatography. This purification method allows the total recovery of the four components as single pure compounds directly from EVOO, in a rapid, economic and ecologically sustainable way, which utilizes biocompatible reagents and strongly limits the use or generation of hazardous substances.

The decrease in the health benefits of extra virgin olive oil during storage is conditioned by the initial phenolic profile.[Pubmed:32768900]

Food Chem. 2021 Jan 30;336:127730.

Phenols are responsible for the only health claim of virgin olive oil (VOO) recognized by the European Commission EU 432/2012 and the European Food Safety Authority. In this research, we studied the decrease in the phenolic content of 160 extra VOOs (EVOOs) after 12 months storage in darkness at 20 degrees C. Phenolic concentration was decreased 42.0 +/- 24.3% after this period and this reduction strongly depended on the initial phenolic profile. Hence, EVOOs with predominance in oleacein and Oleocanthal experienced a larger decrease in phenolic content than oils enriched in other phenols. Complementarily, hydroxytyrosol and Oleocanthalic acid increased significantly in aged EVOOs, which allowed their discrimination from recently produced EVOOs. These changes are explained by degradation of main secoiridoids during storage due to their antioxidant properties. Hydroxytyrosol and Oleocanthalic acid can be considered markers of olive oil ageing, although they can also provide information about quality or stability.

Comment on Lopez-Yerena et al. "Absorption and Intestinal Metabolic Profile of Oleocanthal in Rats" Pharmaceutics 2020, 12, 134.[Pubmed:32751928]

Pharmaceutics. 2020 Jul 31;12(8). pii: pharmaceutics12080720.

This comment is intended to discuss errors observed in the title paper, doi:10.3390/pharmaceutics12020134. When this paper was published, the authors of this commentary were excited to read it. However, the more we read, the more pitfalls were observed, which necessitated a response to revise the many errors and misleading information included in this publication.

The Emerging Role of Nutraceuticals and Phytochemicals in the Prevention and Treatment of Alzheimer's Disease.[Pubmed:32651325]

J Alzheimers Dis. 2020;77(1):33-51.

One of the major challenges of medical sciences has been finding a reliable compound for the pharmacological treatment of Alzheimer's disease (AD). As most of the drugs directed to a variety of targets have failed in finding a medical solution, natural products from Ayurvedic medicine or nutraceutical compounds emerge as a viable preventive therapeutics' pathway. Considering that AD is a multifactorial disease, nutraceutical compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs used for AD treatment. We review in-depth important medicinal plants that have been already investigated for therapeutic uses against AD, focusing on a diversity of pharmacological actions. These targets include inhibition of acetylcholinesterase, beta-amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc., and pharmacological actions so diverse as anti-inflammatory, memory enhancement, nootropic effects, glutamate excitotoxicity, anti-depressants, and antioxidants. In addition, we also discuss the activity of nutraceutical compounds and phytopharmaceuticals formulae, mainly directed to tau protein aggregates mechanisms of action. These include compounds such as curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, Oleocanthal, and meganatural-az and other phytochemicals such as huperzine A, limonoids, azaphilones, and aged garlic extract. Finally, we revise the nutraceutical formulae BrainUp-10 composed of Andean shilajit and B-complex vitamins, with memory enhancement activity and the control of neuropsychiatric distress in AD patients. This integrated view on nutraceutical opens a new pathway for future investigations and clinical trials that are likely to render some results based on medical evidence.