Capillary electrophoresis-electrospray ionization-mass spectrometry method to determine the phenolic fraction of extra-virgin olive oil.

PubMed

Carrasco-Pancorbo, Alegría; Arráez-Román, David; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

2006-06-01

We describe the first analytical method involving SPE and CZE coupled to ESI-IT MS (CZE-ESI-MS) used to identify and characterize phenolic compounds in olive oil samples. The SPE, CZE and ESI-MS parameters were optimized in order to maximize the number of phenolic compounds detected and the sensitivity of their determination. To this end we have devised a detailed method to find the best conditions for CE separation and the detection by MS of the phenolic compounds present in olive oil using a methanol-water extract of Picual extra-virgin olive oil (VOO). Electrophoretic separation was carried out using an aqueous CE buffer system consisting of 60 mM NH(4)OAc at pH 9.5 with 5% of 2-propanol, a sheath liquid containing 2-propanol/water 60:40 v/v and 0.1% v/v triethylamine. This method offers to the analyst the chance to study important phenolic compounds such as phenolic alcohols (tyrosol (TY), hydroxytyrosol (HYTY) and 2-(4-hydroxyphenyl)ethyl acetate), lignans ((+)-pinoresinol and (+)-1-acetoxypinoresinol), complex phenols (ligstroside aglycon (Lig Agl), oleuropein aglycon, their respective decarboxylated derivatives and several isomeric forms of these (dialdehydic form of oleuropein aglycon, dialdehydic form of ligstroside aglycon, dialdehydic form of decarboxymethyl elenolic acid linked to HYTY, dialdehydic form of decarboxymethyl elenolic acid linked to TY) and 10-hydroxy-oleuropein aglycon) and one other phenolic compound (elenolic acid) in extra-VOO by using a simple SPE before CE-ESI-MS analysis.

Enzymatic tailoring of oleuropein from Olea europaea leaves and product identification by HRMS/MS spectrometry.

PubMed

Nikolaivits, Efstratios; Termentzi, Aikaterini; Skaltsounis, Alexios-Leandros; Fokialakis, Nikolas; Topakas, Evangelos

2017-07-10

Oleuropein, a bioactive compound found in all parts of olive tree, especially in leaves and branches, presents numerous health promoting properties that increase research and market interest the last few years. In addition, oleuropein degradation products, such as hydroxytyrosol, elenolic acid, and the aglycones also exhibit biological activities with different properties compared to the starting compound. Under this view, a commercial lipase preparation Lipolase 100L and a thermophilic β-glucosidase from Myceliophthora thermophila were used for the regioselective hydrolysis of oleuropein towards the production of the corresponding biologically active compounds. The enzymatic degradation products of oleuropein, such as hydroxytyrosol, elenolic acid and its glucoside, and oleuropein aglycones were identified by LC-HRMS/MS and NMR spectroscopy. The latter, was found as a mix of diastereomers of the monoaldehydic form of oleuropein aglycone, identified as (5S, 8R, 9S)-, (5S, 8S, 9S)- and (5S, 8R, 9R). The high substrate specificity exhibited by both lipase and β-glucosidase allows the successful tailoring of oleuropein towards the production of different biologically active compounds with significant potential in the cosmeceutical and food industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of copper on the antioxidant activity of olive polyphenols in bulk oil and oil-in-water emulsions.

PubMed

Paiva-Martins, Fátima; Santos, Vera; Mangericão, Hugo; Gordon, Michael H

2006-05-17

The antioxidant activity and interactions with copper of four olive oil phenolic compounds, namely oleuropein, hydroxytyrosol, 3,4-dihydroxyphenylethanol-elenolic acid (1), and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (2), in olive oil and oil-in-water emulsions stored at 60 degrees C were studied. All four phenolic compounds significantly extended the induction time of lipid oxidation in olive oil with the order of activity being hydroxytyrosol > compound 1 > compound 2 > oleuropein > alpha-tocopherol; but in the presence of Cu(ll), the stability of oil samples containing phenolic compounds decreased by at least 90%, and the antioxidant activity of hydroxytyrosol and compounds 1 and 2 became similar. In oil-in-water emulsions prepared from olive oil stripped of tocopherols, hydroxytyrosol enhanced the prooxidant effect of copper at pH 5.5 but not at pH 7.4. The stability of samples containing copper at pH 5.5 was not significantly different if oleuropein was present from that of the control. Oleuropein at pH 7.4, and compounds 1 and 2 at both pH values tested, reduced the prooxidant effect of copper. The lower stability and the higher reducing capacity of all compounds at pH 7.4 could not explain the higher stability of emulsions containing phenolic compounds at this pH value. However, mixtures containing hydroxytyrosol or oleuropein with copper showed higher 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity at pH 7.4 than at pH 5.5. Moreover, the compound 2-copper complex showed higher radical scavenging activity then the uncomplexed compound at pH 5.5. It can be concluded that the formation of a copper complex with radical scavenging activity is a key step in the antioxidant action of the olive oil phenolic compounds in an emulsion containing copper ions.

Bioavailability of phenolics from an oleuropein-rich olive (Olea europaea) leaf extract and its acute effect on plasma antioxidant status: comparison between pre- and postmenopausal women.

PubMed

García-Villalba, R; Larrosa, M; Possemiers, S; Tomás-Barberán, F A; Espín, J C

2014-06-01

Preclinical studies suggest a potential protective effect of oleuropein in osteoporosis, and one of the proposed mechanisms is the modulation of the oxidative stress. Oleuropein bioavailability and its effect on antioxidant status in pre- and postmenopausal women are unknown. The aim of the present study was to investigate the oral bioavailability of an olive leaf extract rich in oleuropein (40 %) and its effect on antioxidant status in postmenopausal women compared to premenopausal women. Premenopausal (n = 8) and postmenopausal women (n = 8) received 250 mg of olive leaf extract, blood samples (t = 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 h) were taken, and 24-h urine divided into five fractions was collected. Olive-leaf-extract-derived metabolites were analyzed in plasma and urine by HPLC-ESI-QTOF and UPLC-ESI-QqQ, and pharmacokinetics parameters were determined. Ferric reducing antioxidant ability and malondialdehyde levels were measured in plasma. Plasma levels of hydroxytyrosol glucuronide, hydroxytyrosol sulfate, oleuropein aglycon glucuronide and oleuropein aglycon derivative 1 were higher in postmenopausal women. MDA levels were significantly decreased (32%) in postmenopausal women and inversely correlated with hydroxytyrosol sulfate levels. Postmenopausal women excreted less sulfated metabolites in urine than premenopausal women. Our results suggest that postmenopausal women could be a target population for the intake of olive phenolics in order to prevent age-related and oxidative stress-related processes such as osteoporosis.

A comprehensive evaluation of tyrosol and hydroxytyrosol derivatives in extra virgin olive oil by microwave-assisted hydrolysis and HPLC-MS/MS.

PubMed

Bartella, Lucia; Mazzotti, Fabio; Napoli, Anna; Sindona, Giovanni; Di Donna, Leonardo

2018-03-01

A rapid and reliable method to assay the total amount of tyrosol and hydroxytyrosol derivatives in extra virgin olive oil has been developed. The methodology intends to establish the nutritional quality of this edible oil addressing recent international health claim legislations (the European Commission Regulation No. 432/2012) and changing the classification of extra virgin olive oil to the status of nutraceutical. The method is based on the use of high-performance liquid chromatography coupled with tandem mass spectrometry and labeled internal standards preceded by a fast hydrolysis reaction step performed through the aid of microwaves under acid conditions. The overall process is particularly time saving, much shorter than any methodology previously reported. The developed approach represents a mix of rapidity and accuracy whose values have been found near 100% on different fortified vegetable oils, while the RSD% values, calculated from repeatability and reproducibility experiments, are in all cases under 7%. Graphical abstract Schematic of the methodology applied to the determination of tyrosol and hydroxytyrosol ester conjugates.

Olive-oil consumption and health: the possible role of antioxidants.

PubMed

Owen, R W; Giacosa, A; Hull, W E; Haubner, R; Würtele, G; Spiegelhalder, B; Bartsch, H

2000-10-01

In the Mediterranean basin, olive oil, along with fruits, vegetables, and fish, is an important constituent of the diet, and is considered a major factor in preserving a healthy and relatively disease-free population. Epidemiological data show that the Mediterranean diet has significant protective effects against cancer and coronary heart disease. We present evidence that it is the unique profile of the phenolic fraction, along with high intakes of squalene and the monounsaturated fatty acid, oleic acid, which confer its health-promoting properties. The major phenolic compounds identified and quantified in olive oil belong to three different classes: simple phenols (hydroxytyrosol, tyrosol); secoiridoids (oleuropein, the aglycone of ligstroside, and their respective decarboxylated dialdehyde derivatives); and the lignans [(+)-1-acetoxypinoresinol and pinoresinol]. All three classes have potent antioxidant properties. High consumption of extra-virgin olive oils, which are particularly rich in these phenolic antioxidants (as well as squalene and oleic acid), should afford considerable protection against cancer (colon, breast, skin), coronary heart disease, and ageing by inhibiting oxidative stress.

Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation.

PubMed

Kitsati, Natalia; Mantzaris, Michalis D; Galaris, Dimitrios

2016-12-01

Although it is known that Mediterranean diet plays an important role in maintaining human health, the underlying molecular mechanisms remain largely unknown. The aim of this investigation was to elucidate the potential role of ortho-dihydroxy group containing natural compounds in H 2 O 2 -induced DNA damage and apoptosis. For this purpose, the main phenolic alcohols of olive oil, namely hydroxytyrosol and tyrosol, were examined for their ability to protect cultured cells under conditions of oxidative stress. A strong correlation was observed between the ability of hydroxytyrosol to mitigate intracellular labile iron level and the protection offered against H 2 O 2 -induced DNA damage and apoptosis. On the other hand, tyrosol, which lacks the ortho-dihydroxy group, was ineffective. Moreover, hydroxytyrosol (but not tyrosol), was able to diminish the late sustained phase of H 2 O 2 -induced JNK and p38 phosphorylation. The derangement of intracellular iron homeostasis, following exposure of cells to H 2 O 2 , played pivotal role both in the induction of DNA damage and the initiation of apoptotic signaling. The presented results suggest that the protective effects exerted by ortho-dihydroxy group containing dietary compounds against oxidative stress-induced cell damage are linked to their ability to influence changes in the intracellular labile iron homeostasis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Oleuropein hydrolysis in natural green olives: Importance of the endogenous enzymes.

PubMed

Ramírez, Eva; Brenes, Manuel; García, Pedro; Medina, Eduardo; Romero, Concepción

2016-09-01

The bitter taste of olives is mainly caused by the phenolic compound named oleuropein and the mechanism of its hydrolysis during the processing of natural green olives was studied. First, a rapid chemical hydrolysis of oleuropein takes place at a high temperature of 40°C and at a low pH value of 2.8, but the chemical hydrolysis of the bitter compound is slow at the common range of pH for these olives (3.8-4.2). However, decarboxymethyl elenolic acid linked to hydroxytyrosol and hydroxytyrosol have been found in a high concentration during the elaboration of natural green olives. When olives were heated at 90°C for 10min before brining, these compounds are not formed. Hence, the debittering process in natural green olives is due to the activity of β-glucosidase and esterase during the first months of storage and then a slow chemical hydrolysis of oleuropein happens throughout storage time. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fermented Apulian table olives: Effect of selected microbial starters on polyphenols composition, antioxidant activities and bioaccessibility.

PubMed

D'Antuono, Isabella; Bruno, Angelica; Linsalata, Vito; Minervini, Fiorenza; Garbetta, Antonella; Tufariello, Maria; Mita, Giovanni; Logrieco, Antonio F; Bleve, Gianluca; Cardinali, Angela

2018-05-15

The effects of fermentation by autochthonous microbial starters on phenolics composition of Apulian table olives, Bella di Cerignola (BDC), Termite di Bitetto (TDB) and Cellina di Nardò (CEL) were studied, highlighting also the cultivars influence. In BDC with starter, polyphenols amount doubled compared with commercial sample, while in TDB and CEL, phenolics remain almost unchanged. The main phenolics were hydroxytyrosol, tyrosol, verbascoside and luteolin, followed by hydroxytyrosol-acetate detected in BDC and cyanidine-3-glucoside and quercetin in CEL. Scavenger capacity in both DPPH and CAA assays, assessed the highest antioxidant effect for CEL with starters (21.7 mg Trolox eq/g FW; 8.5 μmol hydroxytyrosol eq/100 g FW). The polyphenols were highly in vitro bioaccessible (>60%), although modifications in their profile, probably for combined effect of environment and microorganisms, were noted. Finally, fermented table olives are excellent source of health promoting compounds, since hydroxytyrosol and tyrosol are almost 8 times more than in olive oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Olive leaf extracts protect cardiomyocytes against 4-hydroxynonenal-induced toxicity in vitro: comparison with oleuropein, hydroxytyrosol, and quercetin.

PubMed

Bali, Elif Burcu; Ergin, Volkan; Rackova, Lucia; Bayraktar, Oğuz; Küçükboyaci, Nurgün; Karasu, Çimen

2014-08-01

Olive (Olea europaea) leaf, an important traditional herbal medicine, displays cardioprotection that may be related to the cellular redox modulating effects of its polyphenolic constituents. This study was undertaken to investigate the protective effect of the ethanolic and methanolic extracts of olive leaves compared to the effects of oleuropein, hydroxytyrosol, and quercetin as a positive standard in a carbonyl compound (4-hydroxynonenal)-induced model of oxidative damage to rat cardiomyocytes (H9c2). Cell viability was detected by the MTT assay; reactive oxygen species production was assessed by the 2',7'-dichlorodihydrofluorescein diacetate method, and the mitochondrial membrane potential was determined using a JC-1 dye kit. Phospho-Hsp27 (Ser82), phospho-MAPKAPK-2 (Thr334), phospho-c-Jun (Ser73), cleaved-caspase-3 (cl-CASP3) (Asp175), and phospho-SAPK/JNK (Thr183/Tyr185) were measured by Western blotting. The ethanolic and methanolic extracts of olive leaves inhibited 4-hydroxynonenal-induced apoptosis, characterized by increased reactive oxygen species production, impaired viability (LD50: 25 µM), mitochondrial dysfunction, and activation of pro-apoptotic cl-CASP3. The ethanolic and methanolic extracts of olive leaves also inhibited 4-hydroxynonenal-induced phosphorylation of stress-activated transcription factors, and the effects of extracts on p-SAPK/JNK, p-Hsp27, and p-MAPKAPK-2 were found to be concentration-dependent and comparable with oleuropein, hydroxytyrosol, and quercetin. While the methanolic extract downregulated 4-hydroxynonenal-induced p-MAPKAPK-2 and p-c-Jun more than the ethanolic extract, it exerted a less inhibitory effect than the ethanolic extract on 4-hydroxynonenal-induced p-SAPK/JNK and p-Hsp27. cl-CASP3 and p-Hsp27 were attenuated, especially by quercetin. Experiments showed a predominant reactive oxygen species inhibitory and mitochondrial protecting ability at a concentration of 1-10 µg/mL of each extract, oleuropein, hydroxytyrosol, and quercetin. The ethanolic extract of olive leaves, which contains larger amounts of oleuropein, hydroxytyrosol, verbascoside, luteolin, and quercetin (by HPLC) than the methanolic one, has more protecting ability on cardiomyocyte viability than the methanolic extract or each phenolic compound against 4-hydroxynonenal-induced carbonyl stress and toxicity. Georg Thieme Verlag KG Stuttgart · New York.

Hydroxytyrosol and tyrosol esters partitioning into, location within, and effect on DOPC liposome bilayer behavior.

PubMed

Evans, Kervin O; Laszlo, Joseph A; Compton, David L

2015-05-01

The phenols hydroxytyrosol and tyrosol made abundantly available through olive oil processing were enzymatically transesterified into effective lipophilic antioxidants with cuphea oil. The hydroxytyrosyl and tyrosyl esters made from cuphea oil were assessed for their ability to partition into, locate within and effect the bilayer behavior of 1,2-dioloeoylphosphatidylcholine liposomes and compared to their counterparts made from decanoic acid. Partitioning into liposomes was on the same scale for both hydroxytyrosyl derivatives and both tyrosyl derivatives. All were found to locate nearly at the same depth within the bilayer. Each was found to affect bilayer behavior in a distinct manner. Published by Elsevier B.V.

Nutritionally relevant concentrations of resveratrol and hydroxytyrosol mitigate oxidative burst of human granulocytes and monocytes and the production of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages.

PubMed

Bigagli, Elisabetta; Cinci, Lorenzo; Paccosi, Sara; Parenti, Astrid; D'Ambrosio, Mario; Luceri, Cristina

2017-02-01

The health benefits of bio-active phenolic compounds have been largely investigated in vitro at concentrations which exceed those reachable in vivo. We investigated and compared the anti-inflammatory effects of resveratrol, hydroxytyrosol and oleuropein at physiologically relevant concentrations by using in vitro models of inflammation. Human granulocytes and monocytes were stimulated with phorbol myristate acetate (PMA) and the ability of resveratrol, hydroxytyrosol and oleuropein to inhibit the oxidative burst and CD11b expression was measured. Nitric oxide (NO), prostaglandin E2 (PGE2) levels, COX-2, iNOS, TNFα, IL-1β and miR-146a expression and activation of the transcription factor Nrf2 were evaluated in macrophages RAW 264.7 stimulated with LPS (1μg/ml) for 18h, exposed to resveratrol, hydroxytyrosol and oleuropein (5 and 10μM). Synergistic effects were explored as well, together with the levels of PGE2, COX-2 and IL-1β expression in macrophages after 6h of LPS stimulation. PGE2 and COX-2 expression were also assessed on human monocytes. All the tested compounds inhibited granulocytes oxidative burst in a concentration dependent manner and CD11b expression was also significantly counteracted by resveratrol and hydroxytyrosol. The measurement of oxidative burst in human monocytes produced similar effects being resveratrol more active. Hydroxytyrosol and resveratrol inhibited the production of NO and PGE2 but did not reduce iNOS, TNFα or IL-1β gene expression in LPS-stimulated RAW 264.7 for 18h. Resveratrol slightly decreased COX-2 expression after 18h but not after 6h, but reduced PGE2 levels after 6h. Resveratrol and hydroxytyrosol 10μM induced NRf2 nuclear translocation and reduced miR-146a expression in LPS treated RAW 264.7. Overall, we reported an anti-inflammatory effect of resveratrol and hydroxytyrosol at low, nutritionally relevant concentrations, involving the inhibition of granulocytes and monocytes activation, the modulation of miR-146a expression and the activation of Nrf2. A regular dietary intake of resveratrol and hydroxytyrosol may be a useful complementary strategy to control inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Partition behavior of virgin olive oil phenolic compounds in oil-brine mixtures during thermal processing for fish canning.

PubMed

Sacchi, Raffaele; Paduano, Antonello; Fiore, Francesca; Della Medaglia, Dorotea; Ambrosino, Maria Luisa; Medina, Isabel

2002-05-08

The chemical modifications and partitioning toward the brine phase (5% salt) of major phenol compounds of extra virgin olive oil (EVOO) were studied in a model system formed by sealed cans filled with oil-brine mixtures (5:1, v/v) simulating canned-in-oil food systems. Filled cans were processed in an industrial plant using two sterilization conditions commonly used during fish canning. The partitioning of phenolic compounds toward brine induced by thermal processing was studied by reversed-phase high-performance liquid chromatographic analysis of the phenol fraction extracted from oils and brine. Hydroxytyrosol (1), tyrosol (2), and the complex phenolic compounds containing 1 and 2 (i.e., the dialdehydic form of decarboxymethyl oleuropein aglycon 3, the dialdehydic form of decarboxymethyl ligstroside aglycon 4, and the oleuropein aglycon 6) decreased in the oily phase after sterilization with a marked partitioning toward the brine phase. The increase of the total amount of 1 and 2 after processing, as well as the presence of elenolic acid 7 released in brine, revealed the hydrolysis of the ester bond of hydrolyzable phenolic compounds 3, 4, and 6 during thermal processing. Both phenomena (partitioning toward the water phase and hydrolysis) contribute to explain the loss of phenolic compounds exhibited by EVOO used as filling medium in canned foods, as well as the protection of n-3 polyunsaturated fatty acids in canned-in-EVOO fish products.

Phenols and the antioxidant capacity of Mediterranean vegetables prepared with extra virgin olive oil using different domestic cooking techniques.

PubMed

Ramírez-Anaya, Jessica Del Pilar; Samaniego-Sánchez, Cristina; Castañeda-Saucedo, Ma Claudia; Villalón-Mir, Marina; de la Serrana, Herminia López-García

2015-12-01

Potato, tomato, eggplant and pumpkin were deep fried, sautéed and boiled in Mediterranean extra virgin olive oil (EVOO), water, and a water/oil mixture (W/O). We determined the contents of fat, moisture, total phenols (TPC) and eighteen phenolic compounds, as well as antioxidant capacity in the raw vegetables and compared these with contents measured after cooking. Deep frying and sautéing led to increased fat contents and TPC, whereas both types of boiling (in water and W/O) reduced the same. The presence of EVOO in cooking increased the phenolics identified in the raw foods as oleuropein, pinoresinol, hydroxytyrosol and tyrosol, and the contents of vegetable phenolics such as chlorogenic acid and rutin. All the cooking methods conserved or increased the antioxidant capacity measured by DPPH, FRAP and ABTS. Multivariate analyses showed that each cooked vegetable developed specific phenolic and antioxidant activity profiles resulting from the characteristics of the raw vegetables and the cooking techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of conventional heating on the stability of major olive oil phenolic compounds by tandem mass spectrometry and isotope dilution assay.

PubMed

Attya, Mohamed; Benabdelkamel, Hicham; Perri, Enzo; Russo, Anna; Sindona, Giovanni

2010-12-01

The quality of olive oils is sensorially tested by accurate and well established methods. It enables the classification of the pressed oils into the classes of extra virgin oil, virgin oil and lampant oil. Nonetheless, it would be convenient to have analytical methods for screening oils or supporting sensorial analysis using a reliable independent approach based on exploitation of mass spectrometric methodologies. A number of methods have been proposed to evaluate deficiencies of extra virgin olive oils resulting from inappropriate technological treatments, such as high or low temperature deodoration, and home cooking processes. The quality and nutraceutical value of extra virgin olive oil (EVOO) can be related to the antioxidant property of its phenolic compounds. Olive oil is a source of at least 30 phenolic compounds, such as oleuropein, oleocanthal, hydroxytyrosol, and tyrosol, all acting as strong antioxidants, radical scavengers and NSAI-like drugs. We now report the efficacy of MRM tandem mass spectrometry, assisted by the isotope dilution assay, in the evaluation of the thermal stability of selected active principles of extra virgin olive oil.

Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corona, Giulia; Dipartimento di Biologia Sperimentale, Sez. Patologia Sperimentale, Universita degli Studi di Cagliari, 09042 Monserrato; Deiana, Monica

2007-10-26

We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 {mu}g/ml) the number of cells in the G2/M phase increased to 51.82 {+-} 2.69% relative to control cells (15.1 {+-} 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 {mu}g/ml) to exert rapid inhibitionmore » of p38 (38.7 {+-} 4.7%) and CREB (28.6 {+-} 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 {+-} 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development.« less

Olive Component Oleuropein Promotes β-Cell Insulin Secretion and Protects β-Cells from Amylin Amyloid-Induced Cytotoxicity.

PubMed

Wu, Ling; Velander, Paul; Liu, Dongmin; Xu, Bin

2017-09-26

Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms for how it affects β-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in β-cells. The effect is dose-dependent and stimulates the ERK/MAPK signaling pathway. We further demonstrated that oleuropein inhibits the cytotoxicity induced by amylin amyloids, a hallmark feature of type 2 diabetes. We demonstrated that these dual functions are structure-specific: we identified the 3-hydroxytyrosol moiety of oleuropein as the main functional entity responsible for amyloid inhibition, but the novel GSIS function requires the entire structure scaffold of the molecule.

Rapid determination of hydrophilic phenols in olive oil by vortex-assisted reversed-phase dispersive liquid-liquid microextraction and screen-printed carbon electrodes.

PubMed

Fernández, Elena; Vidal, Lorena; Canals, Antonio

2018-05-01

A novel approach is presented to determine hydrophilic phenols in olive oil samples, employing vortex-assisted reversed-phase dispersive liquid-liquid microextraction (RP-DLLME) for sample preparation and screen-printed carbon electrodes for voltammetric analysis. The oxidation of oleuropein, hydroxytyrosol, caffeic acid, ferulic acid and tyrosol was investigated, being caffeic acid and tyrosol selected for quantification. A matrix-matching calibration using sunflower oil as analyte-free sample diluted with hexane was employed to compensate matrix effects. Samples were analyzed under optimized RP-DLLME conditions, i.e., extractant phase, 1M HCl; extractant volume, 100µL; extraction time, 2min; centrifugation time, 10min; centrifugation speed, 4000rpm. The working range showed a good linearity between 0.075 and 2.5mgL -1 (r = 0.998, N = 7) for caffeic acid, and between 0.075 and 3mgL -1 (r = 0.999, N = 8) for tyrosol. The methodological limit of detection was empirically established at 0.022mgL -1 for both analytes, which is significantly lower than average contents found in olive oil samples. The repeatability was evaluated at two different spiking levels (i.e., 0.5mgL -1 and 2mgL -1 ) and coefficients of variation ranged from 8% to 11% (n = 5). The applicability of the proposed method was tested in olive oil samples of different quality (i.e., refined olive oil, virgin olive oil and extra virgin olive oil). Relative recoveries varied between 83% and 108% showing negligible matrix effects. Finally, fifteen samples were analyzed by the proposed method and a high correlation with the traditional Folin-Ciocalteu spectrophotometric method was obtained. Thereafter, the concentrations of the fifteen oil samples were employed as input variables in linear discriminant analysis in order to distinguish between olive oils of different quality. Copyright © 2017 Elsevier B.V. All rights reserved.

Olive oil compounds inhibit vascular endothelial growth factor receptor-2 phosphorylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamy, Sylvie, E-mail: lamy.sylvie@uqam.ca; Ouanouki, Amira; Béliveau, Richard

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential ofmore » these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention. - Highlights: • We investigated five compounds contained in extra virgin olive oil on angiogenesis. • Hydroxytyrosol, taxifolin and oleic acid are the best angiogenesis inhibitors. • Olive oil compounds affect endothelial cell functions essential for angiogenesis. • Olive oil compounds inhibit specific autophosphorylation sites of VEGFR-2. • Hydroxytyrosol, taxifolin and oleic acid inhibit VEGFR-2 signaling pathway.« less

Determination of hydroxytyrosol and tyrosol by liquid chromatography for the quality control of cosmetic products based on olive extracts.

PubMed

Miralles, Pablo; Chisvert, Alberto; Salvador, Amparo

2015-01-01

An analytical method for the simultaneous determination of hydroxytyrosol and tyrosol in different types of olive extract raw materials and cosmetic cream samples has been developed. The determination was performed by liquid chromatography with UV spectrophotometric detection. Different chromatographic parameters, such as mobile phase pH and composition, oven temperature and different sample preparation variables were studied. The best chromatographic separation was obtained under the following conditions: C18 column set at 35°C and isocratic elution of a mixture ethanol: 1% acetic acid solution at pH 5 (5:95, v/v) as mobile phase pumped at 1 mL min(-1). The detection wavelength was set at 280 nm and the total run time required for the chromatographic analysis was 10 min, except for cosmetic cream samples where 20 min runtime was required (including a cleaning step). The method was satisfactorily applied to 23 samples including solid, water-soluble and fat-soluble olive extracts and cosmetic cream samples containing hydroxytyrosol and tyrosol. Good recoveries (95-107%) and repeatability (1.1-3.6%) were obtained, besides of limits of detection values below the μg mL(-1) level. These good analytical features, as well as its environmentally-friendly characteristics, make the presented method suitable to carry out both the control of the whole manufacture process of raw materials containing the target analytes and the quality control of the finished cosmetic products. Copyright © 2014 Elsevier B.V. All rights reserved.

Microchip electrophoresis with amperometric detection for a novel determination of phenolic compounds in olive oil.

PubMed

Godoy-Caballero, María del Pilar; Acedo-Valenzuela, María Isabel; Galeano-Díaz, Teresa; Costa-García, Agustín; Fernández-Abedul, María Teresa

2012-11-07

The relevance of the development of microchip electrophoresis applications in the field of food analysis is considered in this work. A novel method to determine important phenolic compounds in extra virgin olive oil samples using a miniaturized chemical analysis system is presented in this paper. Three interesting phenolic compounds in olive oil and fruit (tyrosol, hydroxytyrosol and oleuropein glucoside) were studied by end-channel amperometric detection using a 100 μm gold wire as working electrode in glass microchip electrophoresis. The electrochemical behavior of these compounds was studied and the medium to carry out their detection was selected (0.1 M aqueous sulfuric acid). The best conditions for the separation were achieved in sodium tetraborate (10% methanol, pH 9.50) with different concentrations for the sample and the running buffer in order to allow the sample stacking phenomenon. The injection was carried out using 600 V for 3 s and the separation voltage was set at 1000 V. The quality of the method was evaluated through its analytical figures of merit and by its performance on real extra virgin olive oil samples. Determination of these compounds was carried out using the standard addition calibration method with good recoveries.

Oleuropein in Olive and its Pharmacological Effects

PubMed Central

Omar, Syed Haris

2010-01-01

Olive from Olea europaea is native to the Mediterranean region and, both the oil and the fruit are some of the main components of the Mediterranean diet. The main active constituents of olive oil include oleic acid, phenolic constituents, and squalene. The main phenolic compounds, hydroxytyrosol and oleuropein, give extra-virgin olive oil its bitter, pungent taste. The present review focuses on recent works that have analyzed the relationship between the major phenolic compound oleuropein and its pharmacological activities including antioxidant, anti-inflammatory, anti-atherogenic, anti-cancer activities, antimicrobial activity, antiviral activity, hypolipidemic and hypoglycemic effect. PMID:21179340

Antioxidant/prooxidant effects of dietary non-flavonoid phenols on the Cu2+-induced oxidation of human low-density lipoprotein (LDL).

PubMed

Briante, Raffaella; Febbraio, Ferdinando; Nucci, Roberto

2004-11-01

A central role in the oxidative development of atherosclerotic lesions has been ascribed to the peroxidation of plasma low-density lipoprotein (LDL). Dietary supplementation with virgin olive oils increases the total plasma antioxidant status and the resistance of low-density lipoprotein to ex vivo oxidation. We have studied the effects of some dietary non-flavonoid phenols from Olea europaea L., both in purified form or in complex mixtures obtained by biotransformation of olive leaf extracts, on the LDL oxidation induced by Cu2+ ions. Cu2+-Induced LDL oxidation is inhibited by oleuropein and hydroxytyrosol in the initiation phase of the reaction at concentrations of phenols higher than that of Cu2+ ions. Interestingly, at lower concentration, both phenols anticipated the initiation process of LDL oxidation, thus exerting prooxidant capacities. Although similar effects are already described for flavonoids, such as quercetin, rutin, and apigenin, it is the first time that a prooxidant effect of dietary non-flavonoid phenols, such as oleuropein and hydroxytyrosol, on the LDL oxidation is reported. Our results show that a net effect of oleuropein and hydroxytyrosol on Cu2+-induced LDL peroxidation is determined by a balance of their pro- and antioxidant capacities. It is worth to underline that, during Cu2+-induced LDL oxidation in the presence of bioreactor eluates, we have evidence of a synergistic effect among phenolic compounds that enhance their antioxidant capacities so avoiding the prooxidant effects.

Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.

PubMed

Mahmoudi, Asma; Ghorbel, Hèla; Feki, Ines; Bouallagui, Zouhaier; Guermazi, Fadhel; Ayadi, Lobna; Sayadi, Sami

2018-04-27

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Valorization of Oleuropein Via Tunable Acid-Promoted Methanolysis.

PubMed

Afonso, Carlos; Cavaca, Lidia A S; Rodrigues, Catarina A B; Simeonov, Svilen P; Gomes, Rafael F A; Coelho, Jaime A S; Romanelli, Gustavo P; Sathicq, Angel G; Martínez, José J

2018-05-28

The acid-promoted methanolysis of Oleuropein was studied using a variety of homogeneous and heterogeneous acid catalysts. Exclusive cleavage of the acetal bond between the glucoside and the monoterpene subunits or further hydrolysis of the hydroxytyrosol ester and subsequent intramolecular rearrangement were observed upon identification of the most efficient catalyst and experimental conditions. Furthermore, selected conditions were tested using Oleuropein under continuous flow and using a crude mixture extracted from olive leaves under batch. Formation of (-) methyl elenolate was also observed in this study, which is a reported precursor for the synthesis of the antihypertensive drug (-) ajmalicine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenol esterase activity of porcine skin

USDA-ARS?s Scientific Manuscript database

The alkyl esters of plant-derived phenols may serve as slow-release sources for cutaneous delivery of antioxidants. The ability of skin esterases to hydrolyze phenolic esters was examined. Esters of tyrosol and hydroxytyrosol were prepared from decanoic and lipoic acids. Ferulic acid was esterified ...

Factors influencing the formation of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine: Temperature, alcoholic degree, and amino acids concentration.

PubMed

Bordiga, M; Lorenzo, C; Pardo, F; Salinas, M R; Travaglia, F; Arlorio, M; Coïsson, J D; Garde-Cerdán, T

2016-04-15

The validation of a HPLC-PDA-MS/MS chromatographic method for the quali/quantitative characterization of histaminol, hydroxytyrosol, tyrosol, and tryptophol in wine has been described and discussed. Four standards showed a good linearity with high correlation coefficient values (over 0.9989) and LOD and LOQ were 0.001-0.015 mg/L and 0.004-0.045 mg/L, respectively. Furthermore, this study reported how factors such as temperature, alcoholic degree, and amino acids concentration are able to influence the formation of these four alcohols in Monastrell wines. The quantification values of these alcohols has been detected both at the half and end of alcoholic fermentation, and at the end of malolactic fermentation. In relation to interactions between factors, several significant variations emerged (p ⩽ 0.001). The impact of amino acids supplementation in Monastrell must it has been demonstrated, mainly in regards to histaminol and tryptophol. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessment of Olea europaea L. fruit extracts: Phytochemical characterization and anticancer pathway investigation.

PubMed

Maalej, Amina; Bouallagui, Zouhaier; Hadrich, Fatma; Isoda, Hiroko; Sayadi, Sami

2017-06-01

Olea europaea L. has been widely used as an advantageous rich source of bioactive compounds of high economic value leading to its use in pharmaceutical, cosmetic, and agriculture industries. Ethanolic extracts of olive fruits from three different cultivars (OFE) were studied for their phytochemical contents and were investigated for antioxidant activities and anticancer potential. Major polyphenols detected in these extracts were tyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigenin. All these compounds have shown to significantly contribute to the antioxidant activity of OFE, which was evaluated by DPPH and ABTS assays. Proliferation of hepatic and colon cancer cells, HepG2 and Caco-2, were shown to be sensitive to OFE with IC 50 less than 1.6mg/ml for all tested extracts. Moreover, flow cytometry analysis showed that OFE induced cell cycle arrest in the S-phase within both HepG2 and Caco-2 cells. This has triggered a cell death mechanism as shown by DNA fragmentation, expression of p53 and phosphorylation level of Akt and Erk proteins. Interestingly, these extracts could be further used as a potential source of natural compounds with both antioxidant and anticancer effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Improving in vivo conversion of oleuropein into hydroxytyrosol by oral granules containing probiotic Lactobacillus plantarum 299v and an Olea europaea standardized extract.

PubMed

Aponte, Maria; Ungaro, Francesca; d'Angelo, Ivana; De Caro, Carmen; Russo, Roberto; Blaiotta, Giuseppe; Dal Piaz, Fabrizio; Calignano, Antonio; Miro, Agnese

2018-05-30

This study reports novel food-grade granules for co-delivery of L. plantarum 299v and a standardized extract of Olea europaea leaves (Phenolea®) as oral carrier of probiotics and hydroxytyrosol. Different granule formulations containing either L. plantarum 299v (Lac), or the olive leave extract (Phe) or their combination (Lac-Phe) have been successfully produced through wet granulation employing excipients generally regarded as safe as granulating/binding agents. L. plantarum cells withstood the manufacturing process and were stable upon storage at 4 °C for more than 6 months. In vitro dissolution studies in simulated gastro-intestinal fluids showed the capability of the granules to rapidly dissolve and deliver both olive leave phenols and living L. plantarum cells. In simulated digestion conditions, Lac and Lac-Phe granules protected L. plantarum against the harsh environment of the gastro-intestinal tract. Co-administration of Lac and Phe oral granules to healthy mice provided for higher amounts of hydroxytyrosol in urines as compared to Phe granules alone, suggesting that L. plantarum 299v boosted in vivo conversion of oleuropein to hydroxytyrosol. On the other hand, PCR-assisted profiling of the Lactobacillus population in faeces obtained from mice treated with Lac or Lac plus Phe confirmed that the probiotic arrived alive to colon and was there able to exert a sort of perturbing effect on the climax colonic microflora. Overall, these results pave the way towards the development of a nutraceutical useful for combined delivery of bioactive hydroxytyrosol and probiotics to colon site. Copyright © 2018 Elsevier B.V. All rights reserved.

Hydrolysis of Oleuropein by Lactobacillus plantarum Strains Associated with Olive Fermentation.

PubMed

Ciafardini, G; Marsilio, V; Lanza, B; Pozzi, N

1994-11-01

Oleuropein (Chemical Abstracts Service registry number 32619-42-4), a bitter-tasting secoiridoid glucoside commonly found in leaves of the olive tree as well as in olives (Olea europaea L.), was found to be hydrolyzed by the beta-glucosidase (EC 3.2.1.2.1) produced by oleuropeinolytic Lactobacillus plantarum-type strains. Three strains, designated B17, B20, and B21, were isolated from the brine of naturally ripe olives not treated with alkali. These strains were rod-shaped forms, grown at a pH 3.5 limit, and tolerated 1% oleuropein and 8% NaCl in the growth medium. The beta-glucosidase produced hydrolyzed 5-bromo-4-chloro-3-indolyl-beta-d-glucopy-ranoside as well as oleuropein. The presence of 2% glucose in the medium inhibited activity by 40 to 50%, depending on the bacterial strain. Chromatographic analysis of the trimethylsilyl derivatives of the products obtained after 7 days of incubation at 30 degrees C of strain B21 showed all the hydrolysis products of oleuropein, i.e., aglycone, iridoid monoterpen, and 3,4-dihydroxyphenylethanol (hydroxytyrosol). Oleuropein and its aglycone after 21 days of incubation decreased to trace levels with the simultaneous increase in concentration of beta-3,4-dihydroxyphenylethanol.

In vitro inhibitory effects of plant-derived by-products against Cryptosporidium parvum

PubMed Central

Teichmann, Klaus; Kuliberda, Maxime; Schatzmayr, Gerd; Pacher, Thomas; Zitterl-Eglseer, Karin; Joachim, Anja; Hadacek, Franz

2016-01-01

Disposal of organic plant wastes and by-products from the food or pharmaceutical industries usually involves high costs. In the present study, 42 samples derived from such by-products were screened in vitro against Cryptosporidium parvum, a protozoan parasite that may contaminate drinking water and cause diarrhoea. The novel bioassay was previously established in the microtitre plate format. Human ileocaecal adenocarcinoma (HCT-8) cell cultures were seeded with C. parvum oocysts and parasite development was monitored by an indirect fluorescent antibody technique (IFAT) and microscopic assessment for clusters of secondary infection (CSI). Minimum inhibitory concentrations (MICs) and potential detrimental effects on the host cells were determined. An ethanolic extract from olive (Olea europaea) pomace, after oil pressing and phenol recovery, reproducibly inhibited C. parvum development (MIC = 250–500 μg mL−1, IC50 = 361 (279–438) μg mL−1, IC90 = 467 (398–615) μg mL−1). Accordingly, tyrosol, hydroxytyrosol, trans-coniferyl alcohol and oleuropein were selected as reference test compounds, but their contributions to the observed activity of the olive pomace extract were insignificant. The established test system proved to be a fast and efficient assay for identifying anti-cryptosporidial activities in biological waste material and comparison with selected reference compounds. PMID:27627637

Hydrolysis of Oleuropein by Lactobacillus plantarum Strains Associated with Olive Fermentation

PubMed Central

Ciafardini, G.; Marsilio, V.; Lanza, B.; Pozzi, N.

1994-01-01

Oleuropein (Chemical Abstracts Service registry number 32619-42-4), a bitter-tasting secoiridoid glucoside commonly found in leaves of the olive tree as well as in olives (Olea europaea L.), was found to be hydrolyzed by the β-glucosidase (EC 3.2.1.2.1) produced by oleuropeinolytic Lactobacillus plantarum-type strains. Three strains, designated B17, B20, and B21, were isolated from the brine of naturally ripe olives not treated with alkali. These strains were rod-shaped forms, grown at a pH 3.5 limit, and tolerated 1% oleuropein and 8% NaCl in the growth medium. The β-glucosidase produced hydrolyzed 5-bromo-4-chloro-3-indolyl-β-d-glucopy-ranoside as well as oleuropein. The presence of 2% glucose in the medium inhibited activity by 40 to 50%, depending on the bacterial strain. Chromatographic analysis of the trimethylsilyl derivatives of the products obtained after 7 days of incubation at 30°C of strain B21 showed all the hydrolysis products of oleuropein, i.e., aglycone, iridoid monoterpen, and 3,4-dihydroxyphenylethanol (hydroxytyrosol). Oleuropein and its aglycone after 21 days of incubation decreased to trace levels with the simultaneous increase in concentration of β-3,4-dihydroxyphenylethanol. Images PMID:16349442

Bioenergetic strategy of microalgae for the biodegradation of tyrosol and hydroxytyrosol.

PubMed

Papazi, Aikaterini; Ioannou, Andreas; Symeonidi, Myrto; Doulis, Andreas G; Kotzabasis, Kiriakos

2017-05-01

Olive mill wastewater has significant polluting properties due to its high phenolic content [mainly tyrosol (trs) and hydroxytyrosol (htrs)]. Growth kinetics and a series of fluorescence induction measurements for Scenedesmus obliquus cultures showed that microalgae can be tolerant of these phenolic compounds. Changes in the cellular energy reserves and concentration of the phenolic compounds adjust the "toxicity" of these compounds to the microalgae and are, therefore, the main parameters that affect biodegradation. Autotrophic growth conditions of microalgae and high concentrations of trs or htrs induce higher biodegradation compared with mixotrophic conditions and lower phenolic concentrations. When microalgae face trs and htrs simultaneously, biodegradation begins from htrs, the more energetically demanding compound. All these lead to the conviction that microalgae have a "rational" management of cellular energy balance. Low toxicity levels lead to higher growth and lower biodegradation, whereas higher toxicity levels lead to lower growth and higher biodegradation. The selection of appropriate conditions (compatible to the bioenergetic strategies of microalgae) seems to be the key for a successful biodegradation of a series of toxic compounds, thus paving the way for future biotechnological applications for solving complicated pollution problems, like the detoxification of olive mill wastewater.

Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives.

PubMed

Fernandez-Pastor, Ignacio; Fernandez-Hernandez, Antonia; Rivas, Francisco; Martinez, Antonio; Garcia-Granados, Andres; Parra, Andres

2016-07-22

Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.

Oleuropein and hydroxytyrosol activate GPER/ GPR30-dependent pathways leading to apoptosis of ER-negative SKBR3 breast cancer cells.

PubMed

Chimento, Adele; Casaburi, Ivan; Rosano, Camillo; Avena, Paola; De Luca, Arianna; Campana, Carmela; Martire, Emilia; Santolla, Maria Francesca; Maggiolini, Marcello; Pezzi, Vincenzo; Sirianni, Rosa

2014-03-01

We have previously demonstrated that oleuropein (OL) and hydroxytyrosol (HT) reduce 17β-estradiol-mediated proliferation in MCF-7 breast cancer (BC) cells without affecting the classical genomic action of estrogen receptor (ER), but activating instead the ERK1/2 pathway. Here, we hypothesized that this inhibition could be mediated by a G-protein-coupled receptor named GPER/GPR30. Using the ER-negative and GPER-positive SKBR3 BC cells as experimental model, we investigated the effects of OL and HT on GPER-mediated activation of downstream pathways. Docking simulations and ligand-binding studies evidenced that OL and HT are able to bind GPER. MTT cell proliferation assays revealed that both phenols reduced SKBR3 cell growth; this effect was abolished silencing GPER. Focusing on OL and HT GPER-mediated pathways, using Western blot analysis we showed a sustained ERK1/2 activation triggering an intrinsic apoptotic pathway. Showing that OL and HT work as GPER inverse agonists in ER-negative and GPER-positive SKBR3 BC cells, we provide novel insights into the potential of these two molecules as tools in the therapy of this subtype of BC. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Energetic and Structural Properties of Two Phenolic Antioxidants: Tyrosol and Hydroxytyrosol.

PubMed

Dávalos, Juan Z; Valderrama-Negrón, Ana C; Barrios, Julio R; Freitas, Vera L S; Ribeiro da Silva, Maria D M C

2018-04-26

Theoretical and experimental studies on the energetic, structural and some other relevant physicochemical properties of the antioxidant tyrosol (1), hydroxytyrosol (1OH) molecules and the corresponding radicals 1 rad • and 1O rad • are reported in this work. The experimental values of the gas-phase enthalpy of formation, Δ f H m 0 (g), in kJ·mol -1 , of 1 (-302.4 ± 3.4) and 1OH (-486.3 ± 4.1) have been determined. Quantum chemical calculations, at DFT (M05-2X) and composite ab initio G3 and G4 levels of theory, provided results that served to (i) confirm the excellent consistency of the experimental measurements performed, (ii) establish that the stabilizing effect of H-bond of hydroxyethyl chain and aromatic ring (OH···π interaction) is smaller in radicals than in parent molecules, (iii) deduce-combining experimental data in isodesmic reactions-Δ f H m 0 (g) of radicals 1 rad • (-152.3 ± 4.4 kJ·mol -1 ) and 1O rad • (-370.6 ± 3.8 kJ·mol -1 ), (iv) estimate a reliable O-H bond dissociation enthalpy, BDE of 1 (368.1 ± 5.6 kJ·mol -1 ) and of 1OH (333.7 ± 5.6 kJ·mol -1 ), and (v) corroborate-using "BDE criteria"-than 1OH is a more effective antioxidant than 1.

Kinetic study of hydroxytyrosol oxidation and its related compounds by Red Globe grape polyphenol oxidase.

PubMed

García-García, María Inmaculada; Hernández-García, Samanta; Sánchez-Ferrer, Álvaro; García-Carmona, Francisco

2013-06-26

Red Globe grape polyphenol oxidase, partially purified using phase partitioning with Triton-X114, was used to study the oxidation of hydroxytytosol (HT) and its related compounds tyrosol (TS), tyrosol acetate (TSA), and hydroxytyrosol acetate (HTA). The enzyme showed activity toward both monophenols (monophenolase activity) and o-diphenols (diphenolase activity) with a pH optimum (pH 6.5) that was independent of the phenol used. However, the optimal temperature for diphenolase activity was substrate-dependent, with a broad optimum of 25-65 °C for HT, compared with the maximum obtained for HTA (40 °C). Monophenolase activity showed the typical lag period, which was modulated by pH, substrate and enzyme concentrations, and the presence of catalytic amounts of o-diphenols. When the catalytic power (Vmax/K(M)) was determined for both activities, higher values were observed for o-diphenols than for monophenols: 9-fold higher for the HT/TS pair and 4-fold higher for HTA/TSA pair. Surprisingly, this ratio was equally higher for TSA (2.2-fold) compared with that of TS, whereas no such effect was observed for o-diphenols. This higher efficiency of TSA could be related to its greater hydrophobicity. Acetyl modification of these phenols not only changes the kinetic parameters of the enzyme but also affects their antioxidant activity (ORAC-FL assays), which is lower in HTA than in HT.

Olive oil phenolics are dose-dependently absorbed in humans.

PubMed

Visioli, F; Galli, C; Bornet, F; Mattei, A; Patelli, R; Galli, G; Caruso, D

2000-02-25

Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.

Biological effects of the olive polyphenol, hydroxytyrosol: An extra view from genome-wide transcriptome analysis.

PubMed

Nan, Jia Nancy; Ververis, Katherine; Bollu, Sameera; Rodd, Annabelle L; Swarup, Oshi; Karagiannis, Tom C

2014-01-01

Epidemiological and clinical studies have established the health benefits of the Mediterranean diet, an important component of which are olives and olive oil derived from the olive tree (Olea Europea). It is now well-established that not only the major fatty acid constituents, but also the minor phenolic components, in olives and olive oil have important health benefits. Emerging research over the past decade has highlighted the beneficial effects of a range of phenolic compounds from olives and olive oil, particularly for cardiovascular diseases, metabolic syndrome and inflammatory conditions. Mechanisms of action include potent antioxidant and anti-inflammatory effects. Further, accumulating evidence indicates the potential of the polyphenols and potent antioxidants, hydroxytyrosol and oleuropein in oncology. Numerous studies, both in vitro and in vivo, have demonstrated the anticancer effects of hydroxytyrosol which include chemopreventive and cell-specific cytotoxic and apoptotic effects. Indeed, the precise molecular mechanisms accounting for the antioxidant, anti-inflammatory and anticancer properties are now becoming clear and this is, at least in part, due to high through-put gene transcription profiling. Initially, we constructed phylogenetic trees to visualize the evolutionary relationship of members of the Oleaceae family and secondly, between plants producing hydroxytyrosol to make inferences of potential similarities or differences in their medicinal properties and to identify novel plant candidates for the treatment and prevention of disease. Furthermore, given the recent interest in hydroxytyrosol as a potential anticancer agent and chemopreventative we utilized transcriptome analysis in the erythroleukemic cell line K562, to investigate the effects of hydroxytyrosol on three gene pathways: the complement system, The Warburg effect and chromatin remodeling to ascertain relevant gene candidates in the prevention of cancer.

Simple and efficient sustainable semi-synthesis of oleacein [2-(3,4-hydroxyphenyl) ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] as potential additive for edible oils.

PubMed

Costanzo, Paola; Bonacci, Sonia; Cariati, Luca; Nardi, Monica; Oliverio, Manuela; Procopio, Antonio

2018-04-15

A simple and very environmental friendly microwave assisted method to produce oleacein in good yield starting from the easily available oleuropein is here presented. The methodology is proposed to produce the appropriate amount of hydroxytyrosol derivatives to enrich a commercial oil for an oil which provides beneficial effects on the human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reuse of drinking water treatment sludge for olive oil mill wastewater treatment.

PubMed

Fragoso, R A; Duarte, E A

2012-01-01

Olive mill wastewater (OMW) results from the production of olive oil, which is an important traditional agro-industry in Mediterranean countries. In continuous three-phase centrifugation 1.0-1.2 m(3) of OMW are produced per ton of processed olives. Discharge of OMW is of serious environmental concern due to its high content of organic matter with phytotoxic properties, namely phenolic compounds. Meanwhile, drinking water treatment sludge (DWTS) is produced in high amounts and has long been considered as a waste for landfill. The aim of this work was the assessment of reusing DWTS for OMW treatment. High performance liquid chromatography (HPLC) analysis was carried out to determine the phenolic compounds present and to evaluate if they are recalcitrant. Treatability assays were performed using a dosage of DWTS from 50 to 300 g L(-1). Treatment efficiency was evaluated based on the removal of chemical oxygen demand (COD), biochemical oxygen demand (BOD), total solids (TS), total suspended solids (TSS), total volatile solids (TVS), oil and grease (OG), phenols (total phosphorous (TP) and HPLC fraction). Results from OMW HPLC characterization identified a total of 13 compounds; the major ones were hydroxytyrosol, tyrosol, caffeic acid, p-cumaric acid and oleuropein. Treatability assays led to a maximum reduction of about 90% of some of the phenolic compounds determined by HPLC. Addition of 200-300 g L(-1) of DWTS reduced 40-50% of COD, 45-50% of TP, a maximum of nearly 70% TSS and 45% for TS and TVS. The OG fraction showed a reduction of about 90%, achieved adding 300 g L(-1) od DWTS. This study points out the possibility of establishing an integrated management of OMW and DWTS, contributing to a decrease in the environmental impact of two industrial activities, olive oil production and drinking water treatment.

Olive phenolic compounds: metabolic and transcriptional profiling during fruit development

PubMed Central

2012-01-01

Background Olive (Olea europaea L.) fruits contain numerous secondary metabolites, primarily phenolics, terpenes and sterols, some of which are particularly interesting for their nutraceutical properties. This study will attempt to provide further insight into the profile of olive phenolic compounds during fruit development and to identify the major genetic determinants of phenolic metabolism. Results The concentration of the major phenolic compounds, such as oleuropein, demethyloleuropein, 3–4 DHPEA-EDA, ligstroside, tyrosol, hydroxytyrosol, verbascoside and lignans, were measured in the developing fruits of 12 olive cultivars. The content of these compounds varied significantly among the cultivars and decreased during fruit development and maturation, with some compounds showing specificity for certain cultivars. Thirty-five olive transcripts homologous to genes involved in the pathways of the main secondary metabolites were identified from the massive sequencing data of the olive fruit transcriptome or from cDNA-AFLP analysis. Their mRNA levels were determined using RT-qPCR analysis on fruits of high- and low-phenolic varieties (Coratina and Dolce d’Andria, respectively) during three different fruit developmental stages. A strong correlation was observed between phenolic compound concentrations and transcripts putatively involved in their biosynthesis, suggesting a transcriptional regulation of the corresponding pathways. OeDXS, OeGES, OeGE10H and OeADH, encoding putative 1-deoxy-D-xylulose-5-P synthase, geraniol synthase, geraniol 10-hydroxylase and arogenate dehydrogenase, respectively, were almost exclusively present at 45 days after flowering (DAF), suggesting that these compounds might play a key role in regulating secoiridoid accumulation during fruit development. Conclusions Metabolic and transcriptional profiling led to the identification of some major players putatively involved in biosynthesis of secondary compounds in the olive tree. Our data represent the first step towards the functional characterisation of important genes for the determination of olive fruit quality. PMID:22963618

Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

PubMed Central

Menicacci, Beatrice; Cipriani, Caterina; Margheri, Francesca

2017-01-01

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols. PMID:29084133

Optimization of parameters affecting signal intensity in an LTQ-orbitrap in negative ion mode: A design of experiments approach.

PubMed

Lemonakis, Nikolaos; Skaltsounis, Alexios-Leandros; Tsarbopoulos, Anthony; Gikas, Evagelos

2016-01-15

A multistage optimization of all the parameters affecting detection/response in an LTQ-orbitrap analyzer was performed, using a design of experiments methodology. The signal intensity, a critical issue for mass analysis, was investigated and the optimization process was completed in three successive steps, taking into account the three main regions of an orbitrap, the ion generation, the ion transmission and the ion detection regions. Oleuropein and hydroxytyrosol were selected as the model compounds. Overall, applying this methodology the sensitivity was increased more than 24%, the resolution more than 6.5%, whereas the elapsed scan time was reduced nearly to its half. A high-resolution LTQ Orbitrap Discovery mass spectrometer was used for the determination of the analytes of interest. Thus, oleuropein and hydroxytyrosol were infused via the instruments syringe pump and they were analyzed employing electrospray ionization (ESI) in the negative high-resolution full-scan ion mode. The parameters of the three main regions of the LTQ-orbitrap were independently optimized in terms of maximum sensitivity. In this context, factorial design, response surface model and Plackett-Burman experiments were performed and analysis of variance was carried out to evaluate the validity of the statistical model and to determine the most significant parameters for signal intensity. The optimum MS conditions for each analyte were summarized and the method optimum condition was achieved by maximizing the desirability function. Our observation showed good agreement between the predicted optimum response and the responses collected at the predicted optimum conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of sampling parameters on the radical scavenging potential of olive (Olea europaea L.) leaves.

PubMed

Papoti, Vassiliki T; Tsimidou, Maria Z

2009-05-13

The impact of sampling parameters, that is, cultivar, leaf age, and sampling date, on the radical scavenging potential of olive leaf extracts was examined via the DPPH(*) and other assays. Total phenol content was estimated colorimetrically and by fluorometry, whereas phenol composition was assessed by RP-HPLC coupled with diode array, fluorometric, and MS detection systems. Oleuropein was not always the major leaf constituent. Considerable differences noted in individual phenol levels (hydroxytyrosol, oleuropein and other secoiridoids, verbascoside, and flavonoids) among samples were not reflected either in the total phenol content or in the radical scavenging potential of the extracts. It can be suggested that olive leaf is a robust source of radical scavengers throughout the year and that differentiation in the levels of individual components depends rather on sampling period than on cultivar or age. The latter does not present predictable regularity. Exploitation of all types of leaves expected in an olive tree shoot for the extraction of bioactive compounds is feasible.

Effect of water deficit on leaf phenolic composition, gas exchange, oxidative damage and antioxidant activity of four Greek olive (Olea europaea L.) cultivars.

PubMed

Petridis, Antonios; Therios, Ioannis; Samouris, Georgios; Koundouras, Stefanos; Giannakoula, Anastasia

2012-11-01

The olive tree (Olea europaea L.) is often exposed to severe water stress during the summer season. In this study, we determined the changes in total phenol content, oleuropein and hydroxytyrosol in the leaves of four olive cultivars ('Gaidourelia', 'Kalamon', 'Koroneiki' and 'Megaritiki') grown under water deficit conditions for two months. Furthermore, we investigated the photosynthetic performance in terms of gas exchange and chlorophyll a fluorescence, as well as malondialdehyde content and antioxidant activity. One-year-old self-rooted plants were subjected to three irrigation treatments that received a water amount equivalent to 100% (Control, C), 66% (Field Capacity 66%, FC(66)) and 33% (Field Capacity 33%, FC(33)) of field capacity. Measurements were conducted 30 and 60 days after the initiation of the experiment. Net CO(2) assimilation rate, stomatal conductance and F(v)/F(m) ratio decreased only in FC(33) plants. Photosynthetic rate was reduced mainly due to stomatal closure, but damage to PSII also contributed to this decrease. Water stress induced the accumulation of phenolic compounds, especially oleuropein, suggesting their role as antioxidants. Total phenol content increased in FC(33) treatment and oleuropein presented a slight increase in FC(66) and a sharper one in FC(33) treatment. Hydroxytyrosol showed a gradual decrease as water stress progressed. Malondialdehyde (MDA) content increased due to water stress, mostly after 60 days, while antioxidant activity increased for all cultivars in the FC(33) treatment. 'Gaidourelia' could be considered as the most tolerant among the tested cultivars, showing higher phenolic concentration and antioxidant activity and lower lipid peroxidation and photochemical damage after two months of water stress. The results indicated that water stress affected olive tree physiological and biochemical parameters and magnitude of this effect depended on genotype, the degree of water limitation and duration of treatment. However, the severity as well as the duration of water stress might exceed antioxidant capacity, since MDA levels and subsequent oxidative damage increased after two months of water deficit. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain.

PubMed

Muscoli, C; Lauro, F; Dagostino, C; D'Agostino, C; Ilari, S; Giancotti, L A; Gliozzi, M; Costa, N; Carresi, C; Musolino, V; Casale, F; Ventrice, D; Oliverio, M; Oliverio, E; Palma, E; Nisticò, S; Nistico', S; Procopio, A; Rizzo, M; Mollace, V

2014-01-01

Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.

Effect of the composition of extra virgin olive oils on the differentiation and antioxidant capacities of twelve monovarietals.

PubMed

Fuentes, Edwar; Paucar, Fiorela; Tapia, Francisco; Ortiz, Jaime; Jimenez, Paula; Romero, Nalda

2018-03-15

The effect of the composition of twelve varieties of extra virgin olive oils (EVOOs) on their differentiation based in agronomic criteria and on the antioxidant capacity was studied. Principal component analysis permitted an overview of the samples and their compositions, showing evidence of grouping and correlation between antioxidant capacity, oleuropein and ligstroside derivatives (OLD) and specific extinction at 270. Oleic and linoleic acids, 3,4-DHPEA-EA and p-HPEA-EDA (OLD), unsaturated/saturated ratio and induction time (IT) allowed the correct classification of samples according to year of harvest, ripening stage and variety. The antioxidant capacity of EVOOs was satisfactory predicted through a partial least square model based on ΔK, hydroxytyrosol, pinoresinol, oleuropein derivate and IT. Validation of the model gave a correlation R>0.83 and an error of 7% for independent samples. This model could be a useful tool for the olive industry to highlight the nutritional quality of EVOOs and improve their marketing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioactivity Improvement of Olea europaea Leaf Extract Biotransformed by Wickerhamomyces anomalus Enzymes.

PubMed

Palmeri, Rosa; Restuccia, Cristina; Monteleone, Julieta Ines; Sperlinga, Elisa; Siracusa, Laura; Serafini, Mauro; Finamore, Alberto; Spagna, Giovanni

2017-06-01

Olive leaves represent a quantitatively significant by-product of agroindustry. They are rich in phenols, mainly oleuropein, which can be hydrolyzed into several bioactive compounds, including hydroxytyrosol. In this study, water extract from olive leaves 'Biancolilla' was analyzed for polyphenol profile, DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity and protective effect on differentiated Caco-2 cells. The efficacy of two enzymatic treatments in promoting the release of bioactive phenols was investigated: a) enzymatic extract from Wickerhamomyces anomalus, characterized by β-glucosidase and esterase activities; b) commercial β-glucosidase. Composition and bioactivity of the resulting extracts were compared. The results showed that the yeast-treated extract presented hydroxytyrosol content and DPPH radical scavenging activity comparable to those obtained using commercial β-glucosidase; however, it was showed the additional presence of hydroxycinnamic acids. In experiments on Caco-2 cells, the leaf extracts promoted the recovery of cell membrane barrier at different minimum effective concentrations. The high specificity of W. anomalus enzymatic extract may represent an effective tool for the release of bioactive phenols from olive by-products.

Role of the catechol group in the antioxidant and neuroprotective effects of virgin olive oil components in rat brain.

PubMed

De La Cruz, J P; Ruiz-Moreno, M I; Guerrero, A; López-Villodres, J A; Reyes, J J; Espartero, J L; Labajos, M T; González-Correa, J A

2015-05-01

The aim of the present study was to determine the role of the catechol group in the antioxidant and neuroprotective effects of minor components of virgin olive oil in rat brain tissue. Hydroxytyrosol ethyl ether (HT, 2 OH), tyrosol ethyl ether (Ty, 1 OH) and 3,4-di-ortho-methylidene-hydroxytyrosol ethyl ether (MET, no OH) were compared. Oxidative stress was induced with ferrous salts (lipid peroxidation induction), diethylmaleate (depletion of glutathione) and hypoxia-reoxygenation in brain slices. Lipid peroxidation was inhibited in direct proportion to the number of OH groups: HT>Ty>MET. Exposure to HT led to partial recovery of the glutathione system after chemical inhibition or hypoxia-reoxygenation. All three compounds inhibited cell death in hypoxia-reoxygenation experiments (HT≥Ty>MET). Peroxynitrite formation (3-nitrotyrosine) and inflammatory mediators (prostaglandin E2 and interleukin 1ß) were inhibited by all three compounds. In conclusion, the presence of OH groups in the molecule of these phenolic compounds from virgin olive oil is a determinant factor in their antioxidant effect in brain tissue, but this antioxidant effect is not the only explanation for their neuroprotective effect. Copyright © 2015. Published by Elsevier Inc.

Olive leaf extract activity against Candida albicans and C. dubliniensis - the in vitro viability study.

PubMed

Zorić, Nataša; Kopjar, Nevenka; Kraljić, Klara; Oršolić, Nada; Tomić, Siniša; Kosalec, Ivan

2016-09-01

Olive leaf extract is characterized by a high content of polyphenols (oleuropein, hydroxytyrosol and their derivatives), which is associated with its therapeutic properties. The objective of the present research was to evaluate the antifungal activity of olive leaf extract against Candida albicans ATCC 10231 and C. dubliniensis CBS 7987 strains. Minimum inhibitory concentrations (MIC) of the extract were determined by several in vitro assays. The extract showed a concentration depended effect on the viability of C. albicans with MIC value of 46.875 mg mL-1 and C. dubliniensis with MIC value 62.5 mg mL-1. Most sensitive methods for testing the antifungal effect of the extracts were the trypan blue exclusion method and fluorescent dye exclusion method while MIC could not be determined by the method according to the EUCAST recommendation suggesting that herbal preparations contain compounds that may interfere with this susceptibility testing. The fluorescent dye exclusion method was also used for the assessment of morphological changes in the nuclei of treated cells. According to the obtained results, olive leaf extract is less effective against the tested strains than hydroxytyrosol, an olive plant constituent tested in our previous study.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

PubMed

Lockyer, Stacey; Corona, Giulia; Yaqoob, Parveen; Spencer, Jeremy P E; Rowland, Ian

2015-07-14

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

Antimicrobial activity of Olea europaea Linné extracts and their applicability as natural food preservative agents.

PubMed

Thielmann, J; Kohnen, S; Hauser, C

2017-06-19

The antimicrobial activity of phenolic compounds from Olea (O.) europaea Linné (L.) is part of the scientific discussion regarding the use of natural plant extracts as alternative food preservative agents. Although, the basic knowledge on the antimicrobial potential of certain molecules such as oleuropein, hydroxytyrosol or elenolic acid derivatives is given, there is still little information regarding their applicability for food preservation. This might be primarily due to the lack of information regarding the full antimicrobial spectrum of the compounds, their synergisms in natural or artificial combinations and their interaction with food ingredients. The present review accumulates available literature from the past 40 years, investigating the antimicrobial activity of O. europaea L. derived extracts and compounds in vitro and in food matrices, in order to evaluate their food applicability. In summary, defined extracts from olive fruit or leaves, containing the strongest antimicrobial compounds hydroxytyrosol, oleacein or oleacanthal in considerable concentrations, appear to be suitable for food preservation. Nonetheless there is still need for consequent research on the compounds activity in food matrices, their effect on the natural microbiota of certain foods and their influence on the sensorial properties of the targeted products. Copyright © 2017 Elsevier B.V. All rights reserved.

High-resolution mass spectrometry to evaluate the influence of cross-breeding segregating populations on the phenolic profile of virgin olive oils.

PubMed

Sánchez de Medina, Verónica; Calderón-Santiago, Mónica; El Riachy, Milad; Priego-Capote, Feliciano; Luque de Castro, María Dolores

2014-12-01

The growing demand for high-quality virgin olive oils (VOOs) has increased the interest in olive breeding programs. Cross-breeding is considered, within these programs, the best strategy to generate new cultivars as an attempt to improve the present cultivars. In this research, the phenolic profile of VOOs from target crosses (Arbequina × Arbosana, Picual × Koroneiki and Sikitita × Arbosana) and their corresponding genitors (Arbequina, Arbosana, Koroneiki, Picual and Sikitita) has been evaluated using a targeted metabolomics approach. The phenolic profiles were obtained by liquid chromatographic-hybrid quadrupole time-of-flight mass spectrometric targeted analysis of 37 phenols or compounds involved in the main pathways for their biosynthesis. Statistical multivariate analysis by principal component analysis was applied to study the influence of genotype on phenol composition. Phenolic compounds with the highest contribution to explain the observed variability associated to genotype were identified through fold change algorithms (cut-off > 2.0) and t-test analysis. A total of nine phenols (viz. quercetin, ligstroside aglycon (p-HPEA-EA), demethyl oleuropein aglycon, oleuropein aglycon (3,4-DHPEA-EA), hydroxypinoresinol, hydroxytyrosol and phenolic acids such as p-coumaric acid, ferulic acid and protocatechuic acid) contributed to explain the observed variability with 99% confidence (P<0.01). © 2014 Society of Chemical Industry.

Direct study of minor extra-virgin olive oil components without any sample modification. 1H NMR multisupression experiment: A powerful tool.

PubMed

Ruiz-Aracama, Ainhoa; Goicoechea, Encarnación; Guillén, María D

2017-08-01

Proton Nuclear Magnetic Resonance ( 1 H NMR) was employed to study monovarietal commercial Spanish extra-virgin olive oils (EVOO) (Arbequina, Arroniz, Cornicabra, Hojiblanca and Picual). Each sample was analyzed by a standard pulse and by an experiment suppressing the main lipid signals, enabling the detection of signals of minor components. The aim was to determine the possibilities of both 1 H NMR approaches to characterize EVOO composition, focusing on acyl groups, squalene, sterols, triterpene acids/esters, fatty alcohols, wax esters and phenols (lignans, tyrosol, hydroxytyrosol, oleocanthal, oleacein, oleokoronal, oleomissional, ligstrodials and oleuropeindials), and to determine hydrolysis and oxidation levels. The signal assignments (in deuterated chloroform) are thoroughly described, identifying for the first time those of the protons of esters of phytol and of geranylgeraniol. Correct signal assignment is fundamental for obtaining sound results when interpreting statistical data from metabolomic studies of EVOO composition and adulteration, making it possible to differentiate and classify oils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of the antioxidant and antibacterial activities of different olive processing wastewaters

PubMed Central

Tan, Shiau Pin; El-Abbassi, Abdelilah; Kiai, Hajar; Hafidi, Abdellatif; O’Donovan, Orla; McLoughlin, Peter

2017-01-01

Olive processing wastewaters (OPW), namely olive mill wastewater (OMW) and table-olive wastewaters (TOW) were evaluated for their antibacterial activity against five Gram-positive and two Gram-negative bacteria using the standard disc diffusion and thin layer chromatography (TLC)-bioautography assays. Disc diffusion screening and bioautography of OMW were compared to the phenolic extracts of table-olive brines. Positive activity against S. aureus was demonstrated. The optimization of chromatographic separation revealed that hexane/acetone in the ratio of 4:6 was the most effective for phenolic compounds separation. A HPLC-MS analysis was performed showing that only two compounds, hydroxytyrosol and tyrosol, were the predominant phenolic compounds in all OPW. The phenolic extract of OMW generated by a semi-modern process showed the highest free radical-scavenging activity (DPPH assay) compared to the other phenolic extracts. It is apparent from the present study that OPW are a rich source of antioxidants suitable for use in food, cosmetic or pharmaceutical applications. PMID:28873097

Changes in Phenolic Compounds and Phytotoxicity of the Spanish-Style Green Olive Processing Wastewaters by Aspergillus niger B60.

PubMed

Papadaki, Eugenia; Tsimidou, Maria Z; Mantzouridou, Fani Th

2018-05-16

This study systematically investigated the degradation kinetics and changes in the composition of phenolic compounds in Spanish-style Chalkidiki green olive processing wastewaters (TOPWs) during treatment using Aspergillus niger B60. The fungal growth and phenol degradation kinetics were described sufficiently by the Logistic and Edward models, respectively. The maximum specific growth rate (2.626 1/d) and the maximum degradation rate (0.690 1/h) were observed at 1500 mg/L of total polar phenols, indicating the applicability of the process in TOPWs with a high concentration of phenolic compounds. Hydroxytyrosol and the other simple phenols were depleted after 3-8 days. The newly formed secoiridoid derivatives identified by HPLC-DAD-FLD and LC-MS are likely produced by oleoside and oleuropein aglycon via the action of fungal β-glucosidase and esterase. The treated streams were found to be less phytotoxic with reduced chemical oxygen demand by up to 76%. Findings will provide useful information for the subsequent treatment of residual contaminants.

Plant Phenols as Antibiotic Boosters: In Vitro Interaction of Olive Leaf Phenols with Ampicillin.

PubMed

Lim, Anxy; Subhan, Nusrat; Jazayeri, Jalal A; John, George; Vanniasinkam, Thiru; Obied, Hassan K

2016-03-01

The antimicrobial properties of olive leaf extract (OLE) have been well recognized in the Mediterranean traditional medicine. Few studies have investigated the antimicrobial properties of OLE. In this preliminary study, commercial OLE and its major phenolic secondary metabolites were evaluated in vitro for their antimicrobial activities against Escherichia coli and Staphylococcus aureus, both individually and in combination with ampicillin. Besides luteolin 7-O-glucoside, OLE and its major phenolic secondary metabolites were effective against both bacteria, with more activity on S. aureus. In combination with ampicillin, OLE, caffeic acid, verbascoside and oleuropein showed additive effects. Synergistic interaction was observed between ampicillin and hydroxytyrosol. The phenolic composition of OLE and the stability of olive phenols in assay medium were also investigated. While OLE and its phenolic secondary metabolites may not be potent enough as stand-alone antimicrobials, their abilities to boost the activity of co-administered antibiotics constitute an imperative future research area. Copyright © 2016 John Wiley & Sons, Ltd.

Obtaining sugars and natural antioxidants from olive leaves by steam-explosion.

PubMed

Romero-García, Juan Miguel; Lama-Muñoz, Antonio; Rodríguez-Gutiérrez, Guillermo; Moya, Manuel; Ruiz, Encarnación; Fernández-Bolaños, Juan; Castro, Eulogio

2016-11-01

In this work, steam-explosion treatment was evaluated as a procedure to recover sugars and natural antioxidants from olive tree leaves. The treatment was carried out following a Box-Behnken experimental design, with three factors, temperature (180-220°C), process time (2-10min) and milling time (0-15s). Response surface methodology showed that temperature was the most influential factor, followed by process time, while the best results were achieved with whole leaves. The operational conditions for simultaneously maximizing the sugars and natural antioxidants recoveries resulted to be 180°C, 8.3min and whole leaf; under these conditions 18.39g and 1950mg were obtained from 100g dry olive leaves, respectively. This is equivalent to 70% recovery of the initial sugars present in olive leaves, with a very low formation of inhibitory compounds and an important amount of natural products with antioxidant capacity such as oleuropein, hydroxytyrosol and flavonoids. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enzymatic hydrolysis of oleuropein from Olea europea (olive) leaf extract and antioxidant activities.

PubMed

Yuan, Jiao-Jiao; Wang, Cheng-Zhang; Ye, Jian-Zhong; Tao, Ran; Zhang, Yu-Si

2015-02-11

Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC50 = 41.82 μg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods.

Key process parameters involved in the treatment of olive mill wastewater by membrane bioreactor.

PubMed

Jaouad, Y; Villain-Gambier, M; Mandi, L; Marrot, B; Ouazzani, N

2018-04-18

The Olive Mill Wastewater (OMWW) biodegradation in an external ceramic membrane bioreactor (MBR) was investigated with a starting acclimation step with a Ultrafiltration (UF) membrane (150 kDa) and no sludge discharge in order to develop a specific biomass adapted to OMWW biodegradation. After acclimation step, UF was replaced by an Microfiltration (MF) membrane (0.1 µm). Sludge Retention Time (SRT) was set around 25 days and Food to Microorganisms ratio (F/M) was fixed at 0.2 kg COD  kg MLVSS -1  d -1 . At stable state, removal of the main phenolic compounds (hydroxytyrosol and tyrosol) and Chemical Oxygen Demand (COD) were successfully reached (95% both). Considered as a predominant fouling factor, but never quantified in MBR treated OMWW, Soluble Microbial Products (SMP) proteins, polysaccharides and humic substances concentrations were determined (80, 110 and 360 mg L -1 respectively). At the same time, fouling was easily managed due to favourable hydraulic conditions of external ceramic MBR. Therefore, OMWW could be efficiently and durably treated by an MF MBR process under adapted operating parameters.

Recovering Bioactive Compounds from Olive Oil Filter Cake by Advanced Extraction Techniques

PubMed Central

Lozano-Sánchez, Jesús; Castro-Puyana, María; Mendiola, Jose A.; Segura-Carretero, Antonio; Cifuentes, Alejandro; Ibáñez, Elena

2014-01-01

The potential of by-products generated during extra-virgin olive oil (EVOO) filtration as a natural source of phenolic compounds (with demonstrated bioactivity) has been evaluated using pressurized liquid extraction (PLE) and considering mixtures of two GRAS (generally recognized as safe) solvents (ethanol and water) at temperatures ranging from 40 to 175 °C. The extracts were characterized by high-performance liquid chromatography (HPLC) coupled to diode array detection (DAD) and electrospray time-of-flight mass spectrometry (HPLC-DAD-ESI-TOF/MS) to determine the phenolic-composition of the filter cake. The best isolation procedure to extract the phenolic fraction from the filter cake was accomplished using ethanol and water (50:50, v/v) at 120 °C. The main phenolic compounds identified in the samples were characterized as phenolic alcohols or derivatives (hydroxytyrosol and its oxidation product), secoiridoids (decarboxymethylated and hydroxylated forms of oleuropein and ligstroside aglycones), flavones (luteolin and apigenin) and elenolic acid derivatives. The PLE extraction process can be applied to produce enriched extracts with applications as bioactive food ingredients, as well as nutraceuticals. PMID:25226536

Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity.

PubMed

Rahmani, Arshad H; Albutti, Aqel S; Aly, Salah M

2014-01-01

The current mode of treatment for various diseases is based on synthetic drugs are effective but they show adverse effect and also alter the genetic and metabolic activity. Moreover, some drugs prepared from plants and their constituents show potentiality with more efficacy than synthetic agents used in clinical therapy. Earlier report has shown that regular consumption of fruits and vegetables is strongly related with reduced risk of developing various diseases. Several epidemiological studies has shown that, the incidence heart disease and cancers is lowest in the Mediterranean basin as compared to the part of the world because of their diet rich in olives and olive products. Olives are commonly consumed in Mediterranean and Arabian Peninsula and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that, the constituents from olive such as oleuropein, squalene and hydroxytyrosol modulate the genes functions and other activities. In this review, the medicinal value of olives and their constituents are summarized in terms of therapeutic approach in the diseases management through regulation of various activities.

Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity

PubMed Central

Rahmani, Arshad H; Albutti, Aqel S; Aly, Salah M

2014-01-01

The current mode of treatment for various diseases is based on synthetic drugs are effective but they show adverse effect and also alter the genetic and metabolic activity. Moreover, some drugs prepared from plants and their constituents show potentiality with more efficacy than synthetic agents used in clinical therapy. Earlier report has shown that regular consumption of fruits and vegetables is strongly related with reduced risk of developing various diseases. Several epidemiological studies has shown that, the incidence heart disease and cancers is lowest in the Mediterranean basin as compared to the part of the world because of their diet rich in olives and olive products. Olives are commonly consumed in Mediterranean and Arabian Peninsula and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that, the constituents from olive such as oleuropein, squalene and hydroxytyrosol modulate the genes functions and other activities. In this review, the medicinal value of olives and their constituents are summarized in terms of therapeutic approach in the diseases management through regulation of various activities. PMID:24955148

Comparative evaluation of maceration and ultrasonic-assisted extraction of phenolic compounds from fresh olives.

PubMed

Deng, Junlin; Xu, Zhou; Xiang, Chunrong; Liu, Jing; Zhou, Lijun; Li, Tian; Yang, Zeshen; Ding, Chunbang

2017-07-01

Ultrasonic-assisted extraction (UAE) and maceration extraction (ME) were optimized using response surface methodology (RSM) for total phenolic compounds (TPC) from fresh olives. The main phenolic compounds and antioxidant activity of TPC were also investigated. The optimized result for UAE was 22mL/g of liquid-solid ratio, 47°C of extraction temperature and 30min of extraction time, 7.01mg/g of yielding, and for ME was 24mL/g of liquid-solid ratio, 50°C of extraction temperature and 4.7h of extraction time, 5.18mg/g of yielding. The HPLC analysis revealed that the extracts by UAE and ME possessed 14 main phenolic compounds, and UAE exhibited more amounts of all phenols than ME. The most abundant phenolic compounds in olive extracts were hydroxytyrosol, oleuropein and rutin. Both extracts showed excellent antioxidant activity in a dose-dependent manner. Taken together, UAE could effectively increase the yield of phenolic compounds from olives. In addition these phenolic compounds could be used as a potential source of natural antioxidants. Copyright © 2017 Elsevier B.V. All rights reserved.

Biophenols: Enzymes (β-secretase, Cholinesterases, histone deacetylase and tyrosinase) inhibitors from olive (Olea europaea L.).

PubMed

Omar, Syed Haris; Scott, Christopher J; Hamlin, Adam S; Obied, Hassan K

2018-07-01

The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aβ) producing enzyme (β-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC 50 : 3.8 nM) followed by verbascoside (IC 50 : 6.3 nM) and olive fruit extract (IC 50 : 18 ng), respectively. Olive biophenol, quercetin exhibited strongest enzyme inhibitory activity against tyrosinase (IC 50 : 10.73 μM), BChE (IC 50 : 19.08 μM), AChE (IC 50 : 55.44 μM), and HDAC (IC 50 : 105.1 μM) enzymes. Furthermore, olive biophenol verbascoside (IC 50 : 188.6 μM), and hydroxytyrosol extreme extract (IC 50 : 66.22 μg) were showed the highest levels of inhibition against the HDAC enzyme. Neuroprotective capacity against levodopa-induced toxicity in neuroblastoma (SH-SY5Y) cells of olive biophenols were assessed, where rutin indicated the highest neuroprotection (74%), followed by caffeic acid (73%), and extract hydroxytyrosol extreme (97%), respectively. To the best of our knowledge, this is the first in vitro report on the enzymes inhibitory activity of olive biophenols. Taken together, our in vitro results data suggest that olive biophenols could be a promising natural inhibitor, which may reduce the enzyme-induced toxicity associated with the oxidative stress involved in the progression of AD. Acetylthiocholine iodide (PubChem CID: 74629); S-Butyrylthiocholine chloride (PubChem CID: 3015121); Caffeic acid (PubChem CID: 689043); Dimethyl sulfoxide (DMSO) (PubChem: 679); L-3,4-Dihydroxyphenylalanine (L-DOPA) (PubChem CID: 6047); 5,5'-Dithiobis (2-nitrobenzoic acid) (DTNB) (PubChem CID: 6254); Epigallocatechin gallate (EGCG) (PubChem CID: 65064); Ethylenediamine tetraacetic acid (EDTA) (PubChem CID: 6049); Galantamine hydrobromide (PubChem CID: 121587); l-Glutamine (PubChem CID: 5961); Hydroxytyrosol (PubChem CID: 82755); Kojic acid (PubChem CID: 3840); Luteolin (PubChem CID: 5280445); Oleuropein (PubChem CID: 5281544); Penicillin-streptomycin (PubChem CID: 131715954); Quercetin (PubChem CID: 5280343); Rutin (PubChem CID: 5280805); Tris-HCl buffer (PubChem: 93573); Trypan blue (PubChem: 9562061). Copyright © 2018 Elsevier B.V. All rights reserved.

Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.

PubMed

Je, In-Gyu; Kim, Duk-Sil; Kim, Sung-Wan; Lee, Soyoung; Lee, Hyun-Shik; Park, Eui Kyun; Khang, Dongwoo; Kim, Sang-Hyun

2015-01-01

Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

Transcriptomics and the Mediterranean Diet: A Systematic Review

PubMed Central

Herrera-Marcos, Luis V.; Lou-Bonafonte, José M.; Arnal, Carmen; Navarro, María A.; Osada, Jesús

2017-01-01

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases and cancer and in decreasing overall mortality. Nowadays, transcriptomics is gaining particular relevance due to the existence of non-coding RNAs capable of regulating many biological processes. The present work describes a systematic review of current evidence supporting the influence of the Mediterranean diet on transcriptomes of different tissues in various experimental models. While information on regulatory RNA is very limited, they seem to contribute to the effect. Special attention has been given to the oily matrix of virgin olive oil. In this regard, monounsaturated fatty acid-rich diets prevented the expression of inflammatory genes in different tissues, an action also observed after the administration of olive oil phenolic compounds. Among these, tyrosol, hydroxytyrosol, and secoiridoids have been found to be particularly effective in cell cycle expression. Less explored terpenes, such as oleanolic acid, are important modulators of circadian clock genes. The wide range of studied tissues and organisms indicate that response to these compounds is universal and poses an important level of complexity considering the different genes expressed in each tissue and the number of different tissues in an organism. PMID:28486416

Olive Oil Phenolics Prevent Oxysterol‐Induced Proinflammatory Cytokine Secretion and Reactive Oxygen Species Production in Human Peripheral Blood Mononuclear Cells, Through Modulation of p38 and JNK Pathways

PubMed Central

Deiana, Monica; Spencer, Jeremy P. E.; Corona, Giulia

2017-01-01

Scope The aim of the present study was to investigate the ability of extra virgin olive oil (EVOO) polyphenols to counteract the proinflammatory effects induced by dietary and endogenous oxysterols in ex vivo immune cells. Methods and results Peripheral blood mononuclear cells (PBMCs), separated from the whole blood of healthy donors, were utilized and were stimulated with an oxysterols mixture, in the presence of physiologically relevant concentrations of the EVOO polyphenols, hydroxytyrosol, tyrosol, and homovanillic alcohol. Oxysterols significantly increased the production of proinflammatory cytokines, interleukin‐1β, regulated on activation, normal T‐cell expressed and secreted and macrophage migration inhibitory factor in ex vivo cultured PBMCs. Increased levels of reactive oxygen species (ROS) were also detected along with increased phosphorylation of the p38 and JNK. All phenolic compounds significantly reduced cytokine secretion induced by the oxysterols and inhibited ROS production and mitogen activated protein kinase phosphorylation. Conclusions These results suggest that extra virgin olive oil polyphenols modulate the immune response induced by dietary and endogenous cholesterol oxidation products in human immune cells and may hold benefit in controlling chronic immune and/or inflammatory processes. PMID:28815947

Transcriptomics and the Mediterranean Diet: A Systematic Review.

PubMed

Herrera-Marcos, Luis V; Lou-Bonafonte, José M; Arnal, Carmen; Navarro, María A; Osada, Jesús

2017-05-09

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases and cancer and in decreasing overall mortality. Nowadays, transcriptomics is gaining particular relevance due to the existence of non-coding RNAs capable of regulating many biological processes. The present work describes a systematic review of current evidence supporting the influence of the Mediterranean diet on transcriptomes of different tissues in various experimental models. While information on regulatory RNA is very limited, they seem to contribute to the effect. Special attention has been given to the oily matrix of virgin olive oil. In this regard, monounsaturated fatty acid-rich diets prevented the expression of inflammatory genes in different tissues, an action also observed after the administration of olive oil phenolic compounds. Among these, tyrosol, hydroxytyrosol, and secoiridoids have been found to be particularly effective in cell cycle expression. Less explored terpenes, such as oleanolic acid, are important modulators of circadian clock genes. The wide range of studied tissues and organisms indicate that response to these compounds is universal and poses an important level of complexity considering the different genes expressed in each tissue and the number of different tissues in an organism.

Chemical and sensory differences between high price and low price extra virgin olive oils.

PubMed

Fiorini, Dennis; Boarelli, Maria Chiara; Conti, Paolo; Alfei, Barbara; Caprioli, Giovanni; Ricciutelli, Massimo; Sagratini, Gianni; Fedeli, Donatella; Gabbianelli, Rosita; Pacetti, Deborah

2018-03-01

The aim of the study was to identify new potential chemical markers of extra virgin olive oil (EVOO) quality by using a multicomponent analysis approach. Sixty-six EVOOs were purchased from the Italian market and classified according to their price as low price EVOOs (LEVOOs) and high price EVOOs (HEVOOs) costing 3.60-5.90euro/L and 7.49-29.80euro/L respectively. Sensory and chemical parameters strictly related to olive oil quality have been investigated, like volatile substances, polar phenolic substances, antioxidant activity, fatty acid composition, and α-tocopherol. Significant differences in terms of chemical composition and sensory features have been highlighted between the two EVOOs classes investigated, proving a generally lower level of quality of LEVOOs, clearly showed also by means of principal component analysis. Among the most interesting outcomes, R ratio (free tyrosol and hydroxytyrosol over total free and bound forms), measuring the extent of secoiridoids hydrolysis, resulted to be significantly higher in LEVOOs than in HEVOOs. Other key differences were found in the volatile substances composition, in the stearic acid percentage and in p-coumaric acid content. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical and cellular antioxidant activity of phytochemicals purified from olive mill waste waters.

PubMed

Angelino, Donato; Gennari, Lorenzo; Blasa, Manuela; Selvaggini, Roberto; Urbani, Stefania; Esposto, Sonia; Servili, Maurizio; Ninfali, Paolino

2011-03-09

The isolation and identification of a phytocomplex from olive mill waste waters (OMWW) was achieved. The isolated phytocomplex is made up of the following three phenolic compounds: hydroxytyrosol (3,4-DHPEA), tyrosol (p-HPEA) and the dialdehydic form of decarboxymethyl elenolic acid, linked with (3,4-dihydroxyphenyl)ethanol (3,4-DHPEA-EDA). The purification of this phytocomplex was reached by partial dehydration of the OMWW, followed by liquid-liquid extraction with ethyl acetate and middle pressure liquid chromatography (MPLC) on a Sephadex LH-20 column. The phytocomplex accounted for 6% of the total phenolic content of the OMWW. The phytocomplex and individual compounds were tested for antioxidant capacity by the oxygen radical absorbance capacity (ORAC) method. The ORAC phytocomplex produced 10,000 ORAC units/g dry weight, whereas the cellular antioxidant activity, measured by the cellular antioxidant activity in red blood cell (CAA-RBC) method, demonstrated that the phytocomplex and all of the components are able to permeate the cell membrane thus exhibiting antioxidant activity inside the red blood cells. Our phytocomplex could be employed in the formulation of fortified foods and nutraceuticals, with the goal to obtain substantial health protective effects due to the suitable combination of the component molecules.

Variability of Virgin Olive Oil Phenolic Compounds in a Segregating Progeny from a Single Cross in Olea europaea L. and Sensory and Nutritional Quality Implications

PubMed Central

Pérez, Ana G.; León, Lorenzo; Pascual, Mar; Romero-Segura, Carmen; Sánchez-Ortiz, Araceli; de la Rosa, Raúl; Sanz, Carlos

2014-01-01

Virgin olive oil phenolic compounds are responsible for its nutritional and sensory quality. The synthesis of phenolic compounds occurs when enzymes and substrates meet as olive fruit is crushed during the industrial process to obtain the oil. The genetic variability of the major phenolic compounds of virgin olive oil was studied in a progeny of the cross of Picual x Arbequina olive cultivars (Olea europaea L.). They belong to four different groups: compounds that included tyrosol or hydroxytyrosol in their molecules, lignans, flavonoids, and phenolic acids. Data of phenolics in the oils showed that the progeny displayed a large degree of variability, widely transgressing the genitor levels. This high variability can be of interest on breeding programs. Thus, multivariate analysis allowed to identify genotypes within the progeny particularly interesting in terms of phenolic composition and deduced organoleptic and nutritional quality. The present study has demonstrated that it is possible to obtain enough degree of variability with a single cross of olive cultivars for compounds related to the nutritional and organoleptic properties of virgin olive oil. PMID:24651694

Variability of virgin olive oil phenolic compounds in a segregating progeny from a single cross in Olea europaea L. and sensory and nutritional quality implications.

PubMed

Pérez, Ana G; León, Lorenzo; Pascual, Mar; Romero-Segura, Carmen; Sánchez-Ortiz, Araceli; de la Rosa, Raúl; Sanz, Carlos

2014-01-01

Virgin olive oil phenolic compounds are responsible for its nutritional and sensory quality. The synthesis of phenolic compounds occurs when enzymes and substrates meet as olive fruit is crushed during the industrial process to obtain the oil. The genetic variability of the major phenolic compounds of virgin olive oil was studied in a progeny of the cross of Picual x Arbequina olive cultivars (Olea europaea L.). They belong to four different groups: compounds that included tyrosol or hydroxytyrosol in their molecules, lignans, flavonoids, and phenolic acids. Data of phenolics in the oils showed that the progeny displayed a large degree of variability, widely transgressing the genitor levels. This high variability can be of interest on breeding programs. Thus, multivariate analysis allowed to identify genotypes within the progeny particularly interesting in terms of phenolic composition and deduced organoleptic and nutritional quality. The present study has demonstrated that it is possible to obtain enough degree of variability with a single cross of olive cultivars for compounds related to the nutritional and organoleptic properties of virgin olive oil.

[Main pharmacokinetic parameters of p-tyrosol after intravenous injection in rats. Part III: Distribution of p-tyrosol in rat].

PubMed

Chernyshova, G A; Plotnikov, M B; Smol'iakova, V I; Krasnov, E A

2011-01-01

Distribution of p-tyrosol in organism was studied in rats after a single intravenous administration in a dose of 200 mg/kg. It was shown that p-tyrosol rapidly penetrates into well perfused organs (brain, heart, kidneys). The maximum concentration ofp-tyrosol in these organs was determined in 1 minute after administration, and the mean distribution constant was within 0.8-1.11. The albumin bound fraction ofp-tyrozol amounted to 0.26-0.30.

Components of a standardised olive leaf dry extract (Ph. Eur.) promote hypothiocyanite production by lactoperoxidase.

PubMed

Flemmig, Jörg; Rusch, Dorothea; Czerwińska, Monika Ewa; Rauwald, Hans-Wilhelm; Arnhold, Jürgen

2014-05-01

We investigated in vitro the ability of a standardised olive leaf dry extract (Ph. Eur.) (OLE) as well as of its single components to circumvent the hydrogen peroxide-induced inhibition of the hypothiocyanite-producing activity of lactoperoxidase (LPO). The rate of hypothiocyanite (⁻OSCN) formation by LPO was quantified by spectrophotometric detection of the oxidation of 5-thio-2-nitrobenzoic acid (TNB). By using excess hydrogen peroxide, we forced the accumulation of inactive enzymatic intermediates which are unable to promote the two-electronic oxidation of thiocyanate. Both OLE and certain extract components showed a strong LPO-reactivating effect. Thereby an o-hydroxyphenolic moiety emerged to be essential for a good reactivity with the inactive LPO redox states. This basic moiety is found in the main OLE components oleuropein, oleacein, hydroxytyrosol, caffeic acid as well as in different other constituents including the OLE flavone luteolin. As LPO is a key player in the humoral immune response, these results propose a new mode of action regarding the well-known bacteriostatic and anti-inflammatory properties of the leaf extract of Olea europaea L. Copyright © 2014 Elsevier Inc. All rights reserved.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation.

PubMed

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11-16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18-22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9-13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly.

A defence-related Olea europaea β-glucosidase hydrolyses and activates oleuropein into a potent protein cross-linking agent

PubMed Central

Koudounas, Konstantinos; Banilas, Georgios; Michaelidis, Christos; Demoliou, Catherine; Rigas, Stamatis; Hatzopoulos, Polydefkis

2015-01-01

Oleuropein, the major secoiridoid compound in olive, is involved in a sophisticated two-component defence system comprising a β-glucosidase enzyme that activates oleuropein into a toxic glutaraldehyde-like structure. Although oleuropein deglycosylation studies have been monitored extensively, an oleuropein β-glucosidase gene has not been characterized as yet. Here, we report the isolation of OeGLU cDNA from olive encoding a β-glucosidase belonging to the defence-related group of terpenoid-specific glucosidases. In planta recombinant protein expression assays showed that OeGLU deglycosylated and activated oleuropein into a strong protein cross-linker. Homology and docking modelling predicted that OeGLU has a characteristic (β/α)8 TIM barrel conformation and a typical construction of a pocket-shaped substrate recognition domain composed of conserved amino acids supporting the β-glucosidase activity and non-conserved residues associated with aglycon specificity. Transcriptional analysis in various olive organs revealed that the gene was developmentally regulated, with its transcript levels coinciding well with the spatiotemporal patterns of oleuropein degradation and aglycon accumulation in drupes. OeGLU upregulation in young organs reflects its prominent role in oleuropein-mediated defence system. High gene expression during drupe maturation implies an additional role in olive secondary metabolism, through the degradation of oleuropein and reutilization of hydrolysis products. PMID:25697790

Role of tyrosol on Candida albicans, Candida glabrata and Streptococcus mutans biofilms developed on different surfaces.

PubMed

Monteiro, Douglas Roberto; Arias, Laís Salomão; Fernandes, Renan Aparecido; Straioto, Fabiana Gouveia; Barros Barbosa, Débora; Pessan, Juliano Pelim; Delbem, Alberto Carlos Botazzo

2017-02-01

To assess the effect of tyrosol on the production of hydrolytic enzymes (by Candida biofilm cells) and acid (by Streptococcus mutans biofilms), as well as to quantify single and mixed biofilms of these species formed on acrylic resin (AR) and hydroxyapatite (HA). Candida and S. mutans biofilms were formed on AR and HA in the presence of tyrosol during 48 hours. Next, acid proteinase, phospholipase and hemolytic activities of Candida biofilm cells were determined, while acid production by S. mutans biofilms was assessed by pH determination. The effect of tyrosol on mature biofilms (96 hours) was evaluated through quantification of total biomass, metabolic activity, number of colony-forming units and composition of biofilms' extracellular matrix. Data were analyzed by one- and two-way ANOVA, followed by Tukey's and Holm-Sidak's tests (α = 0.05). Treatments with tyrosol were not able to significantly reduce hydrolytic enzymes and acid production by Candida and S. mutans. Tyrosol only significantly reduced the metabolic activity of single biofilms of Candida species. Tyrosol on its own had a limited efficacy against single and mixed-species oral biofilms. Its use as an alternative antimicrobial for topical therapies still demands more investigation.

Fast separation and determination of tyrosol, hydroxytyrosol and other phenolic compounds in extra-virgin olive oil by capillary zone electrophoresis with ultraviolet-diode array detection.

PubMed

Bonoli, Matteo; Montanucci, Marina; Gallina Toschi, Tullia; Lercker, Giovanni

2003-09-05

Olive oil is the main source of fat in the Mediterranean diet, and its consumption has been related to a low incidence of coronary heart disease and certain cancers. Recent findings demonstrate that olive oil phenolics are powerful in vitro and in vivo antioxidants and display other biological activities that could partially account for the observed healthful effects of the Mediterranean diet. A detailed method optimization plan was carried out to separate the most popular phenols in olive oil for four separation parameters: buffer concentration, buffer pH, applied voltage and temperature. Consequently, an analytical method capable of separating 21 different phenols and polyphenols by capillary zone electrophoresis was developed; the separation was performed within 10 min, using a 40 cm x 50 microm capillary, with a 45 mM sodium tetraborate buffer (pH 9.60), at 27 kV and 30 degrees C. The optimized method was applied to methanolic extracts of several Italian extra-virgin olive oils obtained by different technologies in order to characterize and to compare their antioxidant profile. Positive correlations of phenolic compounds found by capillary zone electrophoresis (CZE) and two colorimetric indexes (total polyphenols and o-diphenols) were found and discussed.

Use of solar distillation for olive mill wastewater drying and recovery of polyphenolic compounds.

PubMed

Sklavos, Sotirios; Gatidou, Georgia; Stasinakis, Athanasios S; Haralambopoulos, Dias

2015-10-01

Olive mill wastewater (OMW) is characterized by its high organic load and the presence of phenolic compounds. For first time, a solar distillator was used to investigate the simultaneous solar drying of OMW and the recovery of phenolic compounds with antioxidant properties in the distillate. Two experiments were conducted and the role of thermal insulation on the performance of the distiller was studied. The use of insulation resulted to higher temperatures in the distillator (up to 84.3 °C and 78.5 °C at the air and sludge, respectively), shorter period for OMW dewatering (14 days), while it increased the performance of distillator by 26.1%. Chemical characterization of the distillate showed that pH and COD concentration gradually decreased during the experiments, whereas an opposite trend was noticed for conductivity and total phenols concentration. Almost 4% of the total phenols found initially in OMW were transferred to the distillate when an insulated solar distillator was used. Gas chromatographic analysis of collected distillates confirmed the presence of tyrosol in all samples; whereas hydroxytyrosol was found only in fresh collected distillate samples. Further experiments should be conducted to optimize the process and quantify the concentrations of recovered phenolic compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protective effect of simple phenols from extravirgin olive oil against lipid peroxidation in intestinal Caco-2 cells.

PubMed

Deiana, Monica; Corona, Giulia; Incani, Alessandra; Loru, Debora; Rosa, Antonella; Atzeri, Angela; Paola Melis, M; Assunta Dessì, M

2010-10-01

Complex polyphenols present in extravirgin olive oil are not directly absorbed, but undergo gastrointestinal biotransformation, increasing the relative amount of tyrosol (TYR) and hydroxytyrosol (HT) entering the small and large intestine. We investigated the capacity of TYR and HT to inhibit the insult of dietary lipid hydroperoxydes on the intestinal mucosa, using cultures of Caco-2, a cell line with enterocyte-like features, and studying the effect of tert-butyl hydroperoxide (TBH) treatment on specific cell membrane lipid targets. The effect of homovanillic alcohol (HVA), metabolite of HT in humans and detected as metabolite of HT in Caco-2 cells, was also evaluated. Exposure to TBH induced a significant increase of the level of MDA, the formation of fatty acid hydroperoxides and 7-ketocholesterol and the loss of α-tocopherol. Pretreatment with both HT and HVA protected Caco-2 cells from oxidative damage: there was no significant detection of oxidation products and the level of α-tocopherol was preserved. Noteworthy, TYR also exerted a protective action against fatty acids degradation. In vitro trials, where the simple phenols were tested during linoleic acid and cholesterol oxidation, gave evidence of a direct scavenging of peroxyl radicals and suggested a hydrogen atom-donating activity. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of Olive Oil Phenolic Compounds on Inflammation in the Prevention and Treatment of Coronary Artery Disease

PubMed Central

de Souza, Priscilla Azambuja Lopes; Marcadenti, Aline; Portal, Vera Lúcia

2017-01-01

Coronary artery disease (CAD) is responsible for more than 7 million deaths worldwide. In the early stages of the development of atherosclerotic plaques, cardiovascular risk factors stimulate vascular endothelial cells, initiating an inflammatory process, fundamental in the pathogenesis of CAD. The inclusion of potentially cardioprotective foods, such as olive oil, to the diet, may aid in the control of these risk factors, and in the reduction of cytokines and inflammatory markers. The present review aims to address the interaction between phenolic compounds present in olive oil, and inflammation, in the prevention and treatment of CAD. In vitro and in vivo studies suggest that phenolic compounds, such as hydroxytyrosol, tyrosol, and their secoiridoid derivatives, may reduce the expression of adhesion molecules and consequent migration of immune cells, modify the signaling cascade and the transcription network (blocking the signal and expression of the nuclear factor kappa B), inhibit the action of enzymes responsible for the production of eicosanoids, and consequently, decrease circulating levels of inflammatory markers. Daily consumption of olive oil seems to modulate cytokines and inflammatory markers related to CAD in individuals at risk for cardiovascular diseases. However, clinical studies that have evaluated the effects of olive oil and its phenolic compounds on individuals with CAD are still scarce. PMID:28973999

Olive Oil and its Potential Effects on Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Antony, Shan; Zhang, G. P.

Alzheimer's disease is a neuro-degenerative brain disease that is responsible for affecting the lives of hundreds of thousands of people every year. There has been no evidence to suggest a cure for the disease and the only existing treatments have very low rates of success in trial patients. This is largely due to the fact that the brain is one of the most undiscovered parts of the human body. Brain chemistry is highly complex and responds to its environment in random and radical ways. My research includes testing the reactionary outcomes of combining compounds of olive oil with the 20 basic amino acids. Regions around the world with olive oil based diets show a direct correlation to lower rates of Alzheimer's. Testing few compounds of olive oil with chemicals already found in the brain may yield to a better understanding as to why that is. I took the compounds tyrosol, hydroxytyrosol, and oleocanthal, and combined them with the 20 basic amino acids and calculated the total energy of the new molecule. The molecules produced with acceptably low energy values will be the center of further research. These molecules could lead to truly understanding olive oil's effect on the brain, and ultimately, the cure or prevention of Alzheimer's disease.

[Simultaneously preparation of grams of high purity tyrosol, crenulatin and salidroside from Rhodiola crenulata].

PubMed

Luo, Xin; Wang, Xue-jing; Li, Shi-ping; Zhang, Qiao; Zhao, Yi-wu; Huang Wen-zhe; Wang, Zhen-zhong; Xiao, Wei

2015-04-01

Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside.

Hydroxytyrosol disposition in humans.

PubMed

Miro-Casas, Elisabet; Covas, Maria-Isabel; Farre, Magi; Fito, Montserrat; Ortuño, Jordi; Weinbrenner, Tanja; Roset, Pere; de la Torre, Rafael

2003-06-01

Animal and in vitro studies suggest that phenolic compounds in virgin olive oil are effective antioxidants. In animal and in vitro studies, hydroxytyrosol and its metabolites have been shown to be strong antioxidants. One of the prerequisites to assess their in vivo physiologic significance is to determine their presence in human plasma. We developed an analytical method for both hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma. The administered dose of phenolic compounds was estimated from methanolic extracts of virgin olive oil after subjecting them to different hydrolytic treatments. Plasma and urine samples were collected from 0 to 12 h before and after 25 mL of virgin olive oil intake, a dose close to that used as daily intake in Mediterranean countries. Samples were analyzed by capillary gas chromatography-mass spectrometry before and after being subjected to acidic and enzymatic hydrolytic treatments. Calibration curves were linear (r >0.99). Analytical recoveries were 42-60%. Limits of quantification were <1.5 mg/L. Plasma hydroxytyrosol and 3-O-methyl-hydroxytyrosol increased as a response to virgin olive oil administration, reaching maximum concentrations at 32 and 53 min, respectively (P <0.001 for quadratic trend). The estimated hydroxytyrosol elimination half-life was 2.43 h. Free forms of these phenolic compounds were not detected in plasma samples. The proposed analytical method permits quantification of hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma after real-life doses of virgin olive oil. From our results, approximately 98% of hydroxytyrosol appears to be present in plasma and urine in conjugated forms, mainly glucuronoconjugates, suggesting extensive first-pass intestinal/hepatic metabolism of the ingested hydroxytyrosol.

Oleuropein as a bioactive constituent added in milk and yogurt.

PubMed

Zoidou, Evangelia; Magiatis, Prokopios; Melliou, Eleni; Constantinou, Maria; Haroutounian, Serkos; Skaltsounis, Alexios-Leandros

2014-09-01

Oleuropein is a bioactive natural product from olives known to display a broad variety of health beneficial properties. However its presence in most edible olives is lowered due to debittering. In this respect, we envisaged the incorporation of oleuropein into dairy products (cow's milk and yogurt) aiming to produce novel functional foods. Additionally, an analytical method for the monitoring of oleuropein in milk and yogurt was also developed and validated. Oleuropein was not affected during heat treatment of milk, while during the milk fermentation process it was not hydrolysed by the produced acids. Oleuropein was not metabolised by lactic acid bacteria, did not inhibit their growth and its stability in the final products was proven. The novel products displayed same taste, colour and texture as the conventional ones. Results herein indicate that oleuropein can be added as an active ingredient in milk and yogurt preparations to provide two novel functional dairy products. Copyright © 2014. Published by Elsevier Ltd.

Effect of Foods and β-Cyclodextrin on the Bioaccessibility and the Uptake by Caco-2 Cells of Hydroxytyrosol from Either a Pure Standard or Alperujo.

PubMed

Malapert, Aurélia; Tomao, Valérie; Dangles, Olivier; Reboul, Emmanuelle

2018-05-09

Hydroxytyrosol bioaccessibility and absorption by the intestinal cells were studied using an in vitro digestion model and Caco-2 TC7 monolayers cells in culture in the presence and absence of β-cyclodextrin and foods. Hydroxytyrosol was either provided as a pure standard or in an alperujo powder. The presence of foods significantly decreased hydroxytyrosol bioaccessibility and absorption (-20 and -10%, respectively), while β-cyclodextrin had no effect. Moreover, the presence of other compounds from alperujo in the intestinal compartment reduced hydroxytyrosol absorption by Caco-2 cells compared to pure standard (-60%). The final bioavailability of hydroxytyrosol, defined as its quantity at the basolateral side of cultured cell monolayers compared to the initial amount in the test meal, was 6.9 ± 0.4, 31.1 ± 1.1, and 40.9 ± 1.5% when hydroxytyrosol was from alperujo or a standard administered with or without food, respectively. Our results show that conversely to foods, β-cyclodextrin does not alter hydroxytyrosol bioavailability.

The effect of oleuropein from olive leaf (Olea europaea) extract on Ca²⁺ homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells.

PubMed

Cheng, Jin-Shiung; Chou, Chiang-Ting; Liu, Yuan-Yuarn; Sun, Wei-Chih; Shieh, Pochuen; Kuo, Daih-Huang; Kuo, Chun-Chi; Jan, Chung-Ren; Liang, Wei-Zhe

2016-05-01

Oleuropein, a phenolic compound found in the olive leaf (Olea europaea), has been shown to have biological activities in different models. However, the effects of oleuropein on Ca(2+) homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in liver cells have not been analyzed. Oleuropein induced [Ca(2+)]i rises only in HepG2 cells but not in AML12, HA22T or HA59T cells due to the different status of 3-hydroxy-3-methylglutaryl-CoA reductase expression. In HepG2 cells, this Ca(2+) signaling response was reduced by removing extracellular Ca(2+), and was inhibited by the store-operated Ca(2+) channel blockers 2-APB and SKF96365. In Ca(2+)-free medium, pretreatment with the ER Ca(2+) pump inhibitor thapsigargin abolished oleuropein-induced [Ca(2+)]i rises. Oleuropein induced cell cycle arrest which was associated with the regulation of p53, p21, CDK1 and cyclin B1 levels. Furthermore, oleuropein elevated intracellular ROS levels but reduced GSH levels. Treatment with the intracellular Ca(2+) chelator BAPTA-AM or the antioxidant NAC partially reversed oleuropein-induced cytotoxicity. Together, in HepG2 cells, oleuropein induced [Ca(2+)]i rises by releasing Ca(2+) from the ER and causing Ca(2+) influx through store-operated Ca(2+) channels. Moreover, oleuropein induced Ca(2+)-associated cytotoxicity that involved ROS signaling and cell cycle arrest. This compound may offer a potential therapy for treatment of human hepatoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

A systems biology approach to investigate the antimicrobial activity of oleuropein.

PubMed

Li, Xianhua; Liu, Yanhong; Jia, Qian; LaMacchia, Virginia; O'Donoghue, Kathryn; Huang, Zuyi

2016-12-01

Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by oleuropein for antimicrobial activities, little work has been done to integrate intracellular genes, enzymes and metabolic reactions for a systematic investigation of antimicrobial mechanism of oleuropein. In this study, the first genome-scale modeling method was developed to predict the system-level changes of intracellular metabolism triggered by oleuropein in Staphylococcus aureus, a common food-borne pathogen. To simulate the antimicrobial effect, an existing S. aureus genome-scale metabolic model was extended by adding the missing nitric oxide reactions, and exchange rates of potassium, phosphate and glutamate were adjusted in the model as suggested by previous research to mimic the stress imposed by oleuropein on S. aureus. The developed modeling approach was able to match S. aureus growth rates with experimental data for five oleuropein concentrations. The reactions with large flux change were identified and the enzymes of fifteen of these reactions were validated by existing research for their important roles in oleuropein metabolism. When compared with experimental data, the up/down gene regulations of 80% of these enzymes were correctly predicted by our modeling approach. This study indicates that the genome-scale modeling approach provides a promising avenue for revealing the intracellular metabolism of oleuropein antimicrobial properties.

A defence-related Olea europaea β-glucosidase hydrolyses and activates oleuropein into a potent protein cross-linking agent.

PubMed

Koudounas, Konstantinos; Banilas, Georgios; Michaelidis, Christos; Demoliou, Catherine; Rigas, Stamatis; Hatzopoulos, Polydefkis

2015-04-01

Oleuropein, the major secoiridoid compound in olive, is involved in a sophisticated two-component defence system comprising a β-glucosidase enzyme that activates oleuropein into a toxic glutaraldehyde-like structure. Although oleuropein deglycosylation studies have been monitored extensively, an oleuropein β-glucosidase gene has not been characterized as yet. Here, we report the isolation of OeGLU cDNA from olive encoding a β-glucosidase belonging to the defence-related group of terpenoid-specific glucosidases. In planta recombinant protein expression assays showed that OeGLU deglycosylated and activated oleuropein into a strong protein cross-linker. Homology and docking modelling predicted that OeGLU has a characteristic (β/α)8 TIM barrel conformation and a typical construction of a pocket-shaped substrate recognition domain composed of conserved amino acids supporting the β-glucosidase activity and non-conserved residues associated with aglycon specificity. Transcriptional analysis in various olive organs revealed that the gene was developmentally regulated, with its transcript levels coinciding well with the spatiotemporal patterns of oleuropein degradation and aglycon accumulation in drupes. OeGLU upregulation in young organs reflects its prominent role in oleuropein-mediated defence system. High gene expression during drupe maturation implies an additional role in olive secondary metabolism, through the degradation of oleuropein and reutilization of hydrolysis products. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Evidence of postprandial absorption of olive oil phenols in humans.

PubMed

Bonanome, A; Pagnan, A; Caruso, D; Toia, A; Xamin, A; Fedeli, E; Berra, B; Zamburlini, A; Ursini, F; Galli, G

2000-06-01

Olive oil phenols are potent antioxidants in vitro. If this were to be also demonstrated in vivo, it would help to explain the beneficial effects of this typical ingredient of the Mediterranean diet. This study was designed to determine the presence in lipoprotein fractions of two phenolic compounds peculiar to extra virgin olive oil, namely tyrosol and OH-tyrosol, and whether their absorption induces an antioxidant effect in vivo. Two trials were performed. In the first (Long-term), 14 healthy volunteers followed two diets, each for one month. The only difference between the diets was that the first supplied 50 g of extra virgin olive oil per day, where-as the second one supplied 50 g of refined olive oil with no simple phenols, as demonstrated by GC-MS analysis. There were no changes in LDL oxidizability and tyrosol and OH-tyrosol were not recovered in lipoproteins and plasma from fasting samples drawn at the end of each diet period. In the second study (Postprandial), eight healthy volunteers received an oral fat load consisting of 100 g of extra virgin olive oil. Blood was drawn at times 0', 30', 60', 120', 240', 360', and major plasma lipoprotein classes were separated. The concentration of tyrosol, OH-tyrosol and vitamin E was determined in lipoprotein fractions. Plasma antioxidant capacity was measured by a crocin-bleaching test and expressed as mM Trolox C equivalents. Tyrosol and OH-tyrosol were recovered in all lipoprotein fractions, except VLDL, with concentrations peaking between 60' and 120'. However, a very high variability in tyrosol and OH-tyrosol absorption was observed among subjects. Vitamin E content of LDL and HDL did not vary significantly throughout the study. Plasma antioxidant capacity increased significantly at time 120' (baseline 0.96 mM Trolox; 120' 1.19 mM Trolox; p = 0.02), and then returned almost to baseline values after 360' (1.1 mM Trolox). These findings suggest that phenolic compounds in olive oil are absorbed from the intestine, though not through a pathway dependent on chylomicron formation, and may exert a significant antioxidant effect in vivo, probably in the postprandial phase.

The Metabolism of Salidroside to Its Aglycone p-Tyrosol in Rats following the Administration of Salidroside

PubMed Central

Guo, Na; Zhu, Meixuan; Han, Xuejiao; Sui, Dan; Wang, Yang; Yang, Qian

2014-01-01

Salidroside is one of the major phenolic glycosides in Rhodiola, which has been reported to possess various biological activities. In the present study the in vivo deglycosylation metabolism of salidroside was investigated and its aglycone p-tyrosol but not the original salidroside was identified as the main form in rat tissues following the administration of salidroside. After the i.v. administration of salidroside at a dose of 50 mg/kg in rats, salidroside was quantified only in the liver, kidney and heart tissues. The highest level of p-tyrosol was detected in the heart, followed by the spleen, kidney, liver and lungs, in order. Salidroside was detected only in the liver, in contrast, p-tyrosol was detectable in most tissues except the brain, and the kidney tissues contained a significant amount of p-tyrosol compared to the other tissues after the i.g. administration of 100 mg/kg salidroside. The excretion behaviour revealed that the administrated salidroside mainly eliminated in the form of salidroside but not its aglycone metabolite p-tyrosol through urine. After i.v. and i.g. administration in rats, 64.00% and 23.80% of the total dose was excreted through urine in the form of salidroside, respectively. In addition, 0.19% and 2.25% of the dose was excreted in the form of p-tyrosol through urine after i.v. and i.g. administration, respectively. The faecal salidroside and p-tyrosol concentrations were 0.3% and 1.48% of the total dose after i.v. administration, respectively. After the i.g. administration of salidroside, trace salidroside and p-tyrosol were quantified in faeces within 72 h. In addition, the biliary excretion levels of salidroside after i.v. and i.g. administration were 2.86% and 0.02% of the dose, respectively. The obtained results show that salidroside was extensively metabolised to its aglycone p-tyrosol and distributed to various organs and the orginal salidroside was cleared rapidly through urine following the administration of salidroside. PMID:25101641

Spectroscopic and electrochemical studies of the interaction between oleuropein, the major bio-phenol in olives, and salmon sperm DNA

NASA Astrophysics Data System (ADS)

Mohamadi, Maryam; Afzali, Daryoush; Esmaeili-Mahani, Saeed; Mostafavi, Ali; Torkzadeh-Mahani, Masoud

2015-09-01

Interaction of oleuropein, the major bio-phenol in olive leaf and fruit, with salmon sperm double-stranded DNA was investigated by employing electronic absorption titrations, fluorescence quenching spectroscopy, competitive fluorescence spectroscopy, thermal denaturation and voltammetric studies. Titration of oleuropein with the DNA caused a hypochromism accompanied with a red shift indicating an intercalative mode of interaction. Binding constant of 1.4 × 104 M-1 was obtained for this interaction. From the curves of fluorescence titration of oleuropein with the DNA, binding constant and binding sites were calculated to be 8.61 × 103 M-1 and 1.05, respectively. Competitive studies with ethidium bromide (a well-known DNA intercalator) showed that the bio-phenol could take the place of ethidium bromide in the DNA intercalation sites. The interaction of oleuropein with DNA was also studied electrochemically. In the presence of the DNA, the anodic and cathodic peak currents of oleuropein decreased accompanied with increases in peak-to-peak potential separation and formal potential, indicating the intercalation of oleuropein into the DNA double helix. Moreover, melting temperature of the DNA was found to increase in the presence of oleuropein, indicating the stabilization of the DNA double helix due to an intercalative interaction.

Phenolic Compounds in Extra Virgin Olive Oil Stimulate Human Osteoblastic Cell Proliferation

PubMed Central

García-Martínez, Olga; De Luna-Bertos, Elvira; Ramos-Torrecillas, Javier; Ruiz, Concepción; Milia, Egle; Lorenzo, María Luisa; Jimenez, Brigida; Sánchez-Ortiz, Araceli; Rivas, Ana

2016-01-01

In this study, we aimed to clarify the effects of phenolic compounds and extracts from different extra virgin olive oil (EVOO) varieties obtained from fruits of different ripening stages on osteoblast cells (MG-63) proliferation. Cell proliferation was increased by hydroxytyrosol, luteolin, apigenin, p-coumaric, caffeic, and ferulic acids by approximately 11–16%, as compared with controls that were treated with one vehicle alone, while (+)-pinoresinol, oleuropein, sinapic, vanillic acid and derivative (vanillin) did not affect cell proliferation. All phenolic extracts stimulated MG-63 cell growth, and they induced higher cell proliferation rates than individual compounds. The most effective EVOO phenolic extracts were those obtained from the Picual variety, as they significantly increased cell proliferation by 18–22%. Conversely, Arbequina phenolic extracts increased cell proliferation by 9–13%. A decline in osteoblast proliferation was observed in oils obtained from olive fruits collected at the end of the harvest period, as their total phenolic content decreases at this late stage. Further research on the signaling pathways of olive oil phenolic compounds involved in the processes and their metabolism should be carried out to develop new interventions and adjuvant therapies using EVOO for bone health (i.e.osteoporosis) in adulthood and the elderly. PMID:26930190

Exploiting oleuropein for inhibiting collagen fibril formation.

PubMed

Bharathy, H; Fathima, N Nishad

2017-08-01

Collagen fibrils accumulate in excessive amounts and impair the normal functioning of the organ; therefore it stimulates the interest for identifying the compounds that could prevent the formation of fibrils. Herein, inhibition of self-assembly of collagen using oleuropein has been studied. The changes in the physico-chemical characteristics of collagen on interaction with increasing concentration of oleuropein has been studied using techniques like viscosity, UV-vis, CD and FT-IR. The inhibitory effect of oleuropein on fibril formation of collagen was proved using SEM. Circular dichroism and FT-IR spectra elucidates the alterations in the secondary structure of collagen suggesting non-covalent interactions between oleuropein and collagen. The decreased rate of collagen fibril formation also confirms the inhibition in the self-assembly of collagen. Hence, our study suggests that inhibition of the self-assembly process using oleuropein may unfold new avenues to treat fibrotic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Is dopamine behind the health benefits of red wine?

PubMed

de la Torre, Rafael; Covas, Maria Isabel; Pujadas, Maria Antonia; Fitó, Montserrat; Farré, Magí

2006-08-01

The contribution of biologically active non-nutrient chemicals to the health benefits of the Mediterranean diet is controversial because of their low dietary concentrations. Hydroxytyrosol is a dopamine metabolite, and also a very active naturally occurring phenol compound in olive oil. To examine the disposition of hydroxytyrosol in humans, given that we discovered its presence in red wine in the frame of the study. The pharmacokinetics of hydroxytyrosol from two clinical trials, designed to assess the short-term and postprandial effects of moderate doses of wine and olive oil in healthy volunteers, were compared. Despite a five-fold difference in the doses of hydroxytyrosol administered (0.35 mg for red wine and 1.7 mg for olive oil), urinary recoveries of hydroxytyrosol were higher after red wine administration. An interaction between ethanol and dopamine after red wine ingestion leading to the formation of hydroxytyrosol was observed. Biological effects after red wine ingestion should be re-examined on the basis of combined hydroxytyrosol concentrations from red wine and dopamine turnover.

Tyrosol and its analogues inhibit alpha-melanocyte-stimulating hormone induced melanogenesis.

PubMed

Wen, Kuo-Ching; Chang, Chih-Shiang; Chien, Yin-Chih; Wang, Hsiao-Wen; Wu, Wan-Chen; Wu, Chin-Sheng; Chiang, Hsiu-Mei

2013-11-28

Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis

PubMed Central

Wen, Kuo-Ching; Chang, Chih-Shiang; Chien, Yin-Chih; Wang, Hsiao-Wen; Wu, Wan-Chen; Wu, Chin-Sheng; Chiang, Hsiu-Mei

2013-01-01

Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents. PMID:24287915

Protective effects of oleuropein against renal injury oxidative damage in alloxan-induced diabetic rats; a histological and biochemical study.

PubMed

Ahmadvand, Hassan; Shahsavari, Gholamreza; Tavafi, Majid; Bagheri, Shahrokh; Moradkhani, Mohamad Reza; Kkorramabadi, Reza Mohammadrezaei; Khosravi, Peyman; Jafari, Maryam; Zahabi, Khadije; Eftekhar, Reza; Soleimaninejad, Maryam; Moghadam, Sanaz

2017-07-01

Oleuropein is a potent antioxidant and free-radical scavenger with antiinflammatory properties. In the present study, we evaluated the protective effects of oleuropein on myeloperoxidase (MPO) activity, nitrite, urea, creatinine and glomerulosclerosis in alloxan-induced type 1 diabetic rats. Thirty Sprague-Dawley male rats were randomly divided into 3 groups: group 1 as control; group 2 as untreated diabetic; and group 3 as treated with oleuropein 15 mg/kg i.p daily. Diabetes was induced in the second and third groups by subcutaneous alloxan injection. After 48 days, the animals were anaesthetized and then the livers and kidneys were removed immediately and used fresh or kept frozen until MPO activity analysis. Blood samples were also collected before sacrificing to measure nitrite, urea, and creatinine. Kidney paraffin sections were prepared to estimate glomerular volume, leukocyte infiltration, and glomerulosclerosis. Oleuropein significantly decreased leukocyte infiltration and glomerulosclerosis in the treated group compared with the diabetic untreated group. Oleuropein significantly decreased the levels of urea, nitrite, and creatinine in the treated group compared with the diabetic untreated group. Moreover, oleuropein significantly decreased MPO activity in the treated group compared with the diabetic untreated group. Oleuropein has antioxidative and antiatherogenic activities and exerts beneficial effects on inflammation and kidney function test and decreases diabetic complication in diabetic rats.

Development and Validation of a Combined Methodology for Assessing the Total Quality Control of Herbal Medicinal Products – Application to Oleuropein Preparations

PubMed Central

Lemonakis, Nikolaos; Gikas, Evagelos; Halabalaki, Maria; Skaltsounis, Alexios-Leandros

2013-01-01

Oleuropein (OE) is a secoiridoid glycoside, which occurs mostly in the Oleaceae family presenting several pharmacological properties, including antioxidant, cardio-protective, anti-atherogenic effects etc. Based on these findings OE is commercially available, as Herbal Medicinal Product (HMP), claimed for its antioxidant effects. As there are general provisions of the medicine regulating bodies e.g. European Medicines Agency, the quality of the HMP’s must always be demonstrated. Therefore, a novel LC-MS methodology was developed and validated for the simultaneous quantification of OE and its main degradation product, hydroxytyrosol (HT), for the relevant OE claimed HMP’s. The internal standard (IS) methodology was employed and separation of OE, HT and IS was achieved on a C18 Fused Core column with 3.1 min overall run time employing the SIM method for the analytical signal acquisition. The method was validated according to the International Conference on Harmonisation requirements and the results show adequate linearity (r2 > 0.99) over a wide concentration range [0.1–15 μg/mL (n=12)] and a LLOQ value of 0.1 μg/mL, for both OE and HT. Furthermore, as it would be beneficial to control the quality taking into account all the substances of the OE claimed HMP’s; a metabolomics-like approach has been developed and applied for the total quality control of the different preparations employing UHPLC-HRMS-multivariate analysis (MVA). Four OE-claimed commercial HMP’s have been randomly selected and MVA similarity-based measurements were performed. The results showed that the examined samples could also be differentiated as evidenced according to their scores plot. Batch to batch reproducibility between the samples of the same brand has also been determined and found to be acceptable. Overall, the developed combined methodology has been found to be an efficient tool for the monitoring of the HMP’s total quality. Only one OE HMP has been found to be consistent to its label claim. PMID:24205178

Selective ultrasound-enhanced enzymatic hydrolysis of oleuropein to its aglycon in olive (Olea europaea L.) leaf extracts.

PubMed

Delgado-Povedano, María Del Mar; Priego-Capote, Feliciano; Luque de Castro, María Dolores

2017-04-01

Hydrolysis of oleuropein, the main phenol in olive (Olea europaea L.) leaf extracts, to oleuropein aglycon and other subsequent products in the hydrolytic pathway can be catalyzed by different enzymes. Three of the most used hydrolases were assayed to catalyze the process, and β-glucosidase from Aspergillus niger was selected. Acceleration of the enzymatic hydrolysis by ultrasound (US) was studied using a Box-Behnken design (duty cycle, amplitude, cycle time) and an oleuropein standard, and the optimum US conditions for achieving maximum yield of oleuropein aglycon were 0.5s/s duty cycle, 50% amplitude and 45s cycle. The method was applied to obtain oleuropein aglycon from commercial and laboratory extracts from olive leaves, which may have a pharmacological use as deduced by its healthy properties. The kinetics of the US-assisted enzymatic hydrolysis was monitored by analysis of the target compounds using liquid chromatography-tandem mass spectrometry. Copyright © 2016 Elsevier Ltd. All rights reserved.

3,4-Dihydroxyphenylethanol (Hydroxytyrosol) Mitigates the Increase in Spontaneous Oxidation of Dopamine during Monoamine Oxidase Inhibition in PC12 Cells

PubMed Central

Goldstein, David S.; Jinsmaa, Yunden; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan

2016-01-01

The catecholaldehyde hypothesis predicts that monoamine oxidase (MAO) inhibition should slow the progression of Parkinson’s disease, by decreasing production of the autotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). Inhibiting MAO, however, diverts the fate of cytoplasmic dopamine toward potentially harmful spontaneous oxidation products, indicated by increased 5-S-cysteinyl-dopamine (Cys-DA) levels. 3,4-Dihydroxyphenylethanol (hydroxytyrosol) is an abundant anti-oxidant phenol in constituents of the Mediterranean diet. Whether hydroxytyrosol alters enzymatic or spontaneous oxidation of dopamine has been unknown. Rat pheochromocytoma PC12 cells were incubated with hydroxytyrosol (10 μM, 180 minutes) alone or with the MAO-A inhibitor clorgyline (1 nM) or the MAO-B inhibitors rasagiline or selegiline (0.5 μM). Hydroxytyrosol decreased levels of DOPAL by 30% and Cys-DA by 49% (p<0.0001 each). Co-incubation with hydroxytyrosol prevented the increases in Cys-DA seen with all 3 MAO inhibitors. Hydroxytyrosol therefore inhibits both enzymatic and spontaneous oxidation of endogenous dopamine and mitigates the increase in spontaneous oxidation during MAO inhibition. PMID:27220335

Cardioprotective and neuroprotective roles of oleuropein in olive

PubMed Central

Omar, Syed Haris

2010-01-01

Traditional diets of people living in the Mediterranean basin are, among other components, very rich in extra-virgin olive oil, the most typical source of visible fat. Olive is a priceless source of monounsaturated and di-unsaturated fatty acids, polyphenolic antioxidants and vitamins. Oleuropein is the main glycoside in olives and is responsible for the bitter taste of immature and unprocessed olives. Chemically, oleuropein is the ester of elenolic acid and 3,4-dihydroxyphenyl ethanol, which possesses beneficial effects on human health, such as antioxidant, antiatherogenic, anti-cancer, anti-inflammatory and antimicrobial properties. The phenolic fraction extracted from the leaves of the olive tree, which contains significant amounts of oleuropein, prevents lipoprotein oxidation. In addition, oleuropein has shown cardioprotective effect against acute adriamycin cardiotoxicity and an anti-ischemic and hypolipidemic activities. Recently, oleuropein has shown neuroprotection by forming a non-covalent complex with the Aβ peptide, which is a key hallmark of several degenerative diseases like Alzheimer and Parkinson. Thus, a large mass of research has been accumulating in the area of olive oil, in the attempt to provide evidence for the health benefits of olive oil consumption and to scientifically support the widespread adoption of traditional Mediterranean diet as a model of healthy eating. These results provide a molecular basis for some of the benefits potentially coming from oleuropein consumption and pave the way to further studies on the possible pharmacological use of oleuropein to prevent or to slow down the cardiovascular and neurodegenerative diseases. PMID:23964170

Application of dried spot cards as a rapid sample treatment method for determining hydroxytyrosol metabolites in human urine samples. Comparison with microelution solid-phase extraction.

PubMed

Serra, Aida; Rubió, Laura; Macià, Alba; Valls, Rosa-M; Catalán, Úrsula; de la Torre, Rafael; Motilva, Maria-José

2013-11-01

Two different rapid sample pretreatment strategies, dried spot cards, and microelution solid-phase extraction plates (μSPE), with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) have been developed and validated for the determination of hydroxytyrosol and its metabolites in spiked human urine samples. Hydroxytyrosol, hydroxytyrosol-3'-O-glucuronide, hydroxytyrosol-4'-O-glucuronide, hydroxytyrosol-3-O-sulphate, and homovanillic alcohol-4'-O-glucuronide were used as the target compounds. Using the FTA DMPK-A dried urine spot card under optimum conditions, with 5 μL of preconcentrated urine volume and 100 μL of methanol/water (50/50, v/v) as the elution solvent, the extraction recovery (%R) of the compounds studied was higher than 80%, and the matrix effect (%ME) was less than 8%. The stability of these cards and punching at the centre or side of the card were also studied, obtaining an excellent stability after 7 days of storage and complete homogeneity across the surface of the dried drop. The different μSPE parameters that affect the efficiency were also studied, and under optimum conditions, the %R and the %ME were higher than 70% and lower than 17%, respectively. The linearity range in dried urine spot cards was 2.5-20 μM for all the metabolites, with the exception of hydroxytyrosol-3-O-sulphate and hydroxytyrosol, which were 0.3-70 μM and 2.5-50 μM respectively. With regards to μSPE, the linearity range was 0.5-5 μM for all the studied compounds, except for hydroxytyrosol-3-O-sulphate, which was 0.08-5 μM. The quantification limits (LOQs) were 0.3-2.5 μM and 0.08-0.5 μM in dried spot cards and in μSPE, respectively. The two developed methods were then applied and compared for determining hydroxytyrosol and its metabolites in human 24 h-urine samples after a sustained consumption (21 days) of a phenol-enriched virgin olive oil. The metabolites identified were hydroxytyrosol in its glucuronide and sulphate forms, homovanillic alcohol in its glucuronide and sulphate forms, homovanillic acid sulphate and hydroxytyrosol acetate sulphate.

Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance.

PubMed

Sherif, Iman O; Al-Gayyar, Mohammed M H

2018-04-01

Oleuropein is considered as a new chemotherapeutic agent in human hepatocellular carcinoma (HCC) while, its exact underlying molecular mechanism still not yet explored. In addition, cisplatin is a standard anticancer drug against solid tumors with toxic side effects. Therefore, we conducted this study to assess antitumor activity of oleuropein either alone or in combination with cisplatin against HepG2, human HCC cell lines, via targeting pro-NGF/NGF signaling pathway. HepG2 cells were treated with cisplatin (20, 50, 100 μM) and oleuropein (100, 200, 300 and 400 μM) as well as some of the cells were treated with 50 μM cisplatin and different concentrations of oleuropein. Gene expressions of nerve growth factor (NGF), matrix metalloproteinase-7 (MMP-7) and caspase-3 were evaluated by real time-PCR. In addition, protein levels of NGF and pro-form of NGF (pro-NGF) were measured by ELISA while, nitric oxide (NO) content was determined colorimetrically. Cisplatin treatment showed a significant elevation of NO content and pro-NGF protein level with a marked reduction of NGF protein level in addition to the upregulation of caspase-3 along with downregulation of MMP-7 gene expressions in a dose-dependent manner. However, the combination of 50 μM cisplatin and 200 μM oleuropein showed the most potent effect on the molecular level when compared with oleuropein or cisplatin alone. Our results showed for the first time that the anti-tumor activity of oleuropein against HCC could be attributed to influencing the pro-NGF/NGF balance via affecting MMP-7 activity without affecting the gene expression of NGF. Concurrent treatment with both oleuropein and cisplatin could lead to more effective chemotherapeutic combination against HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Evidence of oleuropein degradation by olive leaf protein extract.

PubMed

De Leonardis, Antonella; Macciola, Vincenzo; Cuomo, Francesca; Lopez, Francesco

2015-05-15

The enzymatic activity of raw protein olive leaf extract has been investigated in vivo, on olive leaf homogenate and, in vitro with pure oleuropein and other phenolic substrates. At least two types of enzymes were found to be involved in the degradation of endogenous oleuropein in olive leaves. As for the in vitro experiments, the presence of active polyphenoloxidase and β-glucosidase was determined by HPLC and UV-Visible spectroscopy. Interestingly, both the enzymatic activities were found to change during the storage of olive leaves. Specifically, the protein extracts obtained from fresh leaves showed the presence of both the enzymatic activities, because oleuropein depletion occurred simultaneously with the formation of the oleuropein aglycon, 3,4-DHPEA-EA. In comparison leaves subjected to the drying process showed a polyphenoloxidase activity leading exclusively to the formation of oxidation products responsible for the typical brown coloration of the reaction solution. Copyright © 2014 Elsevier Ltd. All rights reserved.

GC-MS olfactometric and LC-DAD-ESI-MS/MS characterization of key odorants and phenolic compounds in black dry-salted olives.

PubMed

Selli, Serkan; Kelebek, Hasim; Kesen, Songul; Sonmezdag, Ahmet Salih

2018-02-01

Olives are processed in different ways depending on consumption habits, which vary between countries. Different de-bittering methods affect the aroma and aroma-active compounds of table olives. This study focused on analyzing the aroma and aroma-active compounds of black dry-salted olives using gas chromatography-mass spectrometry-olfactometry (GC-MS-O) techniques. Thirty-nine volatile compounds which they have a total concentration of 29 459 µg kg -1 , were determined. Aroma extract dilution analysis (AEDA) was used to determine key aroma compounds of table olives. Based on the flavor dilution (FD) factor, the most powerful aroma-active compounds in the sample were methyl-2-methyl butyrate (tropical, sweet; FD: 512) and (Z)-3-hexenol (green, flowery; FD: 256). Phenolic compounds in table olives were also analyzed by LC-DAD-ESI-MS/MS. A total of 20 main phenolic compounds were identified and the highest content of phenolic compound was luteolin-7-glucoside (306 mg kg -1 ), followed by verbascoside (271 mg kg -1 ), oleuropein (231 mg kg -1 ), and hydroxytyrosol (3,4-DHPEA) (221 mg kg -1 ). Alcohols, carboxylic acids, and lactones were qualitatively and quantitatively the dominant volatiles in black dry-salted olives. Results indicated that esters and alcohols were the major aroma-active compounds. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Selenium and sulphur derivatives of hydroxytyrosol: inhibition of lipid peroxidation in liver microsomes of vitamin E-deficient rats.

PubMed

Rodríguez-Gutiérrez, Guillermo; Rubio-Senent, Fátima; Gómez-Carretero, Antonio; Maya, Inés; Fernández-Bolaños, Juan; Duthie, Garry G; de Roos, Baukje

2018-05-28

The objective of this study was to evaluate the capacity of modified phenols synthesized from hydroxytyrosol, a natural olive oil phenol, specifically those containing a selenium or sulphur group, to inhibit lipid peroxidation. The compounds' abilities to inhibit lipid peroxidation in liver microsomes obtained from vitamin E-deficient rats were compared to hydroxytyrosol. All synthetic compounds had a significant higher ability to inhibit lipid peroxidation than hydroxytyrosol. Selenium derivates displayed a higher antioxidant activity than sulphur derivatives. In addition, the antioxidant activity increased with a higher number of heteroatoms in the hydroxytyrosol molecular structure. The study shows, for the first time, the ability of synthetic compounds, derived from the most active phenol present in olives in free form (hydroxytyrosol), and containing one or two atoms of sulphur or selenium, to inhibit the lipid peroxidation of vitamin E-deficient microsomes. The antioxidant activity of five thioureas, a disulfide, a thiol, three selenoureas, a diselenide, and a selenonium were evaluated and the results showed a higher inhibition of lipid peroxidation than the natural phenol. Selenium and sulphur derivatives of hydroxytyrosol are novel antioxidants with the potential to supplement the lack of vitamin E in the diet as natural alternatives for the prevention of diseases related to oxidative damage.

Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin

PubMed Central

Tong, Tao; Kim, Nahyun; Park, Taesun

2015-01-01

We observed that oleuropein, the main constituent of the leaves and unprocessed olive drupes of Olea europaea, protected mice from high-fat diet-induced adiposity by up-regulation of genes involved in Wnt10b-mediated signaling in adipose tissue. The activation of Wnt/β-catenin pathway is also well established to positively regulate the anagen phase of hair growth cycle in mice skin. Methodology and Principal Findings Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day) to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression. Conclusions and Significance These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue. PMID:26060936

Cardioprotective Effects of the Polyphenol Hydroxytyrosol from Olive Oil.

PubMed

Tejada, Silvia; Pinya, Samuel; Del Mar Bibiloni, Maria; Tur, Josep A; Pons, Antoni; Sureda, Antoni

2017-01-01

The Mediterranean diet includes olive oil as its primary source of fat. This diet is frequently associated to longevity and a lower incidence of chronic diseases due to its biological activities and health effects. Apart from oleic acid, olive oil contains many bioactive components including polyphenols that have been reported to exert antioxidant and anti-inflammatory activities. Polyphenols may almost in part be responsible for the protective effects against cardiovascular diseases associated with olive oil. To review and discuss the available literature on hydroxytyrosol effects as a cardioprotective agent. Moreover, we also discuss the chemistry, nutritional aspects and bioavailability of hydroxytyrosol. Hydroxytyrosol is one of the major phenolic compounds in olive oil and has demonstrated strong radical-scavenging properties. Several studies have been performed in order to look further into the effects of the polyphenol hydroxytyrosol in relation to cardiovascular events and illnesses in animal trials and in vitro. However, no clinical trials have focused on the specific action of hydroxytyrosol and cardiovascular diseases, although some are being undertaken to look at olive oil or olive leaf extract properties. Hydroxytyrosol from olive oil exerts antioxidant, anti-inflammatory, anti-platelet aggregation and ati-atherogenic activities in in vitro and animal models. However, its possible therapeutic use in humans requires additional clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification and Characterization of the Iridoid Synthase Involved in Oleuropein Biosynthesis in Olive (Olea europaea) Fruits*

PubMed Central

Kries, Hajo; Panara, Francesco; Baldoni, Luciana; O'Connor, Sarah E.; Osbourn, Anne

2016-01-01

The secoiridoids are the main class of specialized metabolites present in olive (Olea europaea L.) fruit. In particular, the secoiridoid oleuropein strongly influences olive oil quality because of its bitterness, which is a desirable trait. In addition, oleuropein possesses a wide range of pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. In accordance, obtaining high oleuropein varieties is a main goal of molecular breeding programs. Here we use a transcriptomic approach to identify candidate genes belonging to the secoiridoid pathway in olive. From these candidates, we have functionally characterized the olive homologue of iridoid synthase (OeISY), an unusual terpene cyclase that couples an NAD (P)H-dependent 1,4-reduction step with a subsequent cyclization, and we provide evidence that OeISY likely generates the monoterpene scaffold of oleuropein in olive fruits. OeISY, the first pathway gene characterized for this type of secoiridoid, is a potential target for breeding programs in a high value secoiridoid-accumulating species. PMID:26709230

Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Salidroside from Glucose.

PubMed

Jiang, Jingjie; Yin, Hua; Wang, Shuai; Zhuang, Yibin; Liu, Shaowei; Liu, Tao; Ma, Yanhe

2018-05-02

Salidroside is an important plant-derived aromatic compound with diverse biological properties. Because of inadequate natural resources, the supply of salidroside is currently limited. In this work, we engineered the production of salidroside in yeast. First, the aromatic aldehyde synthase (AAS) from Petroselinum crispum was overexpressed in Saccharomyces cerevisiae when combined with endogenous Ehrlich pathway to produce tyrosol from tyrosine. Glucosyltransferases from different resources were tested for ideal production of salidroside in the yeast. Metabolic flux was enhanced toward tyrosine biosynthesis by overexpressing pathway genes and eliminating feedback inhibition. The pathway genes were integrated into yeast chromosome, leading to a recombinant strain that produced 239.5 mg/L salidroside and 965.4 mg/L tyrosol. The production of salidroside and tyrosol reached up to 732.5 and 1394.6 mg/L, respectively, by fed-batch fermentation. Our work provides an alternative way for industrial large-scale production of salidroside and tyrosol from S. cerevisiae.

The role of cyclodextrins in ORAC-fluorescence assays. antioxidant capacity of tyrosol and caffeic acid with hydroxypropyl-β-cyclodextrin.

PubMed

García-Padial, Marcos; Martínez-Ohárriz, María Cristina; Navarro-Blasco, Iñigo; Zornoza, Arantza

2013-12-18

Tyrosol and caffeic acid are biophenols that contribute to the beneficial properties of virgin olive oil. The influence of hydroxypropyl-β-cyclodextrin (HPβ-CD) on their respective antioxidant capacities was analyzed. The ORAC antioxidant activity of tyrosol (expressed as μM Trolox equivalents/μM Tyrosol) was 0.83 ± 0.03 and it increased up to 1.20 ± 0.11 in the presence of 0.8 mM HPβ-CD. However, the ORAC antioxidant activity of caffeic acid experienced no change. The different effect of HPβ-CD on each compound was discussed. In addition, the effect of increasing concentrations of different cyclodextrins in the development of ORAC-fluorescence (ORAC-FL) assays was studied. The ORAC signal was higher for HPβ-CD, followed by Mβ-CD, β-CD, γ-CD and finally α-CD. These results could be explained by the formation of inclusion complexes with fluorescein.

Chemical characterization of a variety of cold-pressed gourmet oils available on the Brazilian market.

PubMed

Cicero, Nicola; Albergamo, Ambrogina; Salvo, Andrea; Bua, Giuseppe Daniel; Bartolomeo, Giovanni; Mangano, Valentina; Rotondo, Archimede; Di Stefano, Vita; Di Bella, Giuseppa; Dugo, Giacomo

2018-07-01

Different specialty extra virgin oils, produced by cold-pressing fruits/nuts (olive, pequi, palm, avocado, coconut, macadamia and Brazil nut) and seeds (grapeseed and canola), and retailed in the Brazilian region of Minas Gerais, were chemically characterized. Specifically, for each type of oil, the fatty acid composition was elucidated by GC-FID, the contents of selected polyphenols and squalene were determined respectively by UHPLC-MS and UHPLC-PDA, whereas minerals were explored by means of ICP-MS. Olive oil was confirmed to have the highest MUFA content due to a valuable level of oleic acid, while oils from grapeseed, Brazil nut and canola were marked by nutritionally important PUFA levels. The highest SFA content found in coconut oil was mainly due to the high levels of lauric acid, known for its advantageous HDL-raising effects. As for polyphenols, gourmet oils from palm, coconut and canola showed higher levels of phenolic acids (e.g. p-hydroxybenzoic, ferulic, syringic, acids) than olive oil, which was though characterized by peculiar antioxidants, such as tyrosol and hydroxytyrosol. Also, olive oil had the highest amount of squalene, followed by the oil from Brazil nut. Finally, all the investigated oils had very low levels (order of μg/kg) of pro-oxidant elements, such as Cu, Fe and Mn. Overall, these findings may fill the gaps still present in literature on certain compositional aspects of commercially available gourmet oils. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oleuropein attenuates cognitive dysfunction and oxidative stress induced by some anesthetic drugs in the hippocampal area of rats.

PubMed

Alirezaei, Masoud; Rezaei, Maryam; Hajighahramani, Shahin; Sookhtehzari, Ali; Kiani, Katayoun

2017-01-01

The present study was designed to evaluate the antioxidant effects of oleuropein against oxidative stress in the hippocampal area of rats. We used seven experimental groups as follows: Control, Propofol, Propofol-Ketamine (Pro.-Ket.), Xylazine-Ketamine (Xyl.-Ket.), and three oleuropein-pretreated groups (Ole.-Pro., Ole.-Pro.-Ket. and Ole.-Xyl.-Ket.). The oleuropein-pretreated groups received oleuropein (15 mg/kg body weight as orally) for 10 consecutive days. Propofol 100 mg/kg, xylazine 3 mg/kg, and ketamine 75 mg/kg once as ip was used on the 11th day of treatment. Spatial memory impairment and antioxidant status of hippocampus were measured via Morris water maze, lipid peroxidation marker, and antioxidant enzyme activities. Spatial memory impairment and lipid peroxidation significantly increased in Xyl.-Ket.-treated rats in comparison to the control, propofol, Ole.-Pro. and Ole.-Pro.-Ket. groups. Oleuropein pretreatment significantly reversed spatial memory impairment and lipid peroxidation in the Ole.-Xyl.-Ket. group as compared to the Xyl.-Ket.-treated rats. There was no significant difference between the control and the propofol group in lipid peroxidation and spatial memory status. Superoxide dismutase and catalase activities both significantly decreased in Xyl.-Ket.-treated rats when compared to the control, propofol, Ole.-Pro., Ole.-Pro.-Ket., and Ole.-Xyl.-Ket. groups. In contrast, glutathione peroxidase activity in Xyl.-Ket.-treated rats significantly increased as compared to the control, propofol, Pro.-Ket., Ole.-Pro., and Ole.-Pro.-Ket. groups. We concluded that xylazine in combination with ketamine is an oxidative anesthetic drug and oleuropein pretreatment attenuates cognitive dysfunction and oxidative stress induced by anesthesia in the hippocampal area of rats. We also confirmed the antioxidant properties of propofol as a promising antioxidant anesthetic agent.

Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

PubMed

Pourkhodadad, Soheila; Alirezaei, Masoud; Moghaddasi, Mehrnoush; Ahmadvand, Hassan; Karami, Manizheh; Delfan, Bahram; Khanipour, Zahra

2016-09-01

Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 μg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

Identification and Characterization of the Iridoid Synthase Involved in Oleuropein Biosynthesis in Olive (Olea europaea) Fruits.

PubMed

Alagna, Fiammetta; Geu-Flores, Fernando; Kries, Hajo; Panara, Francesco; Baldoni, Luciana; O'Connor, Sarah E; Osbourn, Anne

2016-03-11

The secoiridoids are the main class of specialized metabolites present in olive (Olea europaea L.) fruit. In particular, the secoiridoid oleuropein strongly influences olive oil quality because of its bitterness, which is a desirable trait. In addition, oleuropein possesses a wide range of pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. In accordance, obtaining high oleuropein varieties is a main goal of molecular breeding programs. Here we use a transcriptomic approach to identify candidate genes belonging to the secoiridoid pathway in olive. From these candidates, we have functionally characterized the olive homologue of iridoid synthase (OeISY), an unusual terpene cyclase that couples an NAD (P)H-dependent 1,4-reduction step with a subsequent cyclization, and we provide evidence that OeISY likely generates the monoterpene scaffold of oleuropein in olive fruits. OeISY, the first pathway gene characterized for this type of secoiridoid, is a potential target for breeding programs in a high value secoiridoid-accumulating species. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Synergistic effect of amphotericin B and tyrosol on biofilm formed by Candida krusei and Candida tropicalis from intrauterine device users.

PubMed

Shanmughapriya, Santhanam; Sornakumari, Haridevvenkatesan; Lency, Arumugam; Kavitha, Senthil; Natarajaseenivasan, Kalimuthusamy

2014-11-01

The presence of intrauterine contraceptive devices (IUDs) provides a solid surface for attachment of microorganisms and an ideal niche for the biofilm to form and flourish. Vaginal candidiasis is often associated with the use of IUDs. Treatment of vaginal candidiasis that develops in connection with IUD use requires their immediate removal. Here, we present in vitro evidence to support the use of combination therapy to inhibit Candida biofilm. Twenty-three clinical Candida isolates (10 C. krusei and 13 C. tropicalis) recovered from endocervical swabs obtained from IUD and non-IUD users were assessed for biofilm-formation ability. The rate of isolation of Candida did not differ significantly among IUD and non-IUD users (P = 0.183), but the biofilm-formation ability of isolates differed significantly (P = 0.02). An in vitro biofilm model with the obtained isolates was subjected to treatment with amphotericin B, tyrosol, and a combination of amphotericin B and tyrosol. Inhibition of biofilm by amphotericin B or tyrosol was found to be concentration dependent, with 50% reduction (P < 0.05) at 4 mg/l and 80 μM, respectively. Hence, a combination effect of tyrosol and amphotericin B was studied. Interestingly, approximately 90% reduction in biofilm was observed with use of 80 μM tyrosol combined with 4 mg/l amphotericin B (P < 0.001). This represents a first step in establishing an appropriate antibiofilm therapy when yeasts are present. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Removal of tyrosol from water by adsorption on carbonaceous materials and electrochemical advanced oxidation processes.

PubMed

Flores, Nelly; Sharif, Farbod; Yasri, Nael; Brillas, Enric; Sirés, Ignasi; Roberts, Edward P L

2018-06-01

This work compares the ability of physical and chemical treatments, namely adsorption and electrochemical advanced oxidation processes, to remove tyrosol from aqueous medium. Adsorption on graphene nanoplatelets (GNPs) performed much better than that with a graphite intercalation compound. Adsorption isotherms were found to follow the Freundlich model (R 2  = 0.96), which is characteristic of a chemisorption process. Successful electrochemical regeneration enables 5 successive adsorption/regeneration cycles before corrosion of GNPs occurs. Other typical aromatic contaminants that may coexist with tyrosol can be also adsorbed on GNPs. Percentage of regeneration efficiency of GNPs showed a higher affinity towards Lewis acids group compounds and a lower one towards Lewis base. The treatment of 100 mL of 0.723 mM tyrosol solutions in non-chlorinated and chlorinated matrices at pH 3.0 was carried out by electrochemical oxidation with electrogenerated H 2 O 2 (EO-H 2 O 2 ), electro-Fenton (EF) and UVA photoelectro-Fenton (PEF). Trials were made with a BDD anode and an air-diffusion cathode at 10-30 mA cm -2 . Hydroxyl radicals formed at the anode from water oxidation and/or in the bulk from Fenton's reaction between added Fe 2+ and generated H 2 O 2 , along with active chlorine produced in chlorinated medium, were the main oxidants. Tyrosol concentration always decayed following a pseudo-first-order kinetics and its mineralization rose as EO-H 2 O 2  < EF < PEF, more rapidly in the chlorinated matrix. The potent photolysis of intermediates under UVA radiation explained the almost total mineralization achieved by PEF in the latter medium. The effect of current density and tyrosol content on the performance of all processes was examined. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antiarrhythmic activity of n-tyrosol during acute myocardial ischemia and reperfusion.

PubMed

Chernyshova, G A; Plotnikov, M B; Smol'yakova, V I; Golubeva, I V; Aliev, O I; Tolstikova, T G; Krysin, A P; Sorokina, I V

2007-06-01

Antiarrhythmic activity of n-tyrosol was demonstrated on the model of early occlusion and reperfusion arrhythmia. The preparation reduces the incidence of ventricular tachycardia and fibrillation, increases the percent of animals without ventricular arrhythmia, and moderates the severity of developing ventricular arrhythmias.

Simultaneous separation and purification of flavonoids and oleuropein from Olea europaea L. (olive) leaves using macroporous resin.

PubMed

Li, Chen; Zheng, Yuanyuan; Wang, Xiaofei; Feng, Shilan; Di, Duolong

2011-12-01

This study developed a feasible process to simultaneously separate and purify polyphenols, including flavonoids and oleuropein, from the leaves of Olea europaea L. Macroporous resins were used as the separation and purification materials. The performance and separation capabilities of eight resins (D101, DM130, HPD450, LSA-21, LSA-40, 07C, LSD001 and HPD600) were systematically evaluated. The contents of target polyphenols in different extracts were determined using ultraviolet (for flavonoids) and high-performance liquid chromatographic (for oleuropein) methods. The static adsorption and desorption results showed that resin LSA-21 had better adsorption properties among the eight resins. Influential factors such as extraction method, pH value of feeding solution, desorption solution, adsorption kinetics and adsorption isotherm, etc. to the extraction and purification of these polyphenols were successively investigated on resin LSA-21. The target flavonoids and oleuropein were selectively purified using resin LSA-21. Compared with the contents in raw leaves, the contents of total flavonoids and oleuropein in the final purified products were increased 13.2-fold (from 16 to 211 g kg(-1) ) and 7.5-fold (from 120 to 902 g kg(-1) ) with recovery yields of 87.9% and 85.6%, respectively. This extraction and purification method could be used in the large-scale enrichment or purification of flavonoids, oleuropein and other polyphenols from O. europaea L. leaves or other herbal materials in industrial, food processing and medical manufacture. Copyright © 2011 Society of Chemical Industry.

Potential Therapeutic Effects of Oleuropein Aglycone in Alzheimer's Disease.

PubMed

Martorell, Miquel; Forman, Katherine; Castro, Natalia; Capó, Xavier; Tejada, Silvia; Sureda, Antoni

Alzheimer's disease (AD) is an age-associated neurodegenerative amyloid disease and is considered a social and clinical problem the last decades, particularly in the Western countries. Amyloid diseases are characterized by the deposition of typically aggregated protein/peptides in tissues that are associated with brain degeneration and progressive cognitive impairment. The amyloid plaques and neurofibrillary tangles arise as a result of self-assembly into fibrillar material of amyloid-β protein and hyperphosphorylated tau, respectively. Moreover, mounting evidence shows that oxidative and nitrosative stress plays a central role in the pathogenesis of neurodegenerative disorders such as AD. Oleuropein belongs to a specific group of polyphenols, the secoiridoids, which are abundant in Oleaceae. Oleuropein aglycone is abundant in extra virgin olive oil and it is generated as a product of a glucosidase released when olive fruits are crushed. This secoiridoid compound has radical-scavenging activity and antioxidative effects and it is considered a promising target to prevent amyloid toxicity as an inhibitor of the oligomer nucleation and growth. The neuroprotective and antioxidant effects of flavonoids have been found to strongly depend on their structure and functional groups. Oleuropein aglycone counteracts amyloid aggregation and toxicity affecting different pathways: amyloid precursor protein processing, amyloid-β peptide and tau aggregation, autophagy impairment, and neuroinflammation. In the current work, available literature on oleuropein aglycone effects as antioxidant and inhibitor of amyloid deposits in AD is reviewed. Moreover, we discuss the chemistry, food sources and bioavailability of oleuropein aglycone.

Employment of High-Performance Thin-Layer Chromatography for the Quantification of Oleuropein in Olive Leaves and the Selection of a Suitable Solvent System for Its Isolation with Centrifugal Partition Chromatography.

PubMed

Boka, Vasiliki-Ioanna; Argyropoulou, Aikaterini; Gikas, Evangelos; Angelis, Apostolis; Aligiannis, Nektarios; Skaltsounis, Alexios-Leandros

2015-11-01

A high-performance thin-layer chromatographic methodology was developed and validated for the isolation and quantitative determination of oleuropein in two extracts of Olea europaea leaves. OLE_A was a crude acetone extract, while OLE_AA was its defatted residue. Initially, high-performance thin-layer chromatography was employed for the purification process of oleuropein with fast centrifugal partition chromatography, replacing high-performance liquid-chromatography, in the stage of the determination of the distribution coefficient and the retention volume. A densitometric method was developed for the determination of the distribution coefficients, KC = CS/CM. The total concentrations of the target compound in the stationary phase (CS) and in the mobile phase (CM) were calculated by the area measured in the high-performance thin-layer chromatogram. The estimated Kc was also used for the calculation of the retention volume, VR, with a chromatographic retention equation. The obtained data were successfully applied for the purification of oleuropein and the experimental results confirmed the theoretical predictions, indicating that high-performance thin-layer chromatography could be an important counterpart in the phytochemical study of natural products. The isolated oleuropein (purity > 95%) was subsequently used for the estimation of its content in each extract with a simple, sensitive and accurate high-performance thin-layer chromatography method. The best fit calibration curve from 1.0 µg/track to 6.0 µg/track of oleuropein was polynomial and the quantification was achieved by UV detection at λ 240 nm. The method was validated giving rise to an efficient and high-throughput procedure, with the relative standard deviation % of repeatability and intermediate precision not exceeding 4.9% and accuracy between 92% and 98% (recovery rates). Moreover, the method was validated for robustness, limit of quantitation, and limit of detection. The amount of oleuropein for OLE_A, OLE_AA, and an aqueous extract of olive leaves was estimated to be 35.5% ± 2.7, 51.5% ± 1.4, and 12.5% ± 0.12, respectively. Statistical analysis proved that the method is repeatable and selective, and can be effectively applied for the estimation of oleuropein in olive leaves' extracts, and could potentially replace high-performance liquid chromatography methodologies developed so far. Thus, the phytochemical investigation of oleuropein could be based on high-performance thin-layer chromatography coupled with separation processes, such as fast centrifugal partition chromatography, showing efficacy and credibility. Georg Thieme Verlag KG Stuttgart · New York.

Controlled release of tyrosol and ferulic acid encapsulated in chitosan-gelatin films after electron beam irradiation

NASA Astrophysics Data System (ADS)

Benbettaïeb, Nasreddine; Assifaoui, Ali; Karbowiak, Thomas; Debeaufort, Frédéric; Chambin, Odile

2016-01-01

This work deals with the study of the release kinetics of antioxidants (ferulic acid and tyrosol) incorporated into chitosan-gelatin edible films after irradiation processes. The aim was to determine the influence of electron beam irradiation (at 60 kGy) on the retention of antioxidants in the film, their release in water (pH=7) at 25 °C, in relation with the barrier and mechanical properties of biopolymer films. The film preparation process coupled to the irradiation induced a loss of about 20% of tyrosol but did not affect the ferulic acid content. However, 27% of the ferulic acid remained entrapped in the biopolymer network during the release experiments whereas all tyrosol was released. Irradiation induced a reduction of the release rate for both compounds, revealing that cross-linking occurred during irradiation. This was confirmed by the mechanical properties enhancement which tensile strength value significantly increased and by the reduction of permeabilities. Although molecular weights, molar volume and molecular radius of the two compounds are very similar, the effective diffusivity of tyrosol was 40 times greater than that of ferulic acid. The much lower effective diffusion coefficient of ferulic acid as determined from the release kinetics was explained by the interactions settled between ferulic acid molecules and the gelatin-chitosan matrix. As expected, the electron beam irradiation allowed modulating the retention and then the release of antioxidants encapsulated.

Antihyperglycemic effect of thymoquinone and oleuropein, on streptozotocin-induced diabetes mellitus in experimental animals

PubMed Central

Sangi, Sibghatullah Muhammad Ali; Sulaiman, Mansour Ibrahim; El-wahab, Mohammed Fawzy Abd; Ahmedani, Elsamoual Ibrahim; Ali, Soad Shaker

2015-01-01

Background: Diabetes mellitus is one of the most important diseases related with endocrines. Its main manifestation includes abnormal metabolism of carbohydrates and lipids and inappropriate hyperglycemia that is caused by absolute or relative insulin deficiency. It affects humankind worldwide. Objectives: Our research was aimed to observe antihyperglycemic activity of thymoquinone and oleuropein. Materials and Methods: In this study, rats were divided into six groups, 6 rats in each. Diabetes was inducted by streptozotocin (STZ). The level of fasting blood glucose was determined for each rats during the experiment, doses of thymoquinone and oleuropein (3 mg/kg and 5 mg/kg) for both, were injected intraperitoneal. Pancreatic tissues were investigated to compare β-cells in diabetic and treated rats. Result and Conclusion: It was found that thymoquinone and oleuropein significantly decrease serum Glucose levels in STZ induced diabetic rats. PMID:26664013

Effect of zinc formulations, sodium chloride, and hydroxytyrosol on the growth/no-growth boundaries of table olive related yeasts.

PubMed

Romero-Gil, V; Rejano-Zapata, L; Garrido-Fernández, A; Arroyo-López, F N

2016-08-01

This study uses a mathematical approach to assessing the inhibitory effect of Zn(2)(+)(0-10 mM, obtained from ZnCl2 and ZnSO4) in presence of NaCl (0-8%) and hydroxytyrosol (0-2588 mg/L), on a yeast cocktail formed by species Pichia galeiformis, Pichia kudriavzevii, Pichia manshurica and Candida thaimueangensis obtained from spoilt green olive packages. The logistic/probabilistic models were built in laboratory medium using a total of 1980 responses (1188 for NaCl and 792 for hydroxytyrosol). ZnCl2 showed significantly higher inhibitory effect than ZnSO4 in the presence of both NaCl (p < 0.033) and hydroxytyrosol (p < 0.009). NaCl did not interfere the effect of Zn(2)(+)while hydroxytyrosol, at high levels, had a slight antagonistic effect. According to models, Zn(2)(+)inhibits (p = 0.01) the yeast cocktail in the range 4.5-5.0 mM for ZnCl2, or 8.5-9.5 mM for ZnSO4. Therefore, this work confirms the fungicidal activity of zinc compounds (mainly ZnCl2) in synthetic medium, and also shows that the loss of zinc effectiveness in real green Spanish-style olive packaging is not due to the presence of NaCl or hydroxytyrosol, two of the most abundant chemical compounds in the product. Copyright © 2016 Elsevier Ltd. All rights reserved.

The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology.

PubMed

Grossi, Cristina; Rigacci, Stefania; Ambrosini, Stefano; Ed Dami, Teresa; Luccarini, Ilaria; Traini, Chiara; Failli, Paola; Berti, Andrea; Casamenti, Fiorella; Stefani, Massimo

2013-01-01

The claimed beneficial effects of the Mediterranean diet include prevention of several age-related dysfunctions including neurodegenerative diseases and Alzheimer-like pathology. These effects have been related to the protection against cognitive decline associated with aging and disease by a number of polyphenols found in red wine and extra virgin olive oil. The double transgenic TgCRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 1.5 and 4, and age-matched wild type control mice were used to examine in vivo the effects of 8 weeks dietary supplementation of oleuropein aglycone (50 mg/kg of diet), the main polyphenol found in extra virgin olive oil. We report here that dietary supplementation of oleuropein aglycone strongly improves the cognitive performance of young/middle-aged TgCRND8 mice, a model of amyloid-ß deposition, respect to age-matched littermates with un-supplemented diet. Immunofluorescence analysis of cerebral tissue in oleuropein aglycone-fed transgenic mice showed remarkably reduced ß-amyloid levels and plaque deposits, which appeared less compact and "fluffy"; moreover, microglia migration to the plaques for phagocytosis and a remarkable reduction of the astrocyte reaction were evident. Finally, oleuropein aglycone-fed mice brain displayed an astonishingly intense autophagic reaction, as shown by the increase of autophagic markers expression and of lysosomal activity. Data obtained with cultured cells confirmed the latter evidence, suggesting mTOR regulation by oleuropein aglycone. Our results support, and provide mechanistic insights into, the beneficial effects against Alzheimer-associated neurodegeneration of a polyphenol enriched in the extra virgin olive oil, a major component of the Mediterranean diet.

Retention and distribution of polyphenols after pan-frying of French fries in oils enriched with olive leaf extract.

PubMed

Chiou, A; Salta, F N; Kalogeropoulos, N; Mylona, A; Ntalla, I; Andrikopoulos, N K

2007-10-01

Palm oil, olive oil, and sunflower oil were supplemented with an extract rich in polyphenols obtained from olive tree (Olea europaea) leaves at levels of 120 and 240 mg total polyphenols per kilogram of oil. Pan-frying of potatoes was performed in both the enriched and the nonsupplemented oils under domestic frying conditions. Total polyphenol content was estimated by the Folin-Ciocalteau assay, oleuropein was determined by HPLC analysis, while other individual polyphenols by GC/MS analysis. Fourteen polyphenol species were identified in the olive leaf extract, among which oleuropein predominated (1.25 g/kg olive leaves). All the enriched oils contained oleuropein before and after frying. Oleuropein as well as other polyphenol species were detected in all French fries cooked in enriched oils. Polyphenol intake by consuming French fries pan-fried in the enriched oils was calculated to be 6 to 31 times higher than that in the case of French fries fried in commercial oils, being dependent on the frying oil type.

Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic DSS colitis model.

PubMed

Sánchez-Fidalgo, Susana; Sánchez de Ibargüen, L; Cárdeno, A; Alarcón de la Lastra, C

2012-06-01

Recent epidemiological studies have shown that habitual consumption of extra virgin olive oil (EVOO), the characteristic culinary fat of the Mediterranean area, is effective in the prevention of diverse types of digestive disorders such as inflammatory bowel disease. Many of these benefits are, in addition to its high proportion of oleic acid, due to the high content of phenolic compounds. Six-week-old mice were randomized into three dietary groups: standard, EVOO and hydroxytyrosol-enriched EVOO. After 30 days, mice that were exposed to 3% DSS for 5 days developed acute colitis that progressed to severe chronic inflammation during a regime of 21 days of water. Diets enriched with EVOO significantly attenuated the clinical and histological signs of damage, improving results from disease activity index and reducing about 50% the mortality caused by DSS. Moreover, hydroxytyrosol supplement showed better results. Cytokines study showed that TNF-α was maintained near to sham control and IL-10 levels were significantly improved in EVOO and EVOO plus hydroxytyrosol diet-DSS groups. In the same way, COX-2 and iNOS were downregulated, and the activation of p38 MAPK was reduced. We also observed a higher significant reduction in iNOS in hydroxytyrosol-enriched EVOO compared with EVOO alone. EVOO diets exerted a noteworthy beneficial effect in chronic DSS-induced colitis by cytokine modulation and COX-2 and iNOS reduction via downregulation of p38 MAPK. In addition to the beneficial effect by EVOO, supplementation of the diet with hydroxytyrosol may improve chronic colitis through iNOS downregulation plus its antioxidant capacity.

Pencil graphite electrodes for improved electrochemical detection of oleuropein by the combination of Natural Deep Eutectic Solvents and graphene oxide.

PubMed

Gomez, Federico J V; Spisso, Adrian; Fernanda Silva, María

2017-11-01

A novel methodology is presented for the enhanced electrochemical detection of oleuropein in complex plant matrices by Graphene Oxide Pencil Grahite Electrode (GOPGE) in combination with a buffer modified with a Natural Deep Eutectic Solvent, containing 10% (v/v) of Lactic acid, Glucose and H 2 O (LGH). The electrochemical behavior of oleuropein in the modified-working buffer was examined using differential pulse voltammetry. The combination of both modifications, NADES modified buffer and nanomaterial modified electrode, LGH-GOPGE, resulted on a signal enhancement of 5.3 times higher than the bare electrode with unmodified buffer. A calibration curve of oleuropein was performed between 0.10 to 37 μM and a good linearity was obtained with a correlation coefficient of 0.989. Detection and quantification limits of the method were obtained as 30 and 102 nM, respectively. In addition, precision studies indicated that the voltammetric method was sufficiently repeatable, %RSD 0.01 and 3.16 (n = 5) for potential and intensity, respectively. Finally, the proposed electrochemical sensor was successfully applied to the determination of oleuropein in an olive leaf extract prepared by ultrasound-assisted extraction. The results obtained with the proposed electrochemical sensor were compared with Capillary Zone Electrophoresis analysis with satisfactory results. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The paradoxical effect of extra-virgin olive oil on oxidative phenomena during in vitro co-digestion with meat.

PubMed

Martini, Serena; Cavalchi, Martina; Conte, Angela; Tagliazucchi, Davide

2018-07-01

Extra-virgin olive oil is an integral part of the Mediterranean diet and its consumption has been associated with a reduction risk of chronic diseases. Here we tested the potential of extra-virgin olive oil to limit the oxidative phenomena during in vitro gastro-intestinal co-digestion with turkey breast meat. The extra-virgin olive oil was particularly rich in oleuropein aglycone isomers, which represented the 66.8% of total phenolic determined with MS/MS experiments. Meals supplemented with extra-virgin olive oil equivocally affected lipid peroxidation. At low concentration (2.5% respect to meat), a significant inhibition of lipid oxidation was observed, whereas lipid peroxidation was greatly enhanced when the amount of extra-virgin olive oil was increased in the gastro-intestinal system. The inhibitory effect observed at 2.5% extra-virgin olive oil was due to the antioxidant properties of extra-virgin olive oil phenolic compounds. At high concentration, extra-virgin olive oil phenolic compounds (especially hydroxytyrosol-derivative) behaved as pro-oxidants increasing the generation of lipid hydroperoxides from meat. At the same time, the presence in the digestive system of catalysers from meat induced the peroxidation of extra-virgin olive oil fatty acids, which was further intensified by the pro-oxidant activity of extra-virgin olive oil phenolic compounds. Our study underlined the importance of the timing and amount of consumption of extra-virgin olive oil as well as its phenolic composition in limiting the peroxidative phenomena on meat lipids during digestion. Copyright © 2018 Elsevier Ltd. All rights reserved.

Application of dried blood spot cards to determine olive oil phenols (hydroxytyrosol metabolites) in human blood.

PubMed

de Las Hazas, María Carmen López; Motilva, Maria José; Piñol, Carme; Macià, Alba

2016-10-01

In this study, a fast and simple blood sampling and sample pre-treatment method based on the use of the dried blood spot (DBS) cards and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for the quantification of olive oil phenolic metabolites in human blood was developed and validated. After validation, the method was applied to determine hydroxytyrosol metabolites in human blood samples after the acute intake of an olive oil phenolic extract. Using the FTA DMPK-A DBS card under optimum conditions, with 20µL as the blood solution volume, 100µL of methanol/Milli-Q water (50/50, v/v) as the extraction solvent and 7 disks punched out from the card, the main hydroxytyrosol metabolites (hydroxytyrosol-3-O-sulphate and hydroxytyrosol acetate sulphate) were identified and quantified. The developed methodology allowed detecting and quantifying the generated metabolites at low μM levels. The proposed method is a significant improvement over existing methods to determine phenolic metabolites circulating in blood and plasma samples, thus making blood sampling possible with the volunteer pricking their own finger, and the subsequent storage of the blood in the DBS cards prior to chromatographic analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Hydroxytyrosol and Potential Uses in Cardiovascular Diseases, Cancer, and AIDS

PubMed Central

Vilaplana-Pérez, Cristina; Auñón, David; García-Flores, Libia A.; Gil-Izquierdo, Angel

2014-01-01

Hydroxytyrosol is one of the main phenolic components of olive oil. It is present in the fruit and leaf of the olive (Olea europaea L.). During the past decades, it has been well documented that this phenolic compound has health benefits and a protective action has been found in preclinical studies against several diseases. Here, we review its bioavailability in human beings and several assays showing significant results related with cardiovascular diseases, cancer, and acquired immunodeficiency syndrome (AIDS). Mechanisms of action include potent anti-oxidant and anti-inflammatory effects, among others. The importance of hydroxytyrosol in protection of low-density lipoproteins and consequently its implication in the reduction of cardiovascular disease risk has been highlighted by the European Food Safety Authority, concluding that 5 mg of hydroxytyrosol and its derivatives should be consumed daily to reach this effect at physiological level. We discuss the potential uses of this compound in supplements, nutraceutic foods, or topical formulations in the disease risk reduction. Finally, we conclude that more studies are needed to sustain or reject many other health claims not yet fully documented and to validate these newly available hydroxytyrosol-based products, because it seems to be a good candidate to reduce the risk of diseases mentioned. PMID:25988120

A systems biology approach to investigate the antimicrobial activity of oleuropein

USDA-ARS?s Scientific Manuscript database

Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by ole...

[Antioxidant and cardioprotective effects of N-tyrosol in myocardial ischemia with reperfusion in rats].

PubMed

Smol'iakova, V I; Chernyshova, G A; Plotnikov, M B; Aliev, O I; Krasnov, E A

2010-01-01

We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.

Synthesis of deuterium-labelled substrates for the study of oleuropein biosynthesis in Olea europaea callus cultures.

PubMed

Serrilli, Anna Maria; Maggi, Agnese; Casagrande, Valentina; Bianco, Armandodoriano

2016-01-01

We propose the cell culture approach to investigate oleuropein (1) biogenesis in Olea europaea L. We suggest employing olive callus cultures to identify the iridoidic precursor of oleuropein. In fact, we confirmed that callus cells from olive shoot explants are able to produce key secoiridoid as 1. To enable this approach, we synthesised and characterised deuterium-labelled iridoidic precursors belonging both to the loganin and the 8-epiloganin series. These iridoids are [7,8-(2)H2]-7-deoxy-8-epi-loganin (2(D)), [8,10-(2)H2]-8-epi-loganin (4(D)) and [7,8-(2)H2]-7-deoxy-loganin (3(D)).

Olive polyphenol effects in a mouse model of chronic ethanol addiction.

PubMed

Carito, Valentina; Ceccanti, Mauro; Cestari, Vincenzo; Natella, Fausta; Bello, Cristiano; Coccurello, Roberto; Mancinelli, Rosanna; Fiore, Marco

2017-01-01

Alcohol addiction elicits oxidative imbalance and it is well known that polyphenols possess antioxidant properties. We investigated whether or not polyphenols could confer a protective potential against alcohol-induced oxidative stress. We administered (per os) for two months 20 mg/kg of olive polyphenols containing mostly hydroxytyrosol in alcoholic adult male mice. Hydroxytyrosol metabolites as hydroxytyrosol sulfate 1 and hydroxytyrosol sulfate 2 were found in the serum of mice administered with polyphenols with the highest amount in animals treated with both polyphenols and alcohol. Oxidative stress was evaluated by FORT (free oxygen radical test) and FORD (free oxygen radical defense) tests. Alcoholic mice showed a worse oxidative status than nonalcoholic mice (higher FORT and lower FORD) but polyphenol supplementation partially counteracted the alcohol pro-oxidant effects, as evidenced by FORT. A better understanding of the antioxidant protection provided by polyphenols might be of primary interest for drug discovery and dietary-based prevention of the damage associated with chronic alcohol abuse. Copyright © 2016 Elsevier Inc. All rights reserved.

[Effect of andrographolide on quorum sensing and relevant virulence genes of Candida albicans].

PubMed

Yan, Yuan-yuan; Shi, Gao-xiang; Shao, Jing; Lu, Ke-qiao; Zhang, Meng-xiang; Wang, Tian-ming; Wang, Bin; Wang, Chang-zhong

2015-01-01

To investigate the effect of andrographolide (AG) on quroum sensing (QS) and relevant virulence genes of Candida albicans. Gas-chromatography-mass spectrometry (GC-MS) was applied to detect the changes in the content of farnesol and tyrosol in C. albicans intervened by AG. The real-time quantitative PCR (qRT-PCR) was adopted to inspect the expressions of relevant virulence genes such as CHK1, PBS2 and HOG1 regulated by QS. At 2 h after the growth of C. albican, the farnesol and tyrosol secretions reduced, without notable change after intervention with AG. The secretions were highest at 12 h and decreased at 24 h. After the intervention with different concentrations of AG, the farnesol content reduces, whereas tyrosol increased, indicating a dose-dependence, particularly with 1 000 mg x L(-1) AG. qRT-PCR revealed that 1 000 mg x L(-1) AG could down-regulate CHK1 by 2.375, 3.330 and 4.043 times and PBS2 by 2.010, 4.210 and 4.760 times, with no significant change in HOG1. AG could inhibit the farnesol secretion, promote the tyrosol secretion and down-regulate QS-related virulence genes CHK1 and PBS2 expressions.

Membrane-Filtered Olive Mill Wastewater: Quality Assessment of the Dried Phenolic-Rich Fraction.

PubMed

Sedej, Ivana; Milczarek, Rebecca; Wang, Selina C; Sheng, Runqi; de Jesús Avena-Bustillos, Roberto; Dao, Lan; Takeoka, Gary

2016-04-01

A current trend in olive mill wastewater (OMWW) management is to not only decrease environmental pollution but also to extract and utilize valuable by-products. Therefore, the objectives of this study were to explore different techniques for drying a phenolic-rich membrane filtration fraction of OMWW and compare the techniques in terms of the dried product quality and feasibility of the process. The OMWW from 2 (3-phase and 2-phase) California mills was subjected to a 2-step membrane filtration process using a novel vibratory system. The reverse osmosis retentate (RO-R) is a phenolic-rich coproduct stream, and the reverse osmosis permeate is a near-pure water stream that could be recycled into the milling process. Spray-, freeze-, and infrared-drying were applied to obtain solid material from the RO-R. Drying of the RO-R was made possible only with addition of 10% maltodextrin as a carrier. The total soluble phenolics in dried RO-R were in the range 0.15 to 0.58 mg gallic acid equivalents/g of dry weight for 2-phase RO-R, and 1.38 to 2.17 mg gallic acid equivalents/g of dry weight for the 3-phase RO-R. Spray-dried RO-R from 3-phase OMWW showed remarkable antioxidant activity. Protocatechuic acid, tyrosol, vanillic acid, and p-coumaric acid were quantified in all dried RO-R, whereas 3-hydroxytyrosol was found in 3-phase dried RO-R. This combination of separation and drying technologies helps to add value and shelf-stability to an olive oil by-product and increase environmental sustainability of its production. © 2016 Institute of Food Technologists®

Olive oil polyphenols: A quantitative method by high-performance liquid-chromatography-diode-array detection for their determination and the assessment of the related health claim.

PubMed

Ricciutelli, Massimo; Marconi, Shara; Boarelli, Maria Chiara; Caprioli, Giovanni; Sagratini, Gianni; Ballini, Roberto; Fiorini, Dennis

2017-01-20

In order to assess if an extra virgin olive oil (EVOO) can be acknowledged with the health claim related to olive oil polyphenols (Reg. EU n.432/2012), a new method to quantify these species in EVOO, by means of liquid-liquid extraction followed by HPLC-DAD/MS/MS of the hydroalcoholic extract, has been developed and validated. Different extraction procedures, different types of reverse-phase analytical columns (Synergi Polar, Spherisorb ODS2 and Kinetex) and eluents have been tested. The chromatographic column Synergi Polar (250×4.6mm, 4μm), never used before in this kind of application, provided the best results, with water and methanol/isopropanol (9/1) as eluents. The method allows the quantification of the phenolic alcohols tyrosol and hydroxytyrosol, the phenolic acids vanillic, p-coumaric and ferulic acids, secoiridoids derivatives, the lignans, pinoresinol and acetoxypinoresinol and the flavonoids luteolin and apigenin. The new method has been applied to 20 commercial EVOOs belonging to two different price range categories (3.78-5.80 euros/L and 9.5-25.80 euros/L) and 5 olive oils. The obtained results highlight that acetoxypinoresinol, ferulic acid, vanillic acid and the total non secoiridoid phenolic substances resulted to be significantly higher in HEVOOs than in LEVOOs (P=0.0026, 0.0217, 0.0092, 0.0003 respectively). For most of the samples analysed there is excellent agreement between the results obtained by applying the HPLC method adopted by the International Olive Council and the results obtained by applying the presented HPLC method. Results obtained by HPLC methods have been also compared with the ones obtained by the colorimetric Folin-Ciocalteu method. Copyright © 2016 Elsevier B.V. All rights reserved.

Elevated circulating LDL phenol levels in men who consumed virgin rather than refined olive oil are associated with less oxidation of plasma LDL.

PubMed

de la Torre-Carbot, Karina; Chávez-Servín, Jorge L; Jaúregui, Olga; Castellote, Ana I; Lamuela-Raventós, Rosa M; Nurmi, Tarja; Poulsen, Henrik E; Gaddi, Antonio V; Kaikkonen, Jari; Zunft, Hans-Franz; Kiesewetter, Holger; Fitó, Montserrat; Covas, María-Isabel; López-Sabater, M Carmen

2010-03-01

In human LDL, the bioactivity of olive oil phenols is determined by the in vivo disposition of the biological metabolites of these compounds. Here, we examined how the ingestion of 2 similar olive oils affected the content of the metabolic forms of olive oil phenols in LDL in men. The oils differed in phenol concentrations as follows: high (629 mg/L) for virgin olive oil (VOO) and null (0 mg/L) for refined olive oil (ROO). The study population consisted of a subsample from the EUROLIVE study and a randomized controlled, crossover design was used. Intervention periods lasted 3 wk and were preceded by a 2-wk washout period. The levels of LDL hydroxytyrosol monosulfate and homovanillic acid sulfate, but not of tyrosol sulfate, increased after VOO ingestion (P < 0.05), whereas the concentrations of circulating oxidation markers, including oxidized LDL (oxLDL), conjugated dienes, and hydroxy fatty acids, decreased (P < 0.05). The levels of LDL phenols and oxidation markers were not affected by ROO consumption. The relative increase in the 3 LDL phenols was greater when men consumed VOO than when they consumed ROO (P < 0.05), as was the relative decrease in plasma oxLDL (P = 0.001) and hydroxy fatty acids (P < 0.001). Plasma oxLDL concentrations were negatively correlated with the LDL phenol levels (r = -0.296; P = 0.013). Phenols in LDL were not associated with other oxidation markers. In summary, the phenol concentration of olive oil modulates the phenolic metabolite content in LDL after sustained, daily consumption. The inverse relationship of these metabolites with the degree of LDL oxidation supports the in vivo antioxidant role of olive oil phenolics compounds.

Simple quantification of phenolic compounds present in the minor fraction of virgin olive oil by LC-DAD-FLD.

PubMed

Godoy-Caballero, M P; Acedo-Valenzuela, M I; Galeano-Díaz, T

2012-11-15

This paper presents the results of the study on the extraction, identification and quantification of a group of important phenolic compounds in virgin olive oil (VOO) samples, obtained from olives of various varieties, by liquid chromatography coupled to UV-vis and fluorescence detection. Sixteen phenolic compounds belonging to different families have been identified and quantified spending a total time of 25 min. The linearity was examined by establishing the external standard calibration curves. Four order linear ranges and limits of detection ranging from 0.02 to 0.6 μg mL(-1) and 0.006 to 0.3 μg mL(-1) were achieved using UV-vis and fluorescence detection, respectively. Regarding the real samples, for the determination of the phenolic compounds in higher concentrations (hydroxytyrosol and tyrosol) a simple liquid-liquid extraction with ethanol was used to make the sample compatible with the mobile phase. Recovery values close to 100% were obtained. However, a previous solid phase extraction with Diol cartridges was necessary to concentrate and separate the minor phenolic compounds of the main interferences. The parameters affecting this step were carefully optimized and, after that, recoveries near 80-100% were obtained for the rest of the studied phenolic compounds. Also, the limits of detection were improved 15 times. Finally, the standard addition method was carried out for each of the analytes and no matrix effect was found, so the quantification of the 16 phenolic compounds from different monovarietal VOO was carried out by using the corresponding external standard calibration plot. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of simple, double and gelled double emulsions as hydroxytyrosol and n-3 fatty acid delivery systems.

PubMed

Flaiz, Linda; Freire, María; Cofrades, Susana; Mateos, Raquel; Weiss, Jochen; Jiménez-Colmenero, Francisco; Bou, Ricard

2016-12-15

The purpose of this study was to compare three different emulsion-based systems, namely simple emulsion, double emulsion and gelled double emulsion, for delivery of n-3 fatty acids (perilla oil at 300g/kg) and hydroxytyrosol (300mg/kg). Considering that their structural differences may affect their physical and oxidative stability, this was studied by storing them at 4°C for 22days in the dark. The results showed that the oxidative status was maintained in all systems by the addition of hydroxytyrosol. However, there was some loss of hydroxytyrosol, mainly during sample storage and during preparation of the gelled double emulsion. Moreover, the antioxidant loss was more pronounced in more compartmentalized systems, which was attributed to their increased surface area. However, the double emulsion was found to be less stable than the gelled emulsion. Overall, the encapsulation of labile compounds in more complex systems needs to be carefully studied and adapted to specific technological and/or nutritional requirements. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Solvent-Free Microwave-Assisted Extraction of Polyphenols from Olive Tree Leaves: Antioxidant and Antimicrobial Properties.

PubMed

Şahin, Selin; Samli, Ruya; Tan, Ayşe Seher Birteksöz; Barba, Francisco J; Chemat, Farid; Cravotto, Giancarlo; Lorenzo, José M

2017-06-24

Response surface methodology (RSM) and artificial neural networks (ANN) were evaluated and compared in order to decide which method was the most appropriate to predict and optimize total phenolic content (TPC) and oleuropein yields in olive tree leaf ( Olea europaea ) extracts, obtained after solvent-free microwave-assisted extraction (SFMAE). The SFMAE processing conditions were: microwave irradiation power 250-350 W, extraction time 2-3 min, and the amount of sample 5-10 g. Furthermore, the antioxidant and antimicrobial activities of the olive leaf extracts, obtained under optimal extraction conditions, were assessed by several in vitro assays. ANN had better prediction performance for TPC and oleuropein yields compared to RSM. The optimum extraction conditions to recover both TPC and oleuropein were: irradiation power 250 W, extraction time 2 min, and amount of sample 5 g, independent of the method used for prediction. Under these conditions, the maximal yield of oleuropein (0.060 ± 0.012 ppm) was obtained and the amount of TPC was 2.480 ± 0.060 ppm. Moreover, olive leaf extracts obtained under optimum SFMAE conditions showed antibacterial activity against S. aureus and S. epidermidis , with a minimum inhibitory concentration (MIC) value of 1.25 mg/mL.

Oleuropein and Cancer Chemoprevention: The Link is Hot.

PubMed

Ahmad Farooqi, Ammad; Fayyaz, Sundas; Silva, Ana Sanches; Sureda, Antoni; Nabavi, Seyed Fazel; Mocan, Andrei; Nabavi, Seyed Mohammad; Bishayee, Anupam

2017-04-29

Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed.

Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: a randomized, placebo-controlled, crossover trial.

PubMed

de Bock, Martin; Derraik, José G B; Brennan, Christine M; Biggs, Janene B; Morgan, Philip E; Hodgkinson, Steven C; Hofman, Paul L; Cutfield, Wayne S

2013-01-01

Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans. To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men. Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4 ± 5.5 years and BMI 28.0 ± 2.0 kg/m(2)) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function. Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome.

A novel liquid chromatography method using diode-array detector for the determination of oleuropein in dietary supplements.

PubMed

Bertolini, Tiziana; Vicentini, Lorenza; Boschetti, Silvia; Andreatta, Paolo; Gatti, Rita

2016-09-10

A simple and fast chromatographic method using ultraviolet diode-array detector (UV-DAD) was developed for the automatic high performance liquid chromatography (HPLC) determination of the title of oleuropein in a new dietary supplements in form of effervescent granules. The chromatographic separations were performed on a C18 core-shell column with detection at λ=232nm. The mobile phase consisted of deionized water with 0.1% TFA and acetonitrile under gradient conditions at a flow-rate of 0.8mL/min. Oleuropein and oleuroside present in the raw material were characterized by high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The validation of the analytical procedure has been performed determining the following parameters: specificity, linearity, repeatability, reproducibility, accuracy, limit of quantification (LOQ), stability of the standard and sample solutions. Linear response was observed in fortified placebo solutions (determination coefficient: 0.9998). Intra-day precision (relative standard deviation, RSD) was ≤5.0% for peak area and for retention times (tR) without significant differences between intra- and inter-day data. The limits of quantitation (LOQ) was about 5μg/mL and 9pmol/inject. Oleuropein recovery studies gave good results (99.9%) with a R.S.D. of 0.5%. The speed of analysis and the stability of the solutions with a fluctuation Δ (%) ≤2.0 at room temperature means an undoubted advantage of the method allowing the simultaneous preparation of many samples and consecutive chromatographic analyses by using an autosampler. The developed method is suitable for the quality control of oleuropein in raw material and industrial products. The method can be applied in any analytical laboratory not requiring a sophisticated instrumentation. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of natural antioxidants in cyclophosphamide-induced hepatotoxicity: Role of Nrf2/HO-1 pathway.

PubMed

Sherif, Iman O

2018-05-22

Hepatotoxicity induced by cyclophosphamide (Cyclo) is a major concern in clinical practice. This study was designed to investigate the possible cytoprotective effect of natural antioxidants as oleuropein and quercetin against Cyclo induced hepatotoxicity via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Male Wistar rats were randomly divided into six groups and treated for 10 days as follow: Group I (Normal control) received saline, group II (Oleu control): received orally oleuropein 30 mg/kg/day, group III (Quer control): administered orally quercetin 50 mg/kg/day, group IV (Cyclo): received saline and injected with single intraperitoneal (i.p) dose of Cyclo 200 mg/kg at day 5, group V (Oleu ttt): treated with oleuropein plus Cyclo i.p. injection at day 5, and group VI (Quer ttt): treated with quercetin plus Cyclo i.p. injection at day 5. Injection of Cyclo showed marked increase in serum transaminases and alkaline phosphatase, hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-⍺) levels along with significant reduction in hepatic reduced glutathione (GSH), superoxide dismutase (SOD), and catalase levels in addition to downregulation of hepatic Nrf2 and HO-1 expressions and reduction in hepatic nuclear Nrf2 binding activity when compared with normal group. Histopathological examination of Cyclo treated rats revealed hepatic damage. Both oleuropein and quercetin exhibited an improvement in the biochemical and histopathological findings. In conclusion, the natural antioxidants oleuropein and quercetin counteract the Cyclo induced hepatotoxicity through activation of Nrf2/HO-1 signaling pathway with subsequent suppression of oxidative stress and inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Mechanisms of action of phenolic compounds in olive.

PubMed

Rafehi, Haloom; Ververis, Katherine; Karagiannis, Tom C

2012-06-01

Olive oil, an oil rich in monounsaturated fatty acids (MUFCs) and minor constituents including phenolic compounds, is a major component of the Mediterranean diet. The potential health benefits of the Mediterranean diet were highlighted by the seminal Seven Countries Study, and more contemporary research has identified olive oil as a major element responsible for these effects. It is emerging that the phenolic compounds are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil (EVOO). In particular, the phenolic compound, hydroxytyrosol has been identified as one of the most potent antioxidants found in olive oil. This review will briefly consider historical aspects of olive oil research and the biological properties of phenolic compounds in olive oil will be discussed. The focus of the discussion will be related to the mechanisms of action of hydroxytyrosol. Studies have demonstrated that hydroxytyrosol induces apoptosis and cell cycle arrest in cancer cells. Further, research has shown that hydroxytyrosol can prevent cardiovascular disease by reducing the expression of adhesion molecules on endothelial cells and preventing the oxidation of low-density lipoprotein (LDL). The molecular mechanisms accounting for these effects are reviewed.

Production of salidroside in metabolically engineered Escherichia coli

PubMed Central

Bai, Yanfen; Bi, Huiping; Zhuang, Yibin; Liu, Chang; Cai, Tao; Liu, Xiaonan; Zhang, Xueli; Liu, Tao; Ma, Yanhe

2014-01-01

Salidroside (1) is the most important bioactive component of Rhodiola (also called as “Tibetan Ginseng”), which is a valuable medicinal herb exhibiting several adaptogenic properties. Due to the inefficiency of plant extraction and chemical synthesis, the supply of salidroside (1) is currently limited. Herein, we achieved unprecedented biosynthesis of salidroside (1) from glucose in a microorganism. First, the pyruvate decarboxylase ARO10 and endogenous alcohol dehydrogenases were recruited to convert 4-hydroxyphenylpyruvate (2), an intermediate of L-tyrosine pathway, to tyrosol (3) in Escherichia coli. Subsequently, tyrosol production was improved by overexpressing the pathway genes, and by eliminating competing pathways and feedback inhibition. Finally, by introducing Rhodiola-derived glycosyltransferase UGT73B6 into the above-mentioned recombinant strain, salidroside (1) was produced with a titer of 56.9 mg/L. Interestingly, the Rhodiola-derived glycosyltransferase, UGT73B6, also catalyzed the attachment of glucose to the phenol position of tyrosol (3) to form icariside D2 (4), which was not reported in any previous literatures. PMID:25323006

Isolation of a thermophilic and halophilic tyrosol-degrading Geobacillus from a Tunisian high-temperature oil field.

PubMed

Chamkha, Mohamed; Mnif, Sami; Sayadi, Sami

2008-06-01

An aerobic, thermophilic, halotolerant and Gram-positive bacterium, designated strain C5, was isolated from a high-temperature oil field, located in Sfax, Tunisia, after enrichment on tyrosol. Strain C5 grew between 25 and 70 degrees C and optimally at 50 degrees C. It grew in the presence of 0-12% (w/v) NaCl, with optimum growth at 3% (w/v) NaCl. Strain C5 was able to degrade tyrosol aerobically, in the presence of 30 g L(-1) NaCl and under warm conditions (55 degrees C). The degradation of tyrosol proceeded via p-hydroxyphenylacetic and 3,4-dihydroxyphenylacetic acids. The products were confirmed by HPLC and GC-MS analyses. Strain C5 was also found to degrde a wide range of other aromatic compounds, including benzoic, p-hydroxybenzoic, protocatechuic, vanillic, p-hydroxyphenylacetic, 3,4-dihydroxyphenylacetic, cinnamic and ferulic acids, phenol and m-cresol. Moreover, strain C5 was grown on diesel and crude oil as sole carbon and energy sources. Strain C5 was also able to utilize several carbohydrates. Phenotypic characteristics and phylogenetic analysis of the 16S rRNA gene sequence of strain C5 revealed that it was related to members of the genus Geobacillus, being most closely related to the type strain of G. pallidus (99% sequence similarity). In addition, we report on growth of the type strain of G. pallidus on different aromatic compounds and hydrocarbons.

Separation and identification of phenolic compounds of extra virgin olive oil from Olea europaea L. by HPLC-DAD-SPE-NMR/MS. Identification of a new diastereoisomer of the aldehydic form of oleuropein aglycone.

PubMed

Pérez-Trujillo, Míriam; Gómez-Caravaca, Ana María; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto; Parella, Teodor

2010-08-25

The phenolic fraction of a monovarietal extra virgin olive oil (EVOO) from Olea europaea L. var. Cornezuelo was studied by the hyphenated HPLC-DAD-SPE-NMR/MS techniques. This survey led to the identification of 25 main compounds. One was identified as a new diastereoisomer of the aldehydic form of oleuropein aglycone (AOA) and characterized by 1D and 2D NMR techniques. The relative configuration of this new AOA was determined as 5R*,8S*,9S* on the basis of the results obtained from the combination of NOE experiments and Monte Carlo conformational search calculations. Assuming, as for the described diastereoisomers, that the new AOA comes from the natural oleuropein aglycone (OA), the absolute configuration was proposed as 5S,8R,9R.

Inhibition of 6-hydroxydopamine-induced PC12 cell apoptosis by olive (Olea europaea L.) leaf extract is performed by its main component oleuropein.

PubMed

Pasban-Aliabadi, Hamzeh; Esmaeili-Mahani, Saeed; Sheibani, Vahid; Abbasnejad, Mehdi; Mehdizadeh, Anahita; Yaghoobi, Mohammad Mehdi

2013-04-01

Parkinson disease (PD) is the most common progressive neurodegenerative disorder characterized by progressive death of midbrain dopaminergic neurons. Most neurodegenerative disease treatments are, at present, palliative. However, some natural herbal products have been shown to rescue neurons from death and apoptosis in some of neurodegenerative diseases. Not only Olea europaea L. olive oil, but also the leaves of this plant have been used for medical purposes. Olive leaf extract (OLE) is being used by people as a drink across the world and as an integral ingredient in their desire to maintain and improve their health. Here, we investigated the effects of OLE and its main phenolic component oleuropein on 6-hydroxydopamine (6-OHDA)-induced toxicity in rat adrenal pheochromocytoma (PC12) cells as an in vitro model of PD. Cell damage was induced by 150 μM 6-OHDA. The cell survival rate was examined by MTT assay. Generation of intra-cellular reactive oxygen species (ROS) was studied using fluorescence spectrophotometry. Immunoblotting and DNA analysis were also employed to determine the levels of biochemical markers of apoptosis in the cells. The data showed that 6-OHDA could decrease the viability of the cells. In addition, intra-cellular ROS, activated caspase 3, Bax/Bcl-2 ratio, as well as DNA fragmentation were significantly increased in 6-OHDA-treated cells. Incubation of cells with OLE (400 and 600 μg/mL) and oleuropein (20 and 25 μg/mL) could decrease cell damage and reduce biochemical markers of cell death. The results suggest that OLE and oleuropein have anti-oxidant protective effects against 6-OHDA-induced PC12 cell damage. The protective effects of OLE and oleuropein are correlative with their anti-oxidative and anti-apoptotic properties and suggest their therapeutic potential in the treatment of PD.

Inhibition of mammalian DNA polymerases and the suppression of inflammatory and allergic responses by tyrosol from used activated charcoal waste generated during sake production.

PubMed

Mizushina, Yoshiyuki; Ogawa, Yoshiaki; Onodera, Takefumi; Kuriyama, Isoko; Sakamoto, Yuka; Nishikori, Shu; Kamisuki, Shinji; Sugawara, Fumio

2014-08-06

The components adsorbed onto activated charcoal following the fermentation process of the Japanese rice wine "sake" have been studied with the aim of identifying suitable applications for this industrial food waste product. The absorbed materials were effectively extracted from the charcoal, and inhibited the activity of several mammalian DNA polymerases (pols). Subsequent purification of the extract afforded tyrosol [4-(2-hydroxyethyl)phenol] as the active component, which selectively inhibited the activity of 11 mammalian pols with IC50 values in the range of 34.3-46.1 μM. In contrast, this compound did not influence the activities of plant or prokaryotic pols or any of the other DNA metabolic enzymes tested. Tyrosol suppressed both anti-inflammatory and antiallergic effects in vivo, including 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory mouse ear edema, and immunoglobulin E-induced passive cutaneous anaphylactic reaction in mice. These results suggested that this byproduct formed during the sake-brewing process could be used as an anti-inflammatory and/or antiallergic agent.

Phytochemical Characterization of an Adaptogenic Preparation from Rhodiola heterodonta

PubMed Central

Grace, Mary H.; Yousef, Gad G.; Kurmukov, Anvar G.; Raskin, Ilya; Lila, Mary Ann

2013-01-01

The phytochemical constituents of a biologically active, standardized, 80% ethanol extract of Rhodiola heterodonta were characterized. The extract was fractionated over a Sephadex LH-20 column to afford two main fractions representing two classes of secondary metabolites: phenylethanoids and proanthocyanidins. This fractionation facilitated the identification and quantification of individual compounds in the fractions and sub-fractions using HPLC, and LC-MS. The major compounds in the phenylethanoid fraction were heterodontoside, tyrosol methyl ether, salidroside, viridoside, mongrhoside, tyrosol, and the cyanogenic glucoside rhodiocyanoside A. These seven compounds comprised 17.4% of the EtOH extract. Proanthocyanidins ranged from oligomers to polymers based on epigallocatechin and gallate units. The main identified oligomeric compounds in the proanthocyanidin fraction were epigallocatechin gallate, epigallocatechin-epigallocatechin-3-O-gallate and 3-O-galloylepigallocatechin-epigallocatechin-3-O-gallate, which constituted 1.75% of the ethanol extract. Tyrosol methyl ether, mongrhoside, and the two proanthocyanidin dimers were reported for the first time from this species in this study. Intraperitoneal injection of the 80% ethanol extract increased survival time of mice under hypoxia by 192%, as an indication of adaptogenic activity. PMID:19768982

Polyphenols benefits of olive leaf (Olea europaea L) to human health.

PubMed

Vogel, Patrícia; Kasper Machado, Isabel; Garavaglia, Juliano; Zani, Valdeni Terezinha; de Souza, Daiana; Morelo Dal Bosco, Simone

2014-12-17

The phenolic compounds present in olive leaves (Olea europaea L.) confer benefits to the human health. To review the scientific literature about the benefits of the polyphenols of olive leaves to human health. Literature review in the LILACS-BIREME, SciELO and MEDLINE databases for publications in English, Portuguese and Spanish with the descriptors "Olea europaea", "olive leaves", "olive leaf", "olive leaves extracts", "olive leaf extracts", "phenolic compounds", "polyphenols", "oleuropein", "chemical composition", and "health". There were identified 92 articles, but only 38 related to the objectives of the study and 9 articles cited in the works were included due to their relevance. The phenolic compounds present in olive leaves, especially the oleuropein, are associated to antioxidant, antihypertensive, hypoglycemic, hypocholesterolemic and cardioprotective activity. Furthermore, studies associate the oleuropein to an anti-inflammatory effect in trauma of the bone marrow and as a support in the treatment of obesity. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Kinetic improvement of olive leaves' bioactive compounds extraction by using power ultrasound in a wide temperature range.

PubMed

Khemakhem, Ibtihel; Ahmad-Qasem, Margarita Hussam; Catalán, Enrique Barrajón; Micol, Vicente; García-Pérez, Jose Vicente; Ayadi, Mohamed Ali; Bouaziz, Mohamed

2017-01-01

In this study, the effect of temperature and ultrasonic application on extraction kinetics of polyphenols from dried olive leaf was investigated. Conventional (CVE) and ultrasonic-assisted extraction (UAE) were performed at 10, 20, 30, 50 and 70°C using water as solvent. Extracts were characterized by measuring the total phenolic content, the antioxidant capacity and the oleuropein content (HPLC-DAD/MS-MS). Moreover, Naik's model was used to mathematically describe the extraction kinetics. The experimental results showed that phenolic extraction was faster in UAE (ultrasonic-assisted extraction) than in CVE (conventional extraction), being extraction kinetics satisfactorily described using Naik model (include VAR>98%). Besides, the total phenolic content, the antioxidant capacity and the oleuropein content were significantly (p<0.05) improved by increasing the temperature in both CVE and UAE. Oleuropein content reached 6.57±0.18 being extracted approximately 88% in the first minute for UAE experiments. Copyright © 2016 Elsevier B.V. All rights reserved.

Polyphenolic profile as a useful tool to identify the wood used in wine aging.

PubMed

Sanz, Miriam; Fernández de Simón, Brígida; Cadahía, Estrella; Esteruelas, Enrique; Muñoz, Angel Ma; Hernández, Ma Teresa; Estrella, Isabel

2012-06-30

Although oak wood is the main material used in cooperage, other species are being considered as possible sources of wood for the production of wines and their derived products. In this work we have compared the phenolic composition of acacia (Robinia pseudoacacia), chestnut (Castanea sativa), cherry (Prunus avium) and ash (Fraxinus excelsior and F. americana) heartwoods, by using HPLC-DAD/ESI-MS/MS (some of these data have been showed in previous paper), as well as the changes that toasting intensity at cooperage produce in each polyphenolic profile. Before toasting, each wood shows a different and specific polyphenolic profile, with both qualitative and quantitative differences among them. Toasting notably changed these profiles, in general, proportionally to toasting intensity and led to a minor differentiation among species in toasted woods, although we also found phenolic markers in toasted woods. Thus, methyl syringate, benzoic acid, methyl vanillate, p-hydroxybenzoic acid, 3,4,5-trimethylphenol and p-coumaric acid, condensed tannins of the procyanidin type, and the flavonoids naringenin, aromadendrin, isosakuranetin and taxifolin will be a good tool to identify cherry wood. In acacia wood the chemical markers will be the aldehydes gallic and β-resorcylic and two not fully identified hydroxycinnamic compounds, condensed tannins of the prorobinetin type, and when using untoasted wood, dihydrorobinetin, and in toasted acacia wood, robinetin. In untoasted ash wood, the presence of secoiridoids, phenylethanoid glycosides, or di and oligolignols will be a good tool, especially oleuropein, ligstroside and olivil, together verbascoside and isoverbascoside in F. excelsior, and oleoside in F. americana. In toasted ash wood, tyrosol, syringaresinol, cyclolovil, verbascoside and olivil, could be used to identify the botanical origin. In addition, in ash wood, seasoned and toasted, neither hydrolysable nor condensed tannins were detected. Lastly, in chestnut wood, gallic and ellagic acids and hydrolysable tannins of both the gallotannin and ellagitannin type, can be used as chemical markers. Copyright © 2011 Elsevier B.V. All rights reserved.

Antioxidant activity and chemical components as potential anticancer agents in the olive leaf (Olea europaea L. cv Leccino.) decoction.

PubMed

De Marino, Simona; Festa, Carmen; Zollo, Franco; Nini, Antonella; Antenucci, Lina; Raimo, Gennaro; Iorizzi, Maria

2014-01-01

Epidemiological studies have shown that a reduced risk of chronic diseases such as cancer and cardiovascular diseases is correlated with a regular consumption of fruits and vegetable, many of which are rich in polyphenols. The additive and synergistic effect of phytochemicals in fruits and vegetables may reduce chronic diseases related to oxidative stress in human body. Olea europaea L. leaf are rich in phenolic components, which have been proposed to play a role in cancer prevention. The purpose of this study was to identify the main components in the Olea europaea L. leaf (cv. Leccino) preserved during the decoction preparation, in order to delineate the antioxidant activities of the crude extracts and its isolated compounds by using different in vitro assays including DPPH radicalscavenging capacity, total antioxidant capacity (TAC), xanthine oxidase (XO) inhibitory effect and the ability to delay the linoleic acid peroxidation process (ALP). The aqueous decoction was partitioned obtaining four extracts and the n-butanol extract showed the highest antioxidant activity and the highest total phenolic content. Phytochemical investigation leads to the isolation of thirteen secondary metabolites including simple phenolics, flavonoids, secoiridoids whose structures were elucidated by spectroscopic data (1D and 2D NMR) and spectrometric techniques. A significant free radical scavenging effect against DPPH has been evidenced in fraxamoside (1) (EC50 62.6 µM) and taxifolin (5) (EC50 50.0 µM), isolated for the first time from the water decoction. The most active compound in the TAC evaluation, was the 3,4 dihydro-phenyl glycol (8) (0.90 caffeic acid equiv.) while taxifolin and fraxamoside resulted as the most efficient inhibitors of XO activity (IC50 2.7 and 5.2 µM, respectively). Secoxyloganin (4), oleuropein (2) and tyrosol (6) showed the highest ALP activity. This study adds to the growing body of data supporting the bioactivities of phytochemicals and their potential impact on human health.

Inhibition of tyrosinase activity and melanine pigmentation by 2-hydroxytyrosol

PubMed Central

Uchida, Ryuji; Ishikawa, Seiko; Tomoda, Hiroshi

2014-01-01

2-Hydroxytyrosol (2-HT), originally reported as a synthetic compound, was isolated for the first time as a fungal metabolite. 2-HT was found to inhibit mushroom tyrosinase with an IC50 value of 13.0 µmol/L. Furthermore, 2-HT dose-dependently inhibited tyrosinase activity (IC50, 32.5 µmol/L) in the cell-free extract of B16 melanoma cells and α-melanocyte stimulating hormone (α-MSH)-stimulated melanin formation in intact B16 melanoma cells. PMID:26579376

Inhibition of tyrosinase activity and melanine pigmentation by 2-hydroxytyrosol.

PubMed

Uchida, Ryuji; Ishikawa, Seiko; Tomoda, Hiroshi

2014-04-01

2-Hydroxytyrosol (2-HT), originally reported as a synthetic compound, was isolated for the first time as a fungal metabolite. 2-HT was found to inhibit mushroom tyrosinase with an IC50 value of 13.0 µmol/L. Furthermore, 2-HT dose-dependently inhibited tyrosinase activity (IC50, 32.5 µmol/L) in the cell-free extract of B16 melanoma cells and α-melanocyte stimulating hormone (α-MSH)-stimulated melanin formation in intact B16 melanoma cells.

Phytochemical properties and anti-proliferative activity of Olea europaea L. leaf extracts against pancreatic cancer cells.

PubMed

Goldsmith, Chloe D; Vuong, Quan V; Sadeqzadeh, Elham; Stathopoulos, Costas E; Roach, Paul D; Scarlett, Christopher J

2015-07-17

Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial.

PubMed

Lockyer, Stacey; Rowland, Ian; Spencer, Jeremy Paul Edward; Yaqoob, Parveen; Stonehouse, Welma

2017-06-01

Dietary polyphenols have been demonstrated to favourably modify a number of cardiovascular risk markers such as blood pressure (BP), endothelial function and plasma lipids. We conducted a randomised, double-blind, controlled, crossover trial to investigate the effects of a phenolic-rich olive leaf extract (OLE) on BP and a number of associated vascular and metabolic measures. A total of 60 pre-hypertensive [systolic blood pressure (SBP): 121-140 mmHg; diastolic blood pressure (DBP): 81-90 mmHg] males [mean age 45 (±SD 12.7 years, BMI 26.7 (±3.21) kg/m 2 ] consumed either OLE (136 mg oleuropein; 6 mg hydroxytyrosol) or a polyphenol-free control daily for 6 weeks before switching to the alternate arm after a 4-week washout. Daytime [-3.95 (±SD 11.48) mmHg, p = 0.027] and 24-h SBP [-3.33 (±SD 10.81) mmHg, p = 0.045] and daytime and 24-h DBP [-3.00 (±SD 8.54) mmHg, p = 0.025; -2.42 (±SD 7.61) mmHg, p = 0.039] were all significantly lower following OLE intake, relative to the control. Reductions in plasma total cholesterol [-0.32 (±SD 0.70) mmol/L, p = 0.002], LDL cholesterol [-0.19 (±SD 0.56) mmol/L, p = 0.017] and triglycerides [-0.18 (±SD 0.48), p = 0.008] were also induced by OLE compared to control, whilst a reduction in interleukin-8 [-0.63 (±SD 1.13) pg/ml; p = 0.026] was also detected. Other markers of inflammation, vascular function and glucose metabolism were not affected. Our data support previous research, suggesting that OLE intake engenders hypotensive and lipid-lowering effects in vivo.

Olive (Olea europaea L.) Leaf Polyphenols Improve Insulin Sensitivity in Middle-Aged Overweight Men: A Randomized, Placebo-Controlled, Crossover Trial

PubMed Central

de Bock, Martin; Derraik, José G. B.; Brennan, Christine M.; Biggs, Janene B.; Morgan, Philip E.; Hodgkinson, Steven C.; Hofman, Paul L.; Cutfield, Wayne S.

2013-01-01

Background Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans. Objective To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men. Design Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4±5.5 years and BMI 28.0±2.0 kg/m2) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness. Results Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function. Conclusions Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome. Trial Registration Australian New Zealand Clinical Trials Registry #336317. PMID:23516412

Identification of p-hydroxybenzyl alcohol, tyrosol, phloretin and its derivate phloridzin as tyrosinase substrates.

PubMed

Ortiz-Ruiz, Carmen Vanessa; Berna, Jose; Garcia-Molina, Maria Del Mar; Tudela, Jose; Tomas, Virginia; Garcia-Canovas, Francisco

2015-07-01

In recent years, the hydroxyalkylphenols p-hydroxybenzyl alcohol and tyrosol, and the compound phloretin and its derivate phloridzin have been described as inhibitors of the enzyme tyrosinase. When the monophenolase and the diphenolase activities of tyrosinase on its physiological substrates l-dopa and/or l-tyrosine are measured in the presence of these compounds, the rate of action of the enzyme decreases. These findings led to the identification of these compounds as inhibitors. However, these molecules show an unusual behavior as inhibitors of the enzyme indeed, in this study, we demonstrate that they are not true inhibitors but alternative substrates of the enzyme. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylathion.

PubMed

De la Torre, Rafael; Corella, Dolores; Castañer, Olga; Martínez-González, Miguel A; Salas-Salvador, Jordi; Vila, Joan; Estruch, Ramón; Sorli, José V; Arós, Fernando; Fiol, Miquel; Ros, Emili; Serra-Majem, Lluís; Pintó, Xavier; Gómez-Gracia, Enrique; Lapetra, José; Ruiz-Canela, Miguel; Basora, José; Asensio, Eva Maria; Covas, Maria Isabel; Fitó, Montserrat

2017-06-01

Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against cardiovascular disease (CVD). Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3- O -methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality. Design: We included 1851 men and women with a mean ± SD age of 66.8 ± 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary hydroxytyrosol and HVAL and catechol- O -methyltransferase ( COMT ) rs4680 genotypes were measured. Results: After multivariable adjustment, all biomarkers were associated, as a continuous variable, with lower CVD risk, but only HVAL showed a strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison between quintiles. Only HVAL, as a continuous variable, was associated with total mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3, 12.1) additional years of life or years free of CVD, respectively, after 65 y. Individuals with the rs4680GG genotype had the highest HVAL concentrations ( P = 0.05). There was no association between COMT genotypes and events or interaction between COMT genotypes and HVAL concentrations. Conclusions: We report, for the first time to our knowledge, an independent association between high urinary HVAL concentrations and a lower risk of CVD and total mortality in elderly individuals. VOO and wine consumption and a high metabolic COMT capacity for methylation are key factors for high HVAL concentrations. The association that stems from our results reinforces the benefits of 2 key components of the Mediterranean diet (wine and VOO). This trial was registered at www.predimed.es as ISRCTN35739639. © 2017 American Society for Nutrition.

Melatonin and hydroxytyrosol protect against oxidative stress related to the central nervous system after the ingestion of three types of wine by healthy volunteers.

PubMed

Marhuenda, Javier; Medina, Sonia; Martínez-Hernández, Pedro; Arina, Simón; Zafrilla, Pilar; Mulero, Juana; Oger, Camille; Galano, Jean-Marie; Durand, Thierry; Ferreres, Federico; Gil-Izquierdo, Angel

2017-01-25

Adrenic acid (AdA) and docosahexaenoic acid (DHA) peroxidation produces F 2 -dihomo-IsoPs and neuroprostanes, which have been related to oxidative damage in the central nervous system. Besides polyphenols, melatonin (MEL) and hydroxytyrosol (OHTyr) could be partly responsible for the antioxidant benefits of red wine (excluding colon derivatives). In order to elucidate whether these compounds are responsible for the protective antioxidant effects of red wine, a double-blind, crossover, placebo-controlled in vivo study - involving the intake of red wines and their native musts by healthy volunteers - was performed. The urinary metabolites decreased after the administration of red wines, to a greater extent than after the intake of their corresponding musts or ethanol. Melatonin is the most effective compound that protects adrenic acid from oxidative attack, judged by the reduction in the formation of F 2 -dihomo-isoprostanes. Similarly, hydroxytyrosol, being the most effective bioactive compound in reducing the formation of F 3 -neuroprostanes n-6 DPA and F 4 -neuroprostanes, protected docosahexaenoic and eicosapentaenoic acids from oxidative attack.

Metabolic analysis of elicited cell suspension cultures of Cannabis sativa L. by (1)H-NMR spectroscopy.

PubMed

Pec, Jaroslav; Flores-Sanchez, Isvett Josefina; Choi, Young Hae; Verpoorte, Robert

2010-07-01

Cannabis sativa L. plants produce a diverse array of secondary metabolites. Cannabis cell cultures were treated with jasmonic acid (JA) and pectin as elicitors to evaluate their effect on metabolism from two cell lines using NMR spectroscopy and multivariate data analysis. According to principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA), the chloroform extract of the pectin-treated cultures were more different than control and JA-treated cultures; but in the methanol/water extract the metabolome of the JA-treated cells showed clear differences with control and pectin-treated cultures. Tyrosol, an antioxidant metabolite, was detected in cannabis cell cultures. The tyrosol content increased after eliciting with JA.

Differential Off-line LC-NMR (DOLC-NMR) Metabolomics To Monitor Tyrosine-Induced Metabolome Alterations in Saccharomyces cerevisiae.

PubMed

Hammerl, Richard; Frank, Oliver; Hofmann, Thomas

2017-04-19

A novel differential off-line LC-NMR approach (DOLC-NMR) was developed to capture and quantify nutrient-induced metabolome alterations in Saccharomyces cerevisiae. Off-line coupling of HPLC separation and 1 H NMR spectroscopy supported by automated comparative bucket analyses, followed by quantitative 1 H NMR using ERETIC 2 (electronic reference to access in vivo concentrations), has been successfully used to quantitatively record changes in the metabolome of S. cerevisiae upon intervention with the aromatic amino acid l-tyrosine. Among the 33 metabolites identified, glyceryl succinate, tyrosol acetate, tyrosol lactate, tyrosol succinate, and N-acyl-tyrosine derivatives such as N-(1-oxooctyl)-tyrosine are reported for the first time as yeast metabolites. Depending on the chain length, N-(1-oxooctyl)-, N-(1-oxodecanyl)-, N-(1-oxododecanyl)-, N-(1-oxomyristinyl)-, N-(1-oxopalmityl)-, and N-(1-oxooleoyl)-l-tyrosine imparted a kokumi taste enhancement above their recognition thresholds ranging between 145 and 1432 μmol/L (model broth). Finally, carbon module labeling (CAMOLA) and carbon bond labeling (CABOLA) experiments with 13 C 6 -glucose as the carbon source confirmed the biosynthetic pathway leading to the key metabolites; for example, the aliphatic side chain of N-(1-oxooctyl)-tyrosine could be shown to be generated via de novo fatty acid biosynthesis from four C 2 -carbon modules (acetyl-CoA) originating from glucose.

Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans.

PubMed

Mateos, Raquel; Martínez-López, Sara; Baeza Arévalo, Gema; Amigo-Benavent, Miryam; Sarriá, Beatriz; Bravo-Clemente, Laura

2016-08-15

Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non-enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA-glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanostructured starch combined with hydroxytyrosol in poly(vinyl alcohol) based ternary films as active packaging system.

PubMed

Luzi, Francesca; Fortunati, Elena; Di Michele, Alessandro; Pannucci, Elisa; Botticella, Ermelinda; Santi, Luca; Kenny, José Maria; Torre, Luigi; Bernini, Roberta

2018-08-01

Novel ternary films have been realized by using poly(vinyl alcohol) (PVA) as polymeric matrix, nanostructured starch as reinforcement phase and hydroxytyrosol (HTyr), a low-molecular phenolic compound present in olive oil, as antioxidant agent. Nanostructured starch, in the form of starch nanocrystals (NC) and nanoparticles (NP) obtained by acid hydrolysis and ultrasound irradiation of starch derived from the bread wheat variety Cadenza (WT, amylose content 33%) and a derived-high amylose line (HA, amylose content 75%), was considered. The developed multifunctional films were characterized in terms of morphological, thermal and optical properties, water absorption capacity, overall and specific migration into a food simulant and antioxidant properties. Experimental data showed a prolonged release of HTyr from all ternary films and the released HTyr retained a strong antioxidant activity. The data, compared to those of PVA/HTyr binary films, demonstrated the key role of nanostructured starch in the ternary formulations in promoting a gradual release of HTyr. Overall, PVA fillm combined with nanoparticles from low amylose starch and hydroxytyrosol resulted as the most promising ternary formulation for food packaging applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Skin delivery of antioxidant surfactants based on gallic acid and hydroxytyrosol.

PubMed

Alonso, Cristina; Lucas, Ricardo; Barba, Clara; Marti, Meritxell; Rubio, Laia; Comelles, Francesc; Morales, Juan Carlos; Coderch, Luisa; Parra, José Luís

2015-07-01

The aim of this study has been to investigate the dermal absorption profile of the antioxidant compounds gallic acid and hydroxytyrosol as well as their derivatives, hexanoate (hexyl gallate and hydroxytyrosol hexanoate) and octanoate (octyl gallate and octanoate derivative) alkyl esters (antioxidant surfactants). Previously, the scavenging capacity of these compounds, expressed as efficient dose ED50, has also determined. The percutaneous absorption of these compounds was obtained by an in vitro methodology using porcine skin biopsies on Franz static diffusion cells. The antiradical activity of compounds was determined using the 1,1-diphenyl-2-picrylhydrazyl free radical method. The percutaneous penetration results show the presence of antioxidants in all layers of the skin. The content of the cutaneously absorbed compound is higher for the antioxidant surfactants (ester derivatives). This particular behaviour could be due to the higher hydrophobicity of these compounds and the presence of surface activity in the antioxidant surfactants. These new antioxidant surfactants display optimum properties, which may be useful in the preparation of emulsified systems in cosmetic and pharmaceutical formulations because of their suitable surface activity and because they can protect the skin from oxidative damage. © 2015 Royal Pharmaceutical Society.

In vivo and in vitro addition of dried olive extract in poultry.

PubMed

King, Annie J; Griffin, Johanna K; Roslan, Fahkirah

2014-08-06

A freeze-dried powder from organic olive (Olea europaea) juice extract, contains 8.82% polyphenols and a minimum of 2.5% hydroxytyrosol (3,4-dihydroxyphenylethanol), an effective free radical scavenger and the major antioxidant in the byproduct (dried olive extract, DOE). Myricetin, a bioflavonoid extract from the bark powder of the bayberry tree (Myrica cerifera), also has many beneficial biological properties and antioxidative capacity. While well-known as antioxidants, the capacity of these compounds to retard lipid oxidation in foods containing unsaturated fatty acids has not been widely evaluated. Thus, a study was conducted to assess the capacity of DOE to (1) enhance the growth of poultry, (2) determine the effectiveness of DOE (administered in vivo) as an antioxidant in post-mortem tissue and further processed meat, and (3) compare the in vitro antioxidative capacity of hydroxytyrosol and myricetin. DOE was administered ad libitum in water at 6 and 12 mg per bird per day for 6 weeks in a factorial design: 3 diets (control plus two treatment levels) × 2 blocks × 2 replications. There was no enhancement of feed consumption, body weight (BW), or feed conversion by DOE; overall means for these measurements were 5.49 kg per bird, 3.32 kg per bird, and 1.65 g feed per g live BW, respectively. Diagnostic examinations of two birds per pen at the end of the study revealed no adverse effects due to consumption of DOE, a generally recognized as safe substance. The byproduct, administered in vivo, did not retard lipid oxidation in fresh, heated, or NaCl (1.0% w/w)/heated/stored meat as assessed by absorbance values for thiobarbituric acid reactive substances at 532 nm and 2,2-diphenylpicrylhydrazyl at 517 nm. Both the byproduct and hydroxytyrosol are highly water-soluble and may have been unavailable as an antioxidant in the tissue of broilers that did not consume water for 4-6 h prior to processing. As an additive in processed thigh meat, 6 and 12 mg of DOE (2.5% hydroxytyrosol) per 3 mg of meat, although not as effective as myricetin (95% purity), reduced oxidation. Further assessment revealed that hydroxytyrosol from the DOE, added at (1)/38 the concentration of myricetin, was almost 50% as effective.

Protection by extra virgin olive oil against oxidative stress in vitro and in vivo. Chemical and biological studies on the health benefits due to a major component of the Mediterranean diet.

PubMed

Rossi, Miriam; Caruso, Francesco; Kwok, Lorraine; Lee, Grace; Caruso, Alessio; Gionfra, Fabio; Candelotti, Elena; Belli, Stuart L; Molasky, Nora; Raley-Susman, Kathleen M; Leone, Stefano; Filipský, Tomáš; Tofani, Daniela; Pedersen, Jens; Incerpi, Sandra

2017-01-01

We report the results of in vivo studies in Caenorhabditis elegans nematodes in which addition of extra virgin olive oil (EVOO) to their diet significantly increased their life span with respect to the control group. Furthermore, when nematodes were exposed to the pesticide paraquat, they started to die after two days, but after the addition of EVOO to their diet, both survival percentage and lifespans of paraquat-exposed nematodes increased. Since paraquat is associated with superoxide radical production, a test for scavenging this radical was performed using cyclovoltammetry and the EVOO efficiently scavenged the superoxide. Thus, a linear correlation (y = -0.0838x +19.73, regression factor = 0.99348) was observed for superoxide presence (y) in the voltaic cell as a function of aliquot (x) additions of EVOO, 10 μL each. The originally generated supoeroxide was approximately halved after 10 aliquots (100 μL total). The superoxide scavenging ability was analyzed, theoretically, using Density Functional Theory for tyrosol and hydroxytyrosol, two components of EVOO and was also confirmed experimentally for the galvinoxyl radical, using Electron Paramagnetic Resonance (EPR) spectroscopy. The galvinoxyl signal disappeared after adding 1 μL of EVOO to the EPR cell in 10 minutes. In addition, EVOO significantly decreased the proliferation of human leukemic THP-1 cells, while it kept the proliferation at about normal levels in rat L6 myoblasts, a non-tumoral skeletal muscle cell line. The protection due to EVOO was also assessed in L6 cells and THP-1 exposed to the radical generator cumene hydroperoxide, in which cell viability was reduced. Also in this case the oxidative stress was ameliorated by EVOO, in line with results obtained with tetrazolium dye reduction assays, cell cycle analysis and reactive oxygen species measurements. We ascribe these beneficial effects to EVOO antioxidant properties and our results are in agreement with a clear health benefit of EVOO use in the Mediterranean diet.

Protection by extra virgin olive oil against oxidative stress in vitro and in vivo. Chemical and biological studies on the health benefits due to a major component of the Mediterranean diet

PubMed Central

Rossi, Miriam; Kwok, Lorraine; Lee, Grace; Caruso, Alessio; Gionfra, Fabio; Candelotti, Elena; Belli, Stuart L.; Molasky, Nora; Raley-Susman, Kathleen M.; Leone, Stefano; Filipský, Tomáš; Tofani, Daniela; Pedersen, Jens; Incerpi, Sandra

2017-01-01

We report the results of in vivo studies in Caenorhabditis elegans nematodes in which addition of extra virgin olive oil (EVOO) to their diet significantly increased their life span with respect to the control group. Furthermore, when nematodes were exposed to the pesticide paraquat, they started to die after two days, but after the addition of EVOO to their diet, both survival percentage and lifespans of paraquat-exposed nematodes increased. Since paraquat is associated with superoxide radical production, a test for scavenging this radical was performed using cyclovoltammetry and the EVOO efficiently scavenged the superoxide. Thus, a linear correlation (y = -0.0838x +19.73, regression factor = 0.99348) was observed for superoxide presence (y) in the voltaic cell as a function of aliquot (x) additions of EVOO, 10 μL each. The originally generated supoeroxide was approximately halved after 10 aliquots (100 μL total). The superoxide scavenging ability was analyzed, theoretically, using Density Functional Theory for tyrosol and hydroxytyrosol, two components of EVOO and was also confirmed experimentally for the galvinoxyl radical, using Electron Paramagnetic Resonance (EPR) spectroscopy. The galvinoxyl signal disappeared after adding 1 μL of EVOO to the EPR cell in 10 minutes. In addition, EVOO significantly decreased the proliferation of human leukemic THP-1 cells, while it kept the proliferation at about normal levels in rat L6 myoblasts, a non-tumoral skeletal muscle cell line. The protection due to EVOO was also assessed in L6 cells and THP-1 exposed to the radical generator cumene hydroperoxide, in which cell viability was reduced. Also in this case the oxidative stress was ameliorated by EVOO, in line with results obtained with tetrazolium dye reduction assays, cell cycle analysis and reactive oxygen species measurements. We ascribe these beneficial effects to EVOO antioxidant properties and our results are in agreement with a clear health benefit of EVOO use in the Mediterranean diet. PMID:29283995

In vitro and in vivo safety evaluation of Acer tegmentosum.

PubMed

Hwang, Youn-Hwan; Park, Hwayong; Ma, Jin Yeul

2013-06-21

Acer tegmentosum, which contains salidroside and tyrosol, has been used for the treatment of hepatic disorders in eastern Asia. However, little is known about its safety. To determine the safety of Acer tegmentosum, we evaluated its acute oral toxicity and genotoxicity profiles. Salidroside and tyrosol present in Acer tegmentosum were quantified using high-performance liquid chromatography. Acute oral toxicity testing of Acer tegmentosum was performed in rats. Genotoxicity of Acer tegmentosum was assessed by bacterial reverse mutation, chromosomal aberration, and bone marrow micronucleus tests. All the tests were conducted in accordance with the good laboratory practices. The amounts of salidroside and tyrosol in Acer tegmentosum were found to be 85.01±1.21mg/g and 3.12±0.04mg/g, respectively. In the bacterial reverse mutation test, Acer tegmentosum increased the number of revertant Salmonella typhimurium TA98 colonies, regardless of metabolic activation by S9 mixture. In contrast, Acer tegmentosum application did not significantly increase the number of chromosomal aberrations in Chinese hamster ovary (CHO)-K1 cells and micronucleated polychromatic erythrocytes in mice. In the acute oral toxicity test, the median lethal dose (LD50) of Acer tegmentosum was found to be >2000mg/kg in rats. Take together, Acer tegmentosum exhibits mutagenicity, which was evident from the bacterial reverse mutation test. Further studies are needed to identify the components responsible for such an effect and the underlying mechanisms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Physicochemical properties of natural phenolics from grapes and olive oil byproducts and their antioxidant activity in frozen horse mackerel fillets.

PubMed

Pazos, Manuel; Alonso, Ana; Fernández-Bolaños, Juan; Torres, Josep L; Medina, Isabel

2006-01-25

The reducing and chelating capacities and the affinity for the incorporation into the fish muscle of grape procyanidins, hydroxytyrosol, and propyl gallate were studied together with their antioxidant activity in frozen horse mackerel (Trauchurus trauchurus) fillets. Fillets were supplemented with phenolic antioxidants by (a) spraying an aqueous phenolic solution, (b) glazing with an aqueous phenolic solution, and (c) a previous washing of fillets with water plus spraying an aqueous phenolic solution. The effect of washing on the endogenous pro-oxidant/antioxidant balance of the fillets was also determined. All phenolic compounds were effective delaying lipid oxidation in the fish fillets. The order of antioxidant efficiency in spraying and glazing was propyl gallate > hydroxytyrosol > procyanidins, which was similar to the reducing power of these phenolics, but did not show any correlation with their chelating capacity and their affinity to the fish muscle. Washing the fillets with water prior to spraying phenols increased synergistically the antioxidant activity of grape procyanidins and changed the relative antioxidant efficiency to propyl gallate approximately procyanidins > hydroxytyrosol. This synergism may be a result of a better distribution of the procyanidins onto the fillet surface because of the residual water that remained on the fillets surface after washing.

Peracetylated hydroxytyrosol, a new hydroxytyrosol derivate, attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome, Nrf2/HO1 and JAK/STAT signaling pathways.

PubMed

Montoya, Tatiana; Aparicio-Soto, Marina; Castejón, María Luisa; Rosillo, María Ángeles; Sánchez-Hidalgo, Marina; Begines, Paloma; Fernández-Bolaños, José G; Alarcón-de-la-Lastra, Catalina

2018-03-18

The present study was designed to investigate the anti-inflammatory effects of a new derivative of hydroxytyrosol (HTy), peracetylated hydroxytyrosol (Per-HTy), compared with its parent, HTy, on lipopolysaccharide (LPS)-stimulated murine macrophages as well as potential signaling pathways involved. In particular, we attempted to characterize the role of the inflammasome underlying Per-HTy possible anti-inflammatory effects. Isolated murine peritoneal macrophages were treated with HTy or its derivative in the presence or absence of LPS (5 μg/ml) for 18 h. Cell viability was determined using sulforhodamine B (SRB) assay. Nitric oxide (NO) production was analyzed by Griess method. Production of pro-inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA) and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (STAT3), haem oxigenase 1 (HO1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and mitogen-activated protein kinases (MAPKs) activation was determined by Western blot. Per-HTy significantly reduced the levels of NO and pro-inflammatory cytokines as well as both COX-2 and iNOS expressions. Furthermore, Per-HTy treatment inhibited STAT3 and increased Nrf2 and HO1 protein levels in murine macrophages exposed to LPS. In addition, Per-HTy anti-inflammatory activity was related with an inhibition of non-canonical nucleotide binding domain (NOD)-like receptor (NLRP3) inflammasome pathways by decreasing pro-inflammatory interleukin (IL)-1β and IL-18 cytokine levels as consequence of regulation of cleaved caspase-11 enzyme. These results support that this new HTy derivative may offer a new promising nutraceutical therapeutic strategy in the management of inflammatory-related pathologies. Copyright © 2018. Published by Elsevier Inc.

Characterization of antioxidant phenolics in Syringa vulgaris L. flowers and fruits by HPLC-DAD-ESI-MS.

PubMed

Tóth, Gergő; Barabás, Csenge; Tóth, Anita; Kéry, Ágnes; Béni, Szabolcs; Boldizsár, Imre; Varga, Erzsébet; Noszál, Béla

2016-06-01

In this study the polyphenolic composition of lilac flowers and fruits was determined for the first time. For the identification of compounds, accurate molecular masses and formulas, acquired by LC and ESI-TOF-MS and fragmentation pattern given by LC-ESI/MS/MS analyses, were used. Our chromatographic system in conjunction with tandem MS was found to be valuable in the rapid separation and determination of the multiple constituents in methanolic extracts of lilac flowers and fruits. Altogether 34 phenolics, comprising 18 secoiridoids, seven phenylpropanoids, four flavonoids and five low-molecular-weight phenols, were identified. As marker compounds two secoiridoids (oleuropein and nuzhenide), two phenylpropanoids (acteoside and echinacoside) and rutin were quantified by validated methods. As a result of quantitative analysis, it was confirmed that flowers contain significant amounts of phenylpropanoids (acteoside, 2.48%; echinacoside, 0.75%) and oleuropein (0.95%), while in fruits secoiridoid oleuropein (1.09%) and nuzhenide (0.42%) are the major secondary metabolites. The radical scavenging activities of the extracts and the constituents were investigated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)] assays. Both extracts show remarkable antioxidant activities. Our results clearly show that lilac flowers and fruits are inexpensive, readily available natural sources of phenolic compounds with pharmacological and cosmetic applications. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Bioaccessibility of hydroxytyrosol and n-3 fatty acids as affected by the delivery system: simple, double and gelled double emulsions.

PubMed

Cofrades, Susana; Bou, Ricard; Flaiz, Linda; Garcimartín, Alba; Benedí, Juana; Mateos, Raquel; Sánchez-Muniz, Francisco J; Olivero-David, Raúl; Jiménez-Colmenero, Francisco

2017-06-01

This study examines the influence of different food-grade n-3 PUFA-enriched simple emulsion (SE), double emulsion (DE) and gelled double emulsion (GDE) delivery systems on the extent of lipolysis, antioxidant capacity and the bioaccessibility of hydroxytyrosol (HTy). GDE emulsion offered better protection for HTy (89%) than the other systems (79% in SE and DE). The reducing capacity of the emulsions containing HTy were not altered during oral digestion. However, "in vitro" gastric and intestinal phases significantly reduced the antioxidant activity of all systems. The structural and physical state of GDE entailed a slowing-down of triacylglyceride hydrolysis (36.4%) in comparison with that of SE and DE (22.7 and 24.8% for SE and DE, respectively).

Hydroxytyrosol extracts, olive oil and walnuts as functional components in chicken sausages.

PubMed

Nieto, Gema; Martínez, Lorena; Castillo, Julian; Ros, Gaspar

2017-08-01

Olive oil, hydroxytyrosol and walnut can be considered ideal Mediterranean ingredients for their high polyphenolic content and healthy properties. Three extracts of hydroxytyrosol obtained using different extraction processes (HXT 1, 2, 3) (50 ppm) were evaluated for use as antioxidants in eight different chicken sausage formulas enriched in polyunsaturated fatty acids (2.5 g 100 g -1 walnut) or using extra virgin olive oil (20 g 100 g -1 ) as fat replacer. Lipid and protein oxidation, colour, emulsion stability, and the microstructure of the resulting chicken sausages were investigated and a sensory analysis was carried out. The sausages with HXT extracts were found to decrease lipid oxidation and to lead to the loss of thiol groups compared with control sausages. Emulsion stability (capacity to hold water and fat) was greater in the sausages containing olive oil and walnut than in control sausages. In contrast, the HXT extracts produced high emulsion instability (increasing cooking losses). Sensory analysis suggested that two of the HXT extracts studied (HXT 2 and HXT 3 ) were unacceptable, while the acceptability of the other was similar to that of the control products. Sausages incorporating HXT showed different structures than control samples or sausages with olive oil, related to the composition of the emulsion. These results suggest the possibility of replacing animal fat by olive oil and walnut in order to produce healthy meat products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Selection of Lactobacillus plantarum strains to use as starters in fermented table olives: Oleuropeinase activity and phage sensitivity.

PubMed

Zago, Miriam; Lanza, Barbara; Rossetti, Lia; Muzzalupo, Innocenzo; Carminati, Domenico; Giraffa, Giorgio

2013-05-01

Fermented table olives (Olea europaea L.) are largely diffused in the Mediterranean area. Olives are picked at different stages of maturity and after harvesting, processed to eliminate the characteristic bitterness caused by the presence of the oleuropein glucoside and to become suitable for human consumption. The spontaneous fermentation of table olives mainly depends on lactic acid bacteria (LAB), and in particular on Lactobacillus plantarum which plays an important role in the degradation of oleuropein. The hydrolysis of oleuropein is attributed to the β-glucosidase and esterase activities of the indigenous LAB microflora. This study investigated the potential of L. plantarum strains isolated from dairy products and olives to be used as starters for fermented table olives. Forty-nine strains were typed by RAPD-PCR and investigated for the presence of the β-glucosidase (bglH) gene. The full sequence of the bglH gene was carried out. All the 49 L. plantarum strains were also tested for phage resistance. A total of six strains were selected on the basis of genotypic polymorphism, bglH gene sequence analysis, and phage resistance profile. These strains were further characterized to assess the acidifying capability, the growth at different temperatures, the tolerance to different NaCl concentrations, and the oleuropeinolytic activity. Although further characterizations are required, especially concerning the influence on sensory properties, L. plantarum proved to have the potential to be used as a debittering and fermentative agent in starter culture for fermented table olives. Copyright © 2012 Elsevier Ltd. All rights reserved.

Manganese soil and foliar fertilization of olive plantlets: the effect on leaf mineral and phenolic content and root mycorrhizal colonization.

PubMed

Pasković, Igor; Ćustić, Mirjana Herak; Pecina, Marija; Bronić, Josip; Ban, Dean; Radić, Tomislav; Pošćić, Filip; Jukić Špika, Maja; Soldo, Barbara; Palčić, Igor; Goreta Ban, Smiljana

2018-06-08

The aim of this study was to examine the effect of foliar (Mn_fol) and soil Zeolite-Mn (Mn_ZA) application on leaf mineral, total phenolic and oleuropein content, and mycorrhizae colonization of self-rooted cv. Leccino plantlets grown on calcareous soil. The dissolution of zeolite was 97% when citric acid was applied at 0.05 mM dm -3 , suggesting that organic acids excreted by roots can dissolve modified zeolite (Mn_ZA) making Mn available for plant uptake. The leaf Mn concentration was the highest for Mn_fol treatment at 90 DAT (172 mg kg -1 ) and 150 DAT (70 mg kg -1 ) compared to other treatments. Mn_ZA soil application increased leaf Mn concentration at 150 DAT compared to control and NPK treatment. The oleuropein leaf content was highest for Mn_fol compared to other treatments at 90 DAT and lowest at 150 DAT. Arbuscular mycorrhizal colonization was higher for Mn_fol treatment at 150 DAT compared to all other treatments. Changes in the arbuscular colonization percentage and oleuropein content may be connected to stress conditions provoked by high leaf Mn concentration in Mn_fol treatment at 90 DAT. Mn_ZA application increased leaf Mn concentration at 150 DAT compared to control and NPK treatments. It can be assumed that the dominant mechanism in Mn uptake from modified zeolite is Mn_ZA dissolution through root exudates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effect of hydroxytyrosol on quality of sulfur dioxide-free red wine.

PubMed

Raposo, R; Ruiz-Moreno, M J; Garde-Cerdán, T; Puertas, B; Moreno-Rojas, J M; Gonzalo-Diago, A; Guerrero, R F; Ortiz, V; Cantos-Villar, E

2016-02-01

In this work, the feasibility of two commercial products enriched in hydroxytyrosol (HT) as alternative to sulfur dioxide in Syrah red wines was evaluated. The HT enriched products came from synthesis and from olive waste. Wines treated with HT were compared with wines treated with sulfur dioxide at two winemaking stages: bottling and after 6 months of storage in bottle. Minor differences were found in enological parameters and volatile composition (esters, alcohols and acids). Significant differences were observed in color related parameters and sensory analysis. HT wines improved color parameters as well as scents and tasting at bottling. However, after 6 months of storage in bottle HT wines were more oxidized than SO2 wines. The olfactometry profile of HT wines supported sensory analysis. HT wines showed new odorant zones from both the added product and oxidation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protective effect of hydroxytyrosol in arsenic-induced mitochondrial dysfunction in rat brain.

PubMed

Soni, Manisha; Prakash, Chandra; Sehwag, Sfurti; Kumar, Vijay

2017-07-01

The present study was planned to investigate the protective effect of hydroxytyrosol (HT) against arsenic (As)-induced mitochondrial dysfunction in rat brain. Rats exposed to sodium arsenite (25 ppm for 8 weeks) showed decreased mitochondrial complexes (I, II, IV) activities, mitochondrial superoxide dismutase (MnSOD), and catalase activities in brain mitochondria. As-treated rats showed reduced mRNA expression of complex I (ND-1, ND-2), IV (COX-1, COX-4) subunits, and uncoupling protein-2 (UCP-2). In addition to this, As exposure downregulated the protein expression of MnSOD. Administration of HT with As restored the enzymatic activities of mitochondrial complexes, MnSOD and catalase, increased the mRNA levels of complexes subunits and UCP-2 as well as proteins level of MnSOD. These results suggest that HT efficiently restores mitochondrial dysfunction in As neurotoxicity and might be used as potential mitoprotective agent in future. © 2017 Wiley Periodicals, Inc.

Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

PubMed

Kotronoulas, Aristotelis; Pizarro, Nieves; Serra, Aida; Robledo, Patricia; Joglar, Jesús; Rubió, Laura; Hernaéz, Alvaro; Tormos, Carmen; Motilva, Ma José; Fitó, Montserrat; Covas, Maria-Isabel; Solà, Rosa; Farré, Magí; Saez, Guillermo; de la Torre, Rafael

2013-11-01

Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested. Copyright © 2013. Published by Elsevier Ltd.

Nutritional implications of olives and sugar: attenuation of post-prandial glucose spikes in healthy volunteers by inhibition of sucrose hydrolysis and glucose transport by oleuropein.

PubMed

Kerimi, Asimina; Nyambe-Silavwe, Hilda; Pyner, Alison; Oladele, Ebun; Gauer, Julia S; Stevens, Yala; Williamson, Gary

2018-03-09

The secoiridoid oleuropein, as found in olives and olive leaves, modulates some biomarkers of diabetes risk in vivo. A possible mechanism may be to attenuate sugar digestion and absorption. We explored the potential of oleuropein, prepared from olive leaves in a water soluble form (OLE), to inhibit digestive enzymes (α-amylase, maltase, sucrase), and lower [ 14 C(U)]-glucose uptake in Xenopus oocytes expressing human GLUT2 and [ 14 C(U)]-glucose transport across differentiated Caco-2 cell monolayers. We conducted 7 separate crossover, controlled, randomised intervention studies on healthy volunteers (double-blinded and placebo-controlled for the OLE supplement) to assess the effect of OLE on post-prandial blood glucose after consumption of bread, glucose or sucrose. OLE inhibited intestinal maltase, human sucrase, glucose transport across Caco-2 monolayers, and uptake of glucose by GLUT2 in Xenopus oocytes, but was a weak inhibitor of human α-amylase. OLE, in capsules, in solution or as naturally present in olives, did not affect post-prandial glucose derived from bread, while OLE in solution attenuated post-prandial blood glucose after consumption of 25 g sucrose, but had no effect when consumed with 50 g of sucrose or glucose. The combined inhibition of sucrase activity and of glucose transport observed in vitro was sufficient to modify digestion of low doses of sucrose in healthy volunteers. In comparison, the weak inhibition of α-amylase by OLE was not enough to modify blood sugar when consumed with a starch-rich food, suggesting that a threshold potency is required for inhibition of digestive enzymes in order to translate into in vivo effects.

Therapeutic properties in Tunisian hot springs: first evidence of phenolic compounds in the cyanobacterium Leptolyngbya sp. biomass, capsular polysaccharides and releasing polysaccharides.

PubMed

Trabelsi, Lamia; Mnari, Amira; Abdel-Daim, Mohamed M; Abid-Essafi, Salwa; Aleya, Lotfi

2016-12-13

In Tunisia, the use of hot spring waters for both health and recreation is a tradition dating back to Roman times. In fact, thermal baths, usually called "Hammam" are recommended as a therapeutic and prophylactic measure against many types of illness and toxicity. While the chemical concentration of thermal water is admittedly associated with its therapeutic effects, the inclusion in spa waters of efficient bioproduct additives produced by photosynthetic microorganisms and that act against oxidative stress may comprise a significant supplementary value for thermal centers. The aim of this study was to investigate the antioxidant potential of the Tunisian thermophilic cyanobacterium Leptolyngbya sp. and to determine its phytochemical constituents and phenolic profile. BME (Biomass Methanolic Extract), CME (Capsular polysaccharides Methanolic Extract) and RME (Releasing polysaccharides Methanolic Extract) of Leptolyngbya sp. were examined for their antioxidant activities by means of DPPH, hydroxyl radical scavenging and ferrous ion chelating assays. Their total phenols, flavonoids, carotenoids, Mycosporine-like amino acids (MAAs) and vitamin C contents, as well as their phenolic profiles were also determined. BME has the highest content of phenols (139 ± 1.2 mg/g), flavonoids (34.9 ± 0.32 mg CEQ/g), carotenoids (2.03 ± 0.56 mg/g) and vitamin C (15.7 ± 1.55 mg/g), while the highest MAAs content (0.42 ± 0.03 mg/g) was observed in CME. BME presented both the highest DPPH and hydroxyl radical scavenging ability with an IC 50 of 0.07 and 0.38 mg/ml, respectively. The highest ferrous chelating capacity was detected in CME with an IC 50  = 0.59 mg/ml. Phenolic profiles revealed the presence of 25 phenolic compounds with the existence of hydroxytyrosol, oleuropein, resveratrol and pinoresinol. The study demonstrated that the cyanobacterium Leptolyngbya sp. possesses abundant natural antioxidant products which may have prophylactic and therapeutic effects on many types of illness and toxicity. The present findings not only explain and reinforce the rationale behind traditional therapeutic practices in Tunisia in the exploitation of the country's hot springs, but support the addition of Leptolyngbya to thermal waters as a means to enhance the value and reputation of the curative nature of Tunisian thermal waters.

Antiviral efficacy against hepatitis B virus replication of oleuropein isolated from Jasminum officinale L. var. grandiflorum.

PubMed

Zhao, Guiqin; Yin, Zhifeng; Dong, Junxing

2009-09-07

Jasminum officinale L. var. grandiflorum (JOG) is a folk medicine used for the treatment of hepatitis in south of China. Phytochemical studies showed that secoiridoid glycosides are the typical constituents of this plant. The present study was undertaken to evaluate the effect of oleuropein (Ole) derived from the flowers of JOG on hepatitis B virus (HBV) replication in HepG2 2.2.15 cell line in vitro and duck hepatitis B virus (DHBV) replication in ducklings in vivo. The extracellular hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) concentrations in cell culture medium were determined by ELISA. DHBV in duck serum was analyzed by dot blot. Ole blocks effectively HBsAg secretion in HepG2 2.2.15 cells in a dose-dependent manner (IC(50)=23.2 microg/ml). Ole (80 mg/kg, intraperitoneally, twice daily) also reduced viremia in DHBV-infected ducks. Ole therefore warrants further investigation as a potential therapeutic agent for HBV infection.

Contribution of flavonoids to the overall radical scavenging activity of olive (Olea europaea L.) leaf polar extracts.

PubMed

Goulas, Vlassios; Papoti, Vassiliki T; Exarchou, Vassiliki; Tsimidou, Maria Z; Gerothanassis, Ioannis P

2010-03-24

The contribution of flavonoids to the overall radical scavenging activity of olive leaf polar extracts, known to be good sources of oleuropein related compounds, was examined. Off line and on line HPLC-DPPH(*) assays were employed, whereas flavonoid content was estimated colorimetrically. Individual flavonoid composition was first assessed by RP-HPLC coupled with diode array and fluorescence detectors and verified by LC-MS detection system. Olive leaf was found a robust source of flavonoids regardless sampling parameters (olive cultivar, leaf age or sampling date). Total flavonoids accounted for the 13-27% of the total radical scavenging activity assessed using the on line protocol. Luteolin 7-O-glucoside was one of the dominant scavengers (8-25%). Taking into consideration frequency of appearance the contribution of luteolin (3-13%) was considered important, too. Our findings support that olive leaf, except for oleuropein and related compounds, is also a stable source of bioactive flavonoids.

Hydroxyframoside B, a secoiridoid of Fraxinus rhynchophylla, inhibits adipocyte differentiation in 3T3-L1 cells.

PubMed

Choi, Kyeong-Mi; Shin, Eunjin; Liu, Qing; Yoo, Hwan-Soo; Kim, Young Choong; Sung, Sang Hyun; Hwang, Bang Yeon; Lee, Mi Kyeong

2011-07-01

Fraxinus rhynchophylla showed significant inhibitory activity on adipocyte differentiation in the 3T3-L1 preadipocyte cell line as assessed by measuring fat accumulation using Oil Red O staining. Further fractionation led to the isolation of two secoiridoids, oleuropein and hydroxyframoside B. Hydroxyframoside B significantly reduced fat accumulation and triglyceride content in differentiated 3T3-L1 cells without affecting cell viability, whereas oleuropein showed little effect. Further studies with interval treatment demonstrated that hydroxyframoside B exerted inhibitory activity on adipocyte differentiation when treated within 2 days (days 0-2) after differentiation induction. In addition, hydroxyframoside B significantly blocked the induction of adipogenic transcription factors such as C/EBP α, C/EBP β, and PPAR γ. Taken together, these results suggest that hydroxyframoside B inhibited early/middle stage of adipogenic differentiation, in part, via inhibition of C/EBP α, C/EBP β, and PPAR γ-dependent pathways. © Georg Thieme Verlag KG Stuttgart · New York.

Melatonin and hydroxytyrosol-rich wines influence the generation of DNA oxidation catabolites linked to mutagenesis after the ingestion of three types of wine by healthy volunteers.

PubMed

Marhuenda, Javier; Medina, Sonia; Martínez-Hernández, Pedro; Arina, Simón; Zafrilla, Pilar; Mulero, Juana; Genieser, Hans-Gottfried; Ferreres, Federico; Gil-Izquierdo, Ángel

2016-12-07

The Mediterranean Diet (MD) has been proved to exert benefits with respect to the maintenance of the redox balance, and wine is a representative component. Bioactive compounds such as polyphenols, melatonin and hydroxytyrosol act as radical scavengers and regulate the oxidation status of organisms. Oxidative damage to DNA yields a large range of end products. The repair of oxidized DNA entails the removal of the useless bases and/or nucleotides as well as the release of circulating nucleotides and nucleosides. The current research aims to elucidate, for the first time, the DNA protection against oxidative stress provided by three types of red wine - relating it to the intake of bioactive compounds - after the intake of a serving of red wine/must by 18 healthy female volunteers during a short term double-blind, crossover and placebo-controlled study. The novelty of our work is to describe the importance of melatonin and hydroxytyrosol and its metabolites (from gut microflora) in comparison with polyphenols in a red wine matrix (excluding colon derivatives). The results show that the intake of red wine and must secondarily reduces oxidative stress and carcinogenesis due to their content of homovanillic acid, as measured by decreases in the plasmatic concentration of 8-hydroxy-2'deoxyguanosine, 8-hydroxyguanine, and 8-nitroguanosine. Moreover, the intake of wine appears to exert vasodilatory effects, mediated by the action of nitric oxide and increased plasma guanosine-3'-5'-cyclic monophosphate plasmatic levels, owing to the intake of wines higher in melatonin and homovanillic acid. Therefore, the results obtained in the present study revealed that polyphenols, despite being the major compounds in the red wine matrix, are not the most effective compounds protecting DNA from oxidative attack.

Human absorption of a supplement containing purified hydroxytyrosol, a natural antioxidant from olive oil, and evidence for its transient association with low-density lipoproteins.

PubMed

González-Santiago, Maria; Fonollá, Juristo; Lopez-Huertas, Eduardo

2010-04-01

There is growing interest in the health effects of olive oil polyphenols, particularly hydroxytyrosol (HT), for their potential application in the treatment of inflammatory conditions such as cardiovascular disease (CVD). As oxidative modification of low-density lipoproteins (LDL) plays a central role in the development of CVD, natural antioxidants are a main target for the nutraceutical industry. In this study we firstly investigated the absorption of pure hydroxytyrosol (99.5%) administered as a supplement in an aqueous solution (2.5mg/kg BW) in the plasma and urine of healthy volunteers (n=10). Plasma C(max) for HT and homovanillic alcohol (HvOH) were detected at 13.0+/-1.5 and 16.7+/-2.4min, respectively. The HT and HvOH levels were undetectable 2-h after the administration. HT, HvOH, homovanillic acid and 3,4-dihydroxyphenylacetic acid were found as free forms (44%) or as glucuronide (34.4%) or sulphate (21.2%) conjugates in the 24-h urine samples of the subjects. In a second phase of the study, the same amounts of HT were administered to the subjects and the presence of HT in purified plasma lipoproteins was investigated in LDL fractions freshly isolated. 10min after the ingestion of the HT supplement, more than 50% of the total amount detected was present in the LDL-purified fractions and its concentration declined in accordance with its presence in plasma but no changes were found in total antioxidant capacity, malondialdehyde or LDL lag time. These results indicate that pure HT transiently associates with LDL lipoproteins in vivo. Copyright 2009 Elsevier Ltd. All rights reserved.

Synthesis and antioxidant evaluation of isochroman-derivatives of hydroxytyrosol: structure-activity relationship.

PubMed

Mateos, Raquel; Madrona, Andrés; Pereira-Caro, Gema; Domínguez, Vanessa; Cert, Rosa M A; Parrado, Juan; Sarriá, Beatriz; Bravo, Laura; Espartero, José Luis

2015-04-15

Isochroman-derivatives of the natural olive oil phenol hydroxytyrosol (HT) have been synthesised via Oxa-Pictet-Spengler reaction in high yields. Lipophilicity and antioxidant activity were determined to establish the structure-activity relationship of isochromans compared to HT, BHT and α-tocopherol. Antioxidant capacity was tested in two different media: bulk oils, using the Rancimat test, and brain homogenates, by measuring malondialdehyde (MDA) levels as a lipoperoxidation biomarker. In addition, other antioxidant assays (FRAP, ABTS and ORAC) were carried out. Rancimat and MDA results show that antioxidant activity was related with lipophilicity, directly in brain homogenates and inversely in the oils, in agreement with the polar paradox. Free o-diphenolic groups positively determined the activity in the oils, whereas reducing and radical-scavenging activities were related to the number of free hydroxyl moieties. BHT and α-tocopherol showed lower antioxidant activity than isochromans and HT. We conclude that HT-isochromans present significant potential as bioactive compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders.

PubMed

Peyrol, Julien; Riva, Catherine; Amiot, Marie Josèphe

2017-03-20

Virgin olive oil (VOO) constitutes the main source of fat in the Mediterranean diet. VOO is rich in oleic acid, displaying health-promoting properties, but also contains minor bioactive components, especially phenolic compounds. Hydroxytyrosol (HT), the main polyphenol of olive oil, has been reported to be the most bioactive component. This review aims to compile the results of clinical, animal and cell culture studies evaluating the effects of HT on the features of Metabolic Syndrome (MetS) (body weight/adiposity, dyslipidemia, hypertension, and hyperglycemia/insulin resistance) and associated complications (oxidative stress and inflammation). HT was able to improve the lipid profile, glycaemia, and insulin sensitivity, and counteract oxidative and inflammatory processes. Experimental studies identified multiple molecular targets for HT conferring its beneficial effect on health in spite of its low bioavailability. However, rodent experiments and clinical trials with pure HT at biologically relevant concentrations are still lacking. Moreover, the roles of intestine and its gut microbiota have not been elucidated.

Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders

PubMed Central

Peyrol, Julien; Riva, Catherine; Amiot, Marie Josèphe

2017-01-01

Virgin olive oil (VOO) constitutes the main source of fat in the Mediterranean diet. VOO is rich in oleic acid, displaying health-promoting properties, but also contains minor bioactive components, especially phenolic compounds. Hydroxytyrosol (HT), the main polyphenol of olive oil, has been reported to be the most bioactive component. This review aims to compile the results of clinical, animal and cell culture studies evaluating the effects of HT on the features of Metabolic Syndrome (MetS) (body weight/adiposity, dyslipidemia, hypertension, and hyperglycemia/insulin resistance) and associated complications (oxidative stress and inflammation). HT was able to improve the lipid profile, glycaemia, and insulin sensitivity, and counteract oxidative and inflammatory processes. Experimental studies identified multiple molecular targets for HT conferring its beneficial effect on health in spite of its low bioavailability. However, rodent experiments and clinical trials with pure HT at biologically relevant concentrations are still lacking. Moreover, the roles of intestine and its gut microbiota have not been elucidated. PMID:28335507

The LC-MS-based metabolomics of hydroxytyrosol administration in rats reveals amelioration of the metabolic syndrome.

PubMed

Lemonakis, Nikolaos; Poudyal, Hemant; Halabalaki, Maria; Brown, Lindsay; Tsarbopoulos, Anthony; Skaltsounis, Alexios-Leandros; Gikas, Evagelos

2017-01-15

Hydroxytyrosol (HT), an important component of olive fruit and olive oil, improves the signs of metabolic syndrome in rats following chronic treatment. At a dose of 20mg/kg/day, HT decreased adiposity and improved cardiovascular and liver structure and function in rats fed with a high-carbohydrate, high-fat diet. An untargeted metabolomics approach has been employed using both UPLC-Orbitrap and -QqTOF methods to identify the changes induced by chronic HT administration on the plasma metabolome. 31 metabolites have been found to be differentially expressed between the examined groups. HT was shown to decrease biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, and the metabolism of linoleic acid, retinol, sphingolipids and arachidonic acid, whereas glycerolipid metabolism is up-regulated. These are plausible mechanisms for the attenuation by HT of cardiovascular, liver and metabolic changes in high-carbohydrate, high-fat diet fed rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective effect of hydroxytyrosol and its metabolite homovanillic alcohol on H(2)O(2) induced lipid peroxidation in renal tubular epithelial cells.

PubMed

Deiana, Monica; Incani, Alessandra; Rosa, Antonella; Corona, Giulia; Atzeri, Angela; Loru, Debora; Paola Melis, M; Assunta Dessì, M

2008-09-01

We investigated the capacity of hydroxytyrosol (HT), 3,4-dihydroxyphenylethanol, and homovanillic alcohol (HVA), 4-hydroxy-3-methoxy-phenylethanol, to inhibit H(2)O(2) induced oxidative damage in LLC-PK1, a porcine kidney epithelial cell line, studying the effect of H(2)O(2) on specific cell membrane lipid targets, unsaturated fatty acids and cholesterol. Exposure to H(2)O(2) induced a significant increase of the level of MDA together with a disruption of the membrane structure, with the loss of unsaturated fatty acids, cholesterol and alpha-tocopherol, and the formation of fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with HT protected renal cells from oxidative damage: the level of membrane lipids was preserved and there was no significant detection of oxidation products. HVA exerted a comparable activity, thus both HT and HVA were able to prevent in renal cells the lipid peroxidation process that plays a central role in tubular cell injury.

Innovative method for recovery and valorization of hydroxytyrosol from olive mill wastewaters.

PubMed

Bonetti, A; Venturini, S; Ena, A; Faraloni, C

2016-01-01

The nutritional properties of olive oil can be attributed to its oleic acid and phenolic compounds content, acting as natural oxidants to prevent human diseases. In particular, hydroxytyrosol has an anti-inflammatory action similar to omega 3 fatty acids from fish oil. The olive oil production was conducted by two extraction procedures: first, a two-phase extraction giving extra-virgin olive oil and humid pomace, second, a three-phase working process of humid pomace, obtaining another minimum quantity of extra-virgin olive oil, 'dry' pomace devoid of polyphenols, and mill wastewaters rich in anti-oxidant compounds. The aim of this processing was to employ water to extract the highest concentration of polyphenols from humid pomace and convey them in oil mill wastewaters for extraction. Processed olives were 37,200 kg, pomace deprived of polyphenols was equal to 20,400 kg and processing was performed with 500 kg of olives per hour. This method offers advantages of using cheap equipment and technical simplicity.

Tyrosol and its metabolites as antioxidative and anti-inflammatory molecules in human endothelial cells.

PubMed

Muriana, Francisco J G; Montserrat-de la Paz, Sergio; Lucas, Ricardo; Bermudez, Beatriz; Jaramillo, Sara; Morales, Juan C; Abia, Rocio; Lopez, Sergio

2017-08-01

Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion, Tyr undergoes extensive first pass intestinal/hepatic metabolism. However, knowledge about the biological effects of Tyr metabolites is scarce. We chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL) metabolites and explored their properties against oxidative stress and inflammation in TNF-α-treated human umbilical vein endothelial cells (hECs). Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of glutathione, and the down-regulation of glutathione peroxidase 1, glutamate-cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-κB signaling proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr-GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose-dependent manner, ameliorated plantar and ear edemas in mice models of acute and chronic inflammation. This study demonstrates the antioxidant and/or anti-inflammatory properties of Tyr metabolites, with Tyr-SUL being the most effective.

Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity.

PubMed

Vauzour, David; Corona, Giulia; Spencer, Jeremy P E

2010-09-01

Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-)-epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids. Copyright © 2010. Published by Elsevier Inc.

Benefit of Oleuropein Aglycone for Alzheimer's Disease by Promoting Autophagy.

PubMed

Cordero, Joaquín G; García-Escudero, Ramón; Avila, Jesús; Gargini, Ricardo; García-Escudero, Vega

2018-01-01

Alzheimer's disease is a proteinopathy characterized by accumulation of hyperphosphorylated Tau and β -amyloid. Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. Autophagy deficiency has been demonstrated in Alzheimer's patients impairing effective elimination of aggregates and damaged mitochondria, leading to their accumulation, increasing their toxicity and oxidative stress. In the present study, we demonstrated by microarray analysis the downregulation of fundamental autophagy and mitophagy pathways in Alzheimer's patients. The benefits of the Mediterranean diet on Alzheimer's disease and cognitive impairment are well known, attributing this effect to several polyphenols, such as oleuropein aglycone (OLE), present in extra virgin olive oil. OLE is able to induce autophagy, achieving a decrease of aggregated proteins and a reduction of cognitive impairment in vivo. This effect is caused by the modulation of several pathways including the AMPK/mTOR axis and the activation of autophagy gene expression mediated by sirtuins and histone acetylation or EB transcription factor. We propose that supplementation of diet with extra virgin olive oil might have potential benefits for Alzheimer's patients by the induction of autophagy by OLE.

Combination of Analytical and Chemometric Methods as a Useful Tool for the Characterization of Extra Virgin Argan Oil and Other Edible Virgin Oils. Role of Polyphenols and Tocopherols.

PubMed

Rueda, Ascensión; Samaniego-Sánchez, Cristina; Olalla, Manuel; Giménez, Rafael; Cabrera-Vique, Carmen; Seiquer, Isabel; Lara, Luis

2016-01-01

Analysis of phenolic profile and tocopherol fractions in conjunction with chemometrics techniques were used for the accurate characterization of extra virgin argan oil and eight other edible vegetable virgin oils (olive, soybean, wheat germ, walnut, almond, sesame, avocado, and linseed) and to establish similarities among them. Phenolic profile and tocopherols were determined by HPLC coupled with diode-array and fluorescence detectors, respectively. Multivariate factor analysis (MFA) and linear correlations were applied. Significant negative correlations were found between tocopherols and some of the polyphenols identified, but more intensely (P < 0.001) between the γ-tocopherol and oleuropein, pinoresinol, and luteolin. MFA revealed that tocopherols, especially γ-fraction, most strongly influenced the oil characterization. Among the phenolic compounds, syringic acid, dihydroxybenzoic acid, oleuropein, pinoresinol, and luteolin also contributed to the discrimination of the oils. According to the variables analyzed in the present study, argan oil presented the greatest similarity with walnut oil, followed by sesame and linseed oils. Olive, avocado, and almond oils showed close similarities.

Benefit of Oleuropein Aglycone for Alzheimer's Disease by Promoting Autophagy

PubMed Central

Cordero, Joaquín G.; García-Escudero, Ramón

2018-01-01

Alzheimer's disease is a proteinopathy characterized by accumulation of hyperphosphorylated Tau and β-amyloid. Autophagy is a physiological process by which aggregated proteins and damaged organelles are eliminated through lysosomal digestion. Autophagy deficiency has been demonstrated in Alzheimer's patients impairing effective elimination of aggregates and damaged mitochondria, leading to their accumulation, increasing their toxicity and oxidative stress. In the present study, we demonstrated by microarray analysis the downregulation of fundamental autophagy and mitophagy pathways in Alzheimer's patients. The benefits of the Mediterranean diet on Alzheimer's disease and cognitive impairment are well known, attributing this effect to several polyphenols, such as oleuropein aglycone (OLE), present in extra virgin olive oil. OLE is able to induce autophagy, achieving a decrease of aggregated proteins and a reduction of cognitive impairment in vivo. This effect is caused by the modulation of several pathways including the AMPK/mTOR axis and the activation of autophagy gene expression mediated by sirtuins and histone acetylation or EB transcription factor. We propose that supplementation of diet with extra virgin olive oil might have potential benefits for Alzheimer's patients by the induction of autophagy by OLE. PMID:29675133

The olive compound 4-hydroxytyrosol inactivates Staphyloccoccus aureus bacteria and Staphylococcal enterotoxin A (SEA)

USDA-ARS?s Scientific Manuscript database

The foodborne pathogen Staphylococcus aureus produces the virulent staphylococcal enterotoxin A (SEA), a single chain protein which consists of 233 amino acid residues with a molecular weight of 27,078 Da. SEA is a superantigen that is reported to contribute to animal (mastitis) and human (emesis, ...

Thermal Decomposition Behavior of Hydroxytyrosol (HT) in Nitrogen Atmosphere Based on TG-FTIR Methods.

PubMed

Tu, Jun-Ling; Yuan, Jiao-Jiao

2018-02-13

The thermal decomposition behavior of olive hydroxytyrosol (HT) was first studied using thermogravimetry (TG). Cracked chemical bond and evolved gas analysis during the thermal decomposition process of HT were also investigated using thermogravimetry coupled with infrared spectroscopy (TG-FTIR). Thermogravimetry-Differential thermogravimetry (TG-DTG) curves revealed that the thermal decomposition of HT began at 262.8 °C and ended at 409.7 °C with a main mass loss. It was demonstrated that a high heating rate (over 20 K·min -1 ) restrained the thermal decomposition of HT, resulting in an obvious thermal hysteresis. Furthermore, a thermal decomposition kinetics investigation of HT indicated that the non-isothermal decomposition mechanism was one-dimensional diffusion (D1), integral form g ( x ) = x ², and differential form f ( x ) = 1/(2 x ). The four combined approaches were employed to calculate the activation energy ( E = 128.50 kJ·mol -1 ) and Arrhenius preexponential factor (ln A = 24.39 min -1 ). In addition, a tentative mechanism of HT thermal decomposition was further developed. The results provide a theoretical reference for the potential thermal stability of HT.

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetic Retinopathy: Relationship with Cardiovascular Biomarkers.

PubMed

González-Correa, José Antonio; Rodríguez-Pérez, María Dolores; Márquez-Estrada, Lucía; López-Villodres, Juan Antonio; Reyes, José Julio; Rodriguez-Gutierrez, Guillermo; Fernández-Bolaños, Juan; De La Cruz, José Pedro

2018-01-24

The aim of the study was to test the neuroprotective effect of hydroxytyrosol (HT) on experimental diabetic retinopathy. Animals were divided in four groups: (1) control nondiabetic rats, (2) streptozotocin-diabetic rats (DR), (3) DR treated with 1 mg/kg/day p.o. HT, and (4) DR treated with 5 mg/kg/day p.o. HT. Treatment with HT was started 7 days before inducing diabetes and was maintained for 2 months. In the DR group, total area occupied by extracellular matrix was increased, area occupied by retinal cells was decreased; both returned to near-control values in DR rats treated with HT. The number of retinal ganglion cells in DR was significantly lower (44%) than in the control group, and this decrease was smaller after HT treatment (34% and 9.1%). Linear regression analysis showed that prostacyclin, platelet aggregation, peroxynitrites, and the dose of 5 mg/kg/day HT significantly influenced retinal ganglion cell count. In conclusion, HT exerted a neuroprotective effect on diabetic retinopathy, and this effect correlated significantly with changes in some cardiovascular biomarkers.

Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetes Mellitus.

PubMed

Reyes, José Julio; Villanueva, Beatriz; López-Villodres, Juan Antonio; De La Cruz, José Pedro; Romero, Lidia; Rodríguez-Pérez, María Dolores; Rodriguez-Gutierrez, Guillermo; Fernández-Bolaños, Juan; González-Correa, José Antonio

2017-06-07

The aim of the study was to analyze the possible neuroprotective effect of hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats (10 animals/group) were distributed in five groups: nondiabetic rats, control diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in brain slices was tested. The DR group showed increased cell death, oxidative and nitrosative stress, and an increase in brain inflammatory mediators. These alterations were significantly greater in DR than in normoglycemic animals. HT significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and brain inflammatory mediators (18.6-40.6% prostaglandin E 2 and 17.0-65.0% interleukin 1β concentration). Cell death was reduced by 25.9, 37.5, and 41.0% after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in rats with experimental diabetes thus had a neuroprotective effect.

Lipophilization of Hydroxytyrosol-Enriched Fractions from Olea europaea L. Byproducts and Evaluation of the in Vitro Effects on a Model of Colorectal Cancer Cells.

PubMed

Bernini, Roberta; Carastro, Isabella; Palmini, Gaia; Tanini, Annalisa; Zonefrati, Roberto; Pinelli, Patrizia; Brandi, Maria Luisa; Romani, Annalisa

2017-08-09

A hydroxytyrosol (HTyr)-enriched fraction containing HTyr 6% w/w, derived from Olea europaea L. byproducts and obtained using an environmentally and economically sustainable technology, was lipophilized under green chemistry conditions. The effects of three fractions containing hydroxytyrosyl butanoate, octanoate, and oleate, named, respectively, lipophilic fractions 5, 6, and 7, and unreacted HTyr on the human colon cancer cell line HCT8-β8 engineered to overexpress estrogen receptor β (ERβ) were evaluated and compared to those of pure HTyr. The experimental data demonstrated that HTyr and all fractions showed an antiproliferative effect, as had been observed by the evaluation of the cellular doubling time under these different conditions (mean control, 32 ± 4 h; HTyr 1, 65 ± 9 h; fraction 5, 64 ± 11 h; fraction 6, 62 ± 14 h; fraction 7, 133 ± 30 h). As evidenced, fraction 7 containing hydroxytyrosyl oleate showed the highest activity. These results were related to the link with ER-β, which was assessed through simultaneous treatment with an inhibitor of ERβ.

Phytotoxic Metabolites Produced by Diaporthella cryptica, the Causal Agent of Hazelnut Branch Canker.

PubMed

Cimmino, Alessio; Nocera, Paola; Linaldeddu, Benedetto Teodoro; Masi, Marco; Gorecki, Marcin; Pescitelli, Gennaro; Montecchio, Lucio; Maddau, Lucia; Evidente, Antonio

2018-04-04

From the culture filtrates of Diaporthella cryptica, an emerging hazelnut pathogen, 2-hydroxy-3-phenylpropanoate methyl ester and its 3-(4-hydroxyphenyl) and 3-(1 H-indol-3-yl) analogues, named crypticins A-C, were isolated together with the well-known tyrosol. Crypticins A-C were identified by spectroscopic (essentially nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry) methods. The R absolute configuration (AC) of crypticin A was determined by comparing its optical rotation and electronic circular dichroism (ECD) spectrum with those of papuline, the methyl ester of (-)( S)-phenyllactic acid isolated as the main phytotoxin of Pseudomonas syringae pv.  papulans, responsible for apple blister spot. The ACs of crypticins B and C were determined by time-dependent density functional theory calculations of their ECD spectra. Papuline and the new metabolites herein isolated, except tyrosol, were tested at 1 mg/mL on cork oak, grapevine, hazelnut, and holm oak leaves using the leaf puncture assay. They were also tested on tomato cuttings at 0.5 and 0.05 mg/mL. In the leaf puncture assay, none of the compounds was found to be active. Crypticin C and papuline were active in the tomato cutting assay. Additionally, crypticin C displayed moderate inhibitory effect against Phytophthora cambivora.

Chemical and Biological Investigation of Olive Mill Waste Water - OMWW Secoiridoid Lactones.

PubMed

Vougogiannopoulou, Konstantina; Angelopoulou, Maria T; Pratsinis, Harris; Grougnet, Raphaël; Halabalaki, Maria; Kletsas, Dimitris; Deguin, Brigitte; Skaltsounis, Leandros A

2015-08-01

Olive mill waste water is the major byproduct of the olive oil industry containing a range of compounds related to Olea europaea and olive oil constituents. Olive mill waste water comprises an important environmental problem in olive oil producing countries, but it is also a valuable material for the isolation of high added value compounds. In this study, an attempt to investigate the secoiridoid content of olive mill waste water is described with the aid of ultrahigh-performance liquid chromatography-electrospray ionization (±)-high-resolution mass spectrometry and centrifugal partition chromatography methods. In total, seven secoiridoid lactones were isolated, four of which are new natural products. This is the first time that a conjugate of hydroxytyrosol and a secoiridoid lactone has been isolated from olive mill waste water and structurally characterized. Furthermore, the range of isolated compounds allowed for the proposal of a hypothesis for the biotransformation of olive secoiridoids during the production of olive mill waste water. Finally, the ability of the representative compounds to reduce the intracellular reactive oxygen species was assessed with the dichlorofluorescein assay in conjunction with the known antioxidant agent hydroxytyrosol. Georg Thieme Verlag KG Stuttgart · New York.

Metabolite analysis of endophytic fungi from cultivars of Zingiber officinale Rosc. identifies myriad of bioactive compounds including tyrosol.

PubMed

Anisha, C; Radhakrishnan, E K

2017-06-01

Endophytic fungi associated with rhizomes of four cultivars of Zingiber officinale were identified by molecular and morphological methods and evaluated for their activity against soft rot pathogen Pythium myriotylum and clinical pathogens. The volatile bioactive metabolites produced by these isolates were identified by GC-MS analysis of the fungal crude extracts. Understanding of the metabolites produced by endophytes is also important in the context of raw consumption of ginger as medicine and spice. A total of fifteen isolates were identified from the four varieties studied. The various genera identified were Acremonium sp., Gliocladiopsis sp., Fusarium sp., Colletotrichum sp., Aspergillus sp., Phlebia sp., Earliella sp., and Pseudolagarobasidium sp. The endophytic community was unique to each variety, which could be due to the varying host genotype. Fungi from phylum Basidiomycota were identified for the first time from ginger. Seven isolates showed activity against Pythium, while only two showed antibacterial activity. The bioactive metabolites identified in the fungal crude extracts include tyrosol, benzene acetic acid, ergone, dehydromevalonic lactone, N-aminopyrrolidine, and many bioactive fatty acids and their derivatives which included linoleic acid, oleic acid, myristic acid, n-hexadecanoic acid, palmitic acid methyl ester, and methyl linoleate. The presence of these varying bioactive endophytic fungi may be one of the reasons for the differences in the performance of the different ginger varieties.

Hydroxytyrosol and its complex forms (secoiridoids) modulate aorta and heart proteome in healthy rats: Potential cardio-protective effects.

PubMed

Catalán, Úrsula; Rubió, Laura; López de Las Hazas, Maria-Carmen; Herrero, Pol; Nadal, Pedro; Canela, Núria; Pedret, Anna; Motilva, Maria-José; Solà, Rosa

2016-10-01

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-LC and MS. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed higher fold change values compared to HT, attributed to higher concentration of HT detected in heart tissue. Changes at proteomic level in cardiovascular tissues may partially account for the underlying mechanisms of VOO phenols cardiovascular protection being the SEC effects higher than free HT. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice.

PubMed

Chashmi, Nooshin Ahmadian; Emadi, Sarvenaz; Khastar, Hossein

2017-01-22

Gentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice. Male mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected. Gentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen. Findings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT. Copyright © 2016 Elsevier Inc. All rights reserved.

Oleuropein Prevents Azoxymethane-Induced Colon Crypt Dysplasia and Leukocytes DNA Damage in A/J Mice.

PubMed

Sepporta, Maria Vittoria; Fuccelli, Raffaela; Rosignoli, Patrizia; Ricci, Giovanni; Servili, Maurizio; Fabiani, Roberto

2016-08-19

Previous studies have shown that the precursor of olive oil secoiridoids, Oleuropein (OL) has several in vitro chemopreventive properties. OL inhibits proliferation and induces apoptosis in breast, thyroid, prostate, and colorectal cancer (CRC) cells. Much less is known about the effects of OL on animal models of carcinogenesis. In this study, we investigated the ability of OL to prevent the azoxymethane (AOM)-induced colon cancer upset and DNA damage in mice. Animals, fed with a basal diet either enriched or not with OL (125 mg/kg), were injected with AOM (10 mg/kg, once a week for 6 weeks) and sacrificed after either 7 weeks for histological analysis of colon crypt dysplasia and evaluation of DNA damage in leukocytes or 17 weeks for counting the macroscopically observable colon tumors. An OL-enriched diet prevented the AOM-induced preneoplastic lesions in different colon segments, reducing the severity of crypt dysplasia and DNA damage in peripheral leukocytes. In addition, OL significantly reduced the AOM-induced tumor incidence from 57% to 14% (P < .05, chi-square test) in the medial colon segment. This study shows that OL is able to prevent CRC and DNA damage in mice treated with the carcinogen AOM. These results stimulate further human cancer prevention studies with OL-enriched food supplements that are actually available on the market.

Oleuropein, a natural extract from plants, offers neuroprotection in focal cerebral ischemia/reperfusion injury in mice.

PubMed

Yu, Hailong; Liu, Peipei; Tang, Hui; Jing, Jian; Lv, Xiang; Chen, Lanlan; Jiang, Li; Xu, Jun; Li, Jun

2016-03-15

Oleuropein (OLE) was found to have anti-inflammatory and anti-oxidant effects. The latest study has shown that it can resist myocardial injury that follows an acute myocardial infarction and can rescue impaired spinal nerve cells. In this study, we investigated the neuroprotective effects of OLE on cerebral ischemia and reperfusion injury in a middle cerebral artery occlusion model in mice.OLE (100 mg/kg) was injected intraperitoneally 1h before ischemia. We found that the volume of cerebral infarction was significantly reduced after 75 min of ischemia and 24 h of reperfusion compared with the I/R (ischemia/reperfusion) group. This protective function occurred in a dose-dependent manner. We also found that treatment with OLE could reduce the cerebral infarct volume. The neuroprotective effect was prolonged from 2 h to 4 h when we injected OLE intracerebroventricularly after reperfusion. We then found that OLE can decrease the level of cleavedcaspase-3, an important marker of apoptosis, in the ischemic mouse brain. Finally, we explored the role of OLE in providing anti-apoptotic effects through the increased expression of Bcl-2 and the decreased expression of Bax, which are important markers in apoptosis. As shown above, the function and safety of OLE in cardiovascular disease may indicate that it is a potential therapeutic for stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

An Oleuropein β-Glucosidase from Olive Fruit Is Involved in Determining the Phenolic Composition of Virgin Olive Oil

PubMed Central

Velázquez-Palmero, David; Romero-Segura, Carmen; García-Rodríguez, Rosa; Hernández, María L.; Vaistij, Fabián E.; Graham, Ian A.; Pérez, Ana G.; Martínez-Rivas, José M.

2017-01-01

Phenolic composition of virgin olive oil is determined by the enzymatic and/or chemical reactions that take place during olive fruit processing. Of these enzymes, β-glucosidase activity plays a relevant role in the transformation of the phenolic glycosides present in the olive fruit, generating different secoiridoid derivatives. The main goal of the present study was to characterize olive fruit β-glucosidase genes and enzymes responsible for the phenolic composition of virgin olive oil. To achieve that, we have isolated an olive β-glucosidase gene from cultivar Picual (OepGLU), expressed in Nicotiana benthamiana leaves and purified its corresponding recombinant enzyme. Western blot analysis showed that recombinant OepGLU protein is detected by an antibody raised against the purified native olive mesocarp β-glucosidase enzyme, and exhibits a deduced molecular mass of 65.0 kDa. The recombinant OepGLU enzyme showed activity on the major olive phenolic glycosides, with the highest levels with respect to oleuropein, followed by ligstroside and demethyloleuropein. In addition, expression analysis showed that olive GLU transcript level in olive fruit is spatially and temporally regulated in a cultivar-dependent manner. Furthermore, temperature, light and water regime regulate olive GLU gene expression in olive fruit mesocarp. All these data are consistent with the involvement of OepGLU enzyme in the formation of the major phenolic compounds present in virgin olive oil. PMID:29163620

Oleuropein isolated from Fraxinus rhynchophylla inhibits glutamate-induced neuronal cell death by attenuating mitochondrial dysfunction.

PubMed

Kim, Mi Hye; Min, Ju-Sik; Lee, Joon Yeop; Chae, Unbin; Yang, Eun-Ju; Song, Kyung-Sik; Lee, Hyun-Shik; Lee, Hong Jun; Lee, Sang-Rae; Lee, Dong-Seok

2017-04-27

Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases.

Fate and Prediction of Phenolic Secoiridoid Compounds throughout the Different Stages of the Virgin Olive Oil Making Process

PubMed Central

2017-01-01

The evolution of the main phenolic secoiridoid compounds throughout the different stages of the virgin olive oil making process—crushing, malaxation and liquid-solid separation—is studied here, with the goal of making possible the prediction of the partition and transformation that take place in the different steps of the process. The concentration of hydroxytyrosol secoiridoids produced under the different crushing conditions studied are reasonably proportional to the intensity of the milling stage, and strongly depend on the olive variety processed. During malaxation, the content of the main phenolic secoiridoids is reduced, especially in the case of the hydroxytyrosol derivatives, in which a variety-dependent behaviour is observed. The prediction of the concentration of phenolic secoiridoids finally transferred from the kneaded paste to the virgin olive oil is also feasible, and depends on the phenolic content and amount of water in the olive paste. The determination of the phenolic compounds in the olive fruit, olive paste and olive oil has been carried out by LC-MS (Liquid-Chromatography Mass-Spectrometry). This improved knowledge could help in the use of more adequate processing conditions for the production of virgin olive oil with desired properties; for example, higher or lower phenolic content, as the amount of these minor components is directly related to its sensory, antioxidant and healthy properties. PMID:28771173

Optimization of Ripe Olive Processing with a Single Lye Treatment.

PubMed

Brenes, Manuel; Romero, Concepción; García-García, Pedro

2017-09-01

The development of a method for darkening black ripe olives during the washing step with a single NaOH treatment and preservation liquid was studied. Olives of the Hojiblanca cultivar were darkened at pilot plant scale, packed, sterilized, and analyzed after 2 mo of storage at ambient temperature. It was found that the use of a mixture of preservation liquid:water at a ratio of 1:1 during the first washing gave rise to darker olives with slightly better firmness and no effect on sensory quality. However, care must be taken with the concentration of acetic acid in the preservation solution, as a content of this organic acid higher than 25 g/L can cause adverse effects on olive color due to the low pH that can be reached in the flesh of the fruit. Additionally, the re-use of the preservation solution in the first washing resulted in enrichment in antioxidant compounds of the packed product. Black ripe olives processed with preservation liquid had a total phenolic content of 629 mg/kg, whereas those with only tap water had 376 mg/kg, in particular hydroxytyrosol and hydroxytyrosol-4-glucoside. These findings mean that it is possible to get darker olives with higher contents in bioactive substances by reusing the preservation liquid during the darkening step of black ripe olives. © 2017 Institute of Food Technologists®.

Fate and Prediction of Phenolic Secoiridoid Compounds throughout the Different Stages of the Virgin Olive Oil Making Process.

PubMed

Fregapane, Giuseppe; Salvador, M Desamparados

2017-08-03

The evolution of the main phenolic secoiridoid compounds throughout the different stages of the virgin olive oil making process-crushing, malaxation and liquid-solid separation-is studied here, with the goal of making possible the prediction of the partition and transformation that take place in the different steps of the process. The concentration of hydroxytyrosol secoiridoids produced under the different crushing conditions studied are reasonably proportional to the intensity of the milling stage, and strongly depend on the olive variety processed. During malaxation, the content of the main phenolic secoiridoids is reduced, especially in the case of the hydroxytyrosol derivatives, in which a variety-dependent behaviour is observed. The prediction of the concentration of phenolic secoiridoids finally transferred from the kneaded paste to the virgin olive oil is also feasible, and depends on the phenolic content and amount of water in the olive paste. The determination of the phenolic compounds in the olive fruit, olive paste and olive oil has been carried out by LC-MS (Liquid-Chromatography Mass-Spectrometry). This improved knowledge could help in the use of more adequate processing conditions for the production of virgin olive oil with desired properties; for example, higher or lower phenolic content, as the amount of these minor components is directly related to its sensory, antioxidant and healthy properties.

Prostaglandin E2 from Candida albicans Stimulates the Growth of Staphylococcus aureus in Mixed Biofilms

PubMed Central

Krause, Jan; Geginat, Gernot; Tammer, Ina

2015-01-01

Background Previous studies showed that Staphylococcus aureus and Candida albicans interact synergistically in dual species biofilms resulting in enhanced mortality in animal models. Methodology/Principal Findings The aim of the current study was to test possible candidate molecules which might mediate this synergistic interaction in an in vitro model of mixed biofilms, such as farnesol, tyrosol and prostaglandin (PG) E2. In mono-microbial and dual biofilms of C.albicans wild type strains PGE2 levels between 25 and 250 pg/mL were measured. Similar concentrations of purified PGE2 significantly enhanced S.aureus biofilm formation in a mode comparable to that observed in dual species biofilms. Supernatants of the null mutant deficient in PGE2 production did not stimulate the proliferation of S.aureus and the addition of the cyclooxygenase inhibitor indomethacin blocked the S.aureus biofilm formation in a dose-dependent manner. Additionally, S. aureus biofilm formation was boosted by low and inhibited by high farnesol concentrations. Supernatants of the farnesol-deficient C. albicans ATCC10231 strain significantly enhanced the biofilm formation of S. aureus but at a lower level than the farnesol producer SC5314. However, C. albicans ATCC10231 also produced PGE2 but amounts were significantly lower compared to SC5314. Conclusion/Significance In conclision, we identified C. albicans PGE2 as a key molecule stimulating the growth and biofilm formation of S. aureus in dual S. aureus/C. albicans biofilms, although C. albicans derived farnesol, but not tyrosol, may also contribute to this effect but to a lesser extent. PMID:26262843

Identification of Predominant Phytochemical Compounds and Cytotoxic Activity of Wild Olive Leaves (Olea europaea L. ssp. sylvestris) Harvested in South Portugal.

PubMed

Makowska-Wąs, Justyna; Galanty, Agnieszka; Gdula-Argasińska, Joanna; Tyszka-Czochara, Małgorzata; Szewczyk, Agnieszka; Nunes, Ricardo; Carvalho, Isabel S; Michalik, Marta; Paśko, Paweł

2017-03-01

This study has been aimed at providing a qualitative and quantitative evaluation of selected phytochemicals such as phenolic acids, flavonoids, oleuropein, fatty acids profile, and volatile oil compounds, present in wild olive leaves harvested in Portugal, as well as at determining their antioxidant and cytotoxic potential against human melanoma HTB-140 and WM793, prostate cancer DU-145 and PC-3, hepatocellular carcinoma Hep G2 cell lines, as well as normal human skin fibroblasts BJ and prostate epithelial cells PNT2. Gallic, protocatechuic, p-hydroxybenzoic, vanillic acids, apigenin 7-O-glucoside, luteolin 7-O-glucoside, and rutin were identified in olive leaves. The amount of oleuropein was equal to 22.64 g/kg dry weight. (E)-Anethole (32.35%), fenchone (11.89%), and (Z)-3-nonen-1-ol (8%) were found to be the main constituents of the oil volatile fraction, whereas palmitic, oleic, and alpha-linolenic acid were determined to be dominating fatty acids. Olive leaves methanol extract was observed to exerted a significant, selective cytotoxic effect on DU-145 and PC-3 cell lines. Except the essential oil composition, evaluated wild olive leaves, with regard to their quantitative and qualitative composition, do not substantially differ from the leaves of other cultivars grown for industrial purposes and they reveal considerable antioxidant and cytotoxic properties. Thus, the wild species may prove to be suitable for use in traditional medicine as cancer chemoprevention. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Quantification of bioactive compounds in Picual and Arbequina olive leaves and fruit.

PubMed

Romero, Concepción; Medina, Eduardo; Mateo, Mª Antonia; Brenes, Manuel

2017-04-01

Olive leaves and fruit possess bioactive substances such as phenolic compounds and triterpenic acids that can be obtained from olive by-products generated during olive oil extraction. The aim of the present study was the characterization and quantification of these compounds in Picual and Arbequina cultivars from different locations and throughout two seasons in both olive leaves and fruit. The major phenolic compound identified in the leaves was oleuropein, and the total content of phenolic compounds in this material reached 70 g kg -1 fresh weight. The leaves were also rich in triterpenic acids (20 g kg -1 fresh weight), with oleanolic acid being the most concentrated among them. With regard to olives, oleuropein and demethyloleuropein were the main phenolic compounds in the pulp of Picual and Arbequina cultivars, and the total concentration of these phenolic compounds reached 3.5% fresh weight. Olives can also be an important source of triterpenic acids, although this is mainly the skin part, where the maslinic and oleanolic acids are concentrated. Olive leaves can contain up to 70 g kg -1 phenolic compounds and 20 g kg -1 triterpenic acids, and olive fruit can contain up to 35 g kg -1 of the former and 3 g kg -1 of the latter. It must also be noted that this level was constant both between seasons and orchard locations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Multiple Biological Effects of Olive Oil By-products such as Leaves, Stems, Flowers, Olive Milled Waste, Fruit Pulp, and Seeds of the Olive Plant on Skin.

PubMed

Kishikawa, Asuka; Ashour, Ahmed; Zhu, Qinchang; Yasuda, Midori; Ishikawa, Hiroya; Shimizu, Kuniyoshi

2015-06-01

As olive oil production increases, so does the amount of olive oil by-products, which can cause environmental problems. Thus, new ways to utilize the by-products are needed. In the present study, five bioactive characteristics of olive oil by-products were assessed, namely their antioxidant, anti-bacterial, anti-melanogenesis, anti-allergic, and collagen-production-promoting activities. First, the extracts of leaves (May and October), stems (May and October), flowers, olive milled waste, fruit pulp and seeds were prepared using two safe solvents, ethanol and water. According to HPLC and LC/MS analysis and Folin-Ciocalteu assay, the ethanol extracts of the leaves (May and October), stems (May and October) and flowers contained oleuropein, and the ethanol extract of the stems showed the highest total phenol content. Oleuropein may contribute to the antioxidant and anti-melanogenesis activities of the leaves, stems, and flowers. However, other active compounds or synergistic effects present in the ethanol extracts are also likely to contribute to the anti-bacterial activity of the leaves and flowers, the anti-melanogenesis activity of some parts, the anti-allergic activity of olive milled waste, and the collagen-production-promoting activity of the leaves, stems, olive milled waste and fruit pulp. This study provides evidence that the by-products of olive oil have the potential to be further developed and used in the skin care industry. Copyright © 2015 John Wiley & Sons, Ltd.

Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles.

PubMed

Siddique, Muhammad Irfan; Katas, Haliza; Amin, Mohd Cairul Iqbal Mohd; Ng, Shiow-Fern; Zulfakar, Mohd Hanif; Buang, Fhataheya; Jamil, Adawiyah

2015-12-01

Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effect of resveratrol, tyrosol and beta-sitosterol on oxidised low-density lipoprotein-stimulated oxidative stress, arachidonic acid release and prostaglandin E2 synthesis by RAW 264.7 macrophages.

PubMed

Vivancos, Marta; Moreno, Juan J

2008-06-01

Oxidation of LDL is hypothesised as an early and critical event in atherogenesis. Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses others and alters cell lipid metabolism. Consumption of a Mediterranean diet is associated with a low incidence of atherosclerotic disease, but data about the specific dietary constituents involved and mechanisms conferring cardioprotection are still sparse. The aim of the present study was to determine the effect of representative minor components of wine and olive oil on reactive oxygen species and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed that exposure to non-toxic oxLDL concentrations leads to the production of H2O2 by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo-oxygenase-2 overexpression and subsequent PGE2 release. We observed that resveratrol and tyrosol revert H2O2 production induced by oxLDL as well as AA release and PGE2 synthesis and that these effects were not as a consequence of these compounds interfering with the oxLDL binding to their receptors. Interestingly, beta-sitosterol presence enhances these polyphenol actions. Thus, we found a synergistic action of polyphenols of olive oil and wine and beta-sitosterol of olive oil led to the modulation of the effects of oxLDL on oxidative stress and PGE2 synthesis.

In vitro antioxidant properties, free radicals scavenging activities of extracts and polyphenol composition of a non-timber forest product used as spice: Monodora myristica.

PubMed

Moukette, Bruno Moukette; Pieme, Constant Anatole; Njimou, Jacques Romain; Biapa, Cabral Prosper Nya; Marco, Bravi; Ngogang, Jeanne Yonkeu

2015-03-14

Excessive production of free radicals causes direct damage to biological molecules such as DNA, proteins, lipids, carbohydrates leading to tumor development and progression. Natural antioxidant molecules from phytochemicals of plant origin may directly inhibit either their production or limit their propagation or destroy them to protect the system. In the present study, Monodora myristica a non-timber forest product consumed in Cameroon as spice was screened for its free radical scavenging properties, antioxidant and enzymes protective activities. Its phenolic compound profile was also realized by HPLC. This study demonstrated that M. myristica has scavenging properties against DPPH(•), OH(•), NO(•), and ABTS(•) radicals which vary in a dose depending manner. It also showed an antioxidant potential that was comparable with that of Butylated Hydroxytoluene (BHT) and vitamin C used as standard. The aqueous ethanol extract of M. myristica barks (AEH); showed a significantly higher content in polyphenolic compounds (21.44 ± 0.24 mg caffeic acid/g dried extract) and flavonoid (5.69 ± 0.07 quercetin equivalent mg/g of dried weight) as compared to the other studied extracts. The HPLC analysis of the barks and leaves revealed the presence of several polyphenols. The acids (3,4-OH-benzoic, caffeic, gallic, O- and P- coumaric, syringic, vanillic), alcohols (tyrosol and OH-tyrosol), theobromine, quercetin, rutin, catechine and apigenin were the identified and quantified polyphenols. All the tested extracts demonstrated a high protective potential on the superoxide dismutase (SOD), catalase and peroxidase activities. Finally, the different extracts from M. myristica and specifically the aqueous ethanol extract reveal several properties such as higher free radical scavenging properties, significant antioxidant capacities and protective potential effects on liver enzymes.

Diversity and antioxidant activity of culturable endophytic fungi from alpine plants of Rhodiola crenulata, R. angusta, and R. sachalinensis.

PubMed

Cui, Jin-Long; Guo, Ting-Ting; Ren, Zhen-Xing; Zhang, Na-Sha; Wang, Meng-Liang

2015-01-01

Rhodiola spp. are rare and endangered alpine plants widely used as medicines and food additives by many civilizations since ancient times. Their main effective ingredients (such as salidroside and p-tyrosol) are praised to exhibit pharmacologic effects on high-altitude sickness and possess anti-aging and other adaptogenic capacities based on their antioxidant properties. In this study, 347 endophytic fungi were isolated from R. crenulata, R. angusta, and R. sachalinensis, and the molecular diversity and antioxidant activities of these fungi were investigated for the first time. These fungi were categorized into 180 morphotypes based on cultural characteristics, and their rRNA gene ITS sequences were analyzed by BLAST search in the GenBank database. Except for 12 unidentified fungi (6.67%), all others were affiliated to at least 57 genera in 20 orders of four phyla, namely, Ascomycota (88.89%), Basidiomycota (2.78%), Zygomycota (1.11%), and Glomeromycota (0.56%), which exhibited high abundance and diversity. Antioxidant assay showed that the DPPH radical-scavenging rates of 114 isolates (63.33%) were >50%, and those of five isolates (Rct45, Rct63, Rct64, Rac76, and Rsc57) were >90%. The EC50 values of five antioxidant assays suggested significant potential of these fungi on scavenging DPPH•, O2-•, and OH• radicals, as well as scavenging nitrite and chelating Fe2+, which showed preference and selection between endophytic fungi and their hosts. Further research also provided the first evidence that Rac12 could produce salidrosides and p-tyrosol. Results suggested that versatile endophytic fungi associated with Rhodiola known as antioxidants could be exploited as potential sources of novel antioxidant products.

Nutritional attributes of ash (Fraxinus spp.) outer bark and phloem and their relationships to resistance against the emerald ash borer.

PubMed

Hill, Amy L; Whitehill, Justin G A; Opiyo, Stephen O; Phelan, P Larry; Bonello, Pierluigi

2012-12-01

The emerald ash borer (Agrilus planipennis Fairmaire, EAB) is an alien, invasive wood-boring insect that is responsible for killing millions of ash trees since its discovery in North America in 2002. All North American ash species (Fraxinus spp.) that EAB has encountered have shown various degrees of susceptibility, while Manchurian ash (Fraxinus mandshurica Ruprecht), which shares a co-evolutionary history with this insect, is resistant. Recent studies have looked into constitutive resistance mechanisms in Manchurian ash, concentrating on the secondary phloem, which is the feeding substrate for the insect. In addition to specialized metabolism and defense-related components, primary metabolites and nutritional summaries can also be important to understand the feeding behavior of insect herbivores. Here, we have compared the nutritional characteristics (water content, total protein, free amino acids, total soluble sugars and starch, percent carbon and nitrogen, and macro- and micronutrients) of outer bark and phloem from black, green, white and Manchurian ash to determine their relevance to resistance or susceptibility to EAB. Water content and concentrations of Al, Ba, Cu, Fe, K, Li, tryptophan and an unknown compound were found to separate black and Manchurian ash from green and white ash in a principal component analysis (PCA), confirming their phylogenetic placements into two distinct clades. The traits that distinguished Manchurian ash from black ash in the PCA were water content and concentrations of total soluble sugars, histidine, lysine, methionine, ornithine, proline, sarcosine, tyramine, tyrosol, Al, Fe, K, Na, V and an unknown compound. However, only proline, tyramine and tyrosol were significantly different, and higher, in Manchurian ash than in black ash.

Candida krusei form mycelia along agar surfaces towards each other and other Candida species.

PubMed

Fleischmann, Jacob; Broeckling, Corey D; Lyons, Sarah

2017-03-11

Candida krusei has been known to exhibit communal interactions such as pellicle formation and crawling out of nutritional broth. We noticed another possible interaction on agar surfaces, where C. krusei yeast cells formed mycelia along agar surfaces toward each other. We report here the results of experiments to study this interaction. When C.krusei yeast cells are plated in parallel streaks, they form mycelia along agar surfaces toward other yeasts. They also detect the presence of Candida albicans and Candida glabrata across agar surfaces, while the latter two react neither to their own kind, nor to C. krusei. Secreted molecule(s) are likely involved as C.krusei does not react to heat killed C. krusei. Timing and rate of mycelia formation across distances suggests that mycelia start forming when a secreted molecule(s) on agar surface reaches a certain concentration. We detected farnesol, tyrosol and tryptophol molecules that may be involved with mycelial formation, on the agar surfaces between yeast streaks. Unexpectedly the amounts detected between streaks were significantly higher than would have expected from additive amounts of two streaks. All three Candida species secreted these molecules. When tested on agar surface however, none of these molecules individually or combined induced mycelia formation by C. krusei. Our data confirms another communal interaction by C. krusei, manifested by formation of mycelia by yeast cells toward their own kind and other yeasts on agar surfaces. We detected secretion of farnesol, tyrosol and tryptophol by C. krusei but none of these molecules induced this activity on agar surface making it unlikely that they are the ones utilized by this yeast for this activity.

Role of nutraceutical SIRT1 modulators in AMPK and mTOR pathway: Evidence of a synergistic effect.

PubMed

Giovannini, Luca; Bianchi, Sara

2017-02-01

The aim of this study was to evaluate the effect of different natural substances on SIRT1 expression and on AMPK and mTOR phosphorylation. Moreover, we investigated the presence of a synergistic effect between the substances. Human cervical carcinoma cells were seeded in 12-well plates, then incubated with the nine tested substances (resveratrol, quercetin, berberine, catechin, tyrosol, ferulic acid, niclosamide, curcumin, and malvidin) at different concentrations and left in incubation for 3, 6, and 24 h. The targeting proteins' expression and phosphorylation were evaluated by immunoblotting, and cytotoxicity tests were performed by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (P > 0.05) in the number of viable cells was found. The expression of SIRT1 was significantly increased in all experimental groups compared with the control group (P < 0.001). Instead, the simultaneous administration involved a significant and synergistic increase in the expression of SIRT1 for some but not all of the tested compounds. Finally, the individual administration of berberine, quercetin, ferulic acid, and tyrosol resulted in a statistically significant increase in AMPK activation and mTOR inhibition, whereas their associated administration did not reveal a synergistic effect. Our results provide evidence that all compounds have the potential to stimulate SIRT1 and sustain the stimulating action of resveratrol on SIRT1, already widely reported in the literature. In this regard, we confirm the interaction of these substances also with the pathway of AMPK and mTOR, in support of the studies that highlight the importance of SIRT1/AMPK and mTOR pathway in many diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between Polyphenol Intake and Hypertension in Adults and Older Adults: A Population-Based Study in Brazil

PubMed Central

Miranda, Andreia Machado; Steluti, Josiane; Fisberg, Regina Mara; Marchioni, Dirce Maria

2016-01-01

Background/Objective Hypertension is an important risk factor for cardiovascular disease, and diet has been identified as a modifiable factor for preventing and controlling hypertension. Besides, epidemiological studies have suggested an inverse association between polyphenol intake and cardiovascular diseases. The aim of this study was to evaluate the association between the intake of polyphenols and hypertension in a general population of Sao Paulo. Methods Data came from the ‘Health Survey of Sao Paulo (ISA-Capital)’ among 550 adults and older adults in Sao Paulo, Brazil. Diet was assessed by two 24-hour dietary recalls (24HR). Usual intakes were calculated using the Multiple Source Method. Polyphenol intake was calculated by matching food consumption data from the 24HR with the Phenol-Explorer database. The associations between the hypertension and tertiles of the total and classes of polyphenols intake were tested by multivariate logistic regression analysis. Results After multivariate adjustment for potential confounding factors the findings showed an inverse and linearly association between the hypertension and highest tertiles of tyrosols (OR = 0.33; 95%CI 0.18, 0.64), alkylphenols (OR = 0.45; 95%CI 0.23, 0.87), lignans (OR = 0.49; 95%CI 0.25, 0.98), as well as stilbenes (OR = 0.60; 95%CI 0.36, 0.98), and other polyphenols (OR = 0.33; 95%CI 0.14, 0.74). However, total polyphenol intake, and phenolic acids were significantly associated only in the middle tertile with hypertension and flavonoids were not significant associated. Conclusion There is an inverse and linearly association between the highest tertile of some classes of polyphenols, such as, tyrosols, alkylphenols, lignans, stilbenes, other polyphenols and hypertension. PMID:27792767

[A new secoiridoid from the flowers of Jasminum officinale L. var. grandiflorum].

PubMed

Zhao, Gui-Qin; Yin, Zhi-Feng; Dong, Jun-Xing

2008-05-01

To study the chemical constituents of the flowers of Jasminum officinale L. var. grandiflorum, the compounds were isolated and purified by HPLC, recrystallization and chromatography on silica gel and Sephadex LH-20 column. Their structures were elucidated on the basis of physicochemical properties and spectral analysis. Six secoiridoids were identified as jasgranoside (I), jaspolyoside (II), 8-epi-kingiside (III), 10-hydroxy-oleuropein (IV), 10-hydroxy-ligstroside (V), oleoside-7, 11-dimethyl ester (VI). Compound I is a new compound. Compounds II, III, IV, V and VI were isolated from Jasminum officinale L. var. grandiflorum for the first time.

Screening and identification of three typical phenylethanoid glycosides metabolites from Cistanches Herba by human intestinal bacteria using UPLC/Q-TOF-MS.

PubMed

Li, Yang; Zhou, Guisheng; Peng, Ying; Tu, Pengfei; Li, Xiaobo

2016-01-25

Acteoside, isoacteoside, and 2'-acetylacteoside are three representative phenylethanoid glycosides (PhGs), which are widely distributed in many plants and also known as the active components of Cistanches Herba. However, the extremely low oral bioavailability of acteoside in rats implies that these structural similar components may go through multiple sequential routes of hydrolysis in gastrointestinal tract before they are absorbed into blood. Therefore, the metabolites of these three components and other PhGs from gastrointestinal tract such as echinacoside, are supposed to be the bioactive elements. In this study, we established an approach combining ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) with MS(E) technology and MetaboLynx™ software for the rapid metabolic profiling of acteoside, isoacteoside, and 2'-acetylacteoside by human intestinal bacteria. As a result, 11 metabolites of acteoside, 7 metabolites of isoacteoside, and 11 metabolites of 2'-acetylacteoside were identified respectively. 8 metabolic pathways including deglycosylation, de-rhamnose, de-hydroxytyrosol, de-caffeoyl, deacetylation, reduction, acetylation, and sulfate conjugation were proposed to involve in the generation of these metabolites. Furthermore, we found that the degraded metabolites hydroxytyrosol (HT) and 3-hydroxyphenylpropionic (3-HPP) were transformed from acteoside, isoacteoside, and 2'-acetylacteoside by human intestinal bacteria and demonstrated similar bioactivities to their precursors. These findings are significant for our understanding of the metabolism of PhGs and the proposed metabolic pathways of bioactive components might be crucial for further pharmacokinetic evaluations of Cistanches Herba. Copyright © 2015 Elsevier B.V. All rights reserved.

Extra Virgin Olive Oil Reduced Polyunsaturated Fatty Acid and Cholesterol Oxidation in Rodent Liver: Is This Accounted for Hydroxytyrosol-Fatty Acid Conjugation?

PubMed

Lee, Yiu Yiu; Crauste, Céline; Wang, Hualin; Leung, Ho Hang; Vercauteren, Joseph; Galano, Jean-Marie; Oger, Camille; Durand, Thierry; Wan, Jennifer Man-Fan; Lee, Jetty Chung-Yung

2016-10-17

The effects of extra virgin olive oil (EVOO) and carbon tetrachloride (CCl 4 ) induced oxidative stress in rats were determined by the generation of isoprostanoids. These are known to be robust biomarkers to evaluate nonenzymatic and free radical related oxidation. Other oxidative stress biomarkers such as hydroxyeicosatetraenoic acid products (HETEs) and cholesterol oxidation products (COPs) were also determined. The rodents received a control diet, high-fat diet (20% w/w) composed of extra virgin olive oil (EVOO), corn oil (CO), or lard, and high-fat diets with CCl 4 insult throughout the experimental period. The EVOO diet was found to suppress the formation of isoprostanoids and COPs compared to that of the control. EVOO also had a high total phenolic content and antioxidant activity compared to those of CO and lard and may be contributed to by the hydroxytyrosol component conjugated to fatty acids (HT-FA). This is the first study to identify HT-FA in EVOO, and it was 4-fold higher than that of olive oil, whereas none was found in corn oil. Furthermore, the EVOO diet showed reduced liver lipid vesicles in CCl 4 treated rats compared to that of the control. However, liver toxicity measurements of AST (aspartate transaminase) and ALT (alanine transaminase) activities showed augmentation with CCl 4 treatment but were not alleviated by the diets given. Our findings suggest that EVOO is a daily functional food capable of enhancing the antioxidant system for liver protection; the effect is potentially attributed to the phenolic and lipophenolic (phenol conjugated by fatty acids) content.

Assessment of the antioxidant activity of an olive oil total polyphenolic fraction and hydroxytyrosol from a Greek Olea europea variety in endothelial cells and myoblasts

PubMed Central

Kouka, Paraskevi; Priftis, Alexandros; Stagos, Dimitrios; Angelis, Apostolis; Stathopoulos, Panagiotis; Xinos, Nikos; Skaltsounis, Alexios-Léandros; Mamoulakis, Charalampos; Tsatsakis, Aristides M.; Spandidos, Demetrios A.; Kouretas, Demetrios

2017-01-01

Olive oil (OO) constitutes the basis of the Mediterranean diet, and it seems that its biophenols, such as hydroxytyrosol (HT) may scavenge free radicals, attracting distinct attention due to their beneficial effects in many pathological conditions, such as cancer. To the best of our knowedge, this is the first study in which the functional properties of an OO total polyphenolic fraction (TPF) and pure HT were examined in order to determine their antioxidant effects at a cellular level in endothelial cells and myoblasts. The test compounds were isolated using a green gradient-elution centrifugal partition chromatography-based method that allows the isolation of large volumes of OO in a continuous extraction procedure and with extremely low solvent consumption. For the isolation of HT, a combination of two chromatographic techniques was used, which is effective for the recovery of pure compounds from complex natural extracts. Moreover, TPF and HT exhibited potent free radical scavenging activity in vitro. The cells were treated with non-cytotoxic concentrations and their redox status [in terms of glutathione (GSH) and reactive oxygen species (ROS) levels] was assessed. TPF extract was less cytotoxic than HT, and the observed differences between the two cell lines used suggest a tissue-specific activity. Finally, flow cytometric analysis revealed that both TPF and HT improved the redox status by increasing the levels of GSH, one of the most important antioxidant molecules, in both endothelial cells and myoblasts, while the ROS levels were not significantly affected. PMID:28731131

Assessment of the antioxidant activity of an olive oil total polyphenolic fraction and hydroxytyrosol from a Greek Olea europea variety in endothelial cells and myoblasts.

PubMed

Kouka, Paraskevi; Priftis, Alexandros; Stagos, Dimitrios; Angelis, Apostolis; Stathopoulos, Panagiotis; Xinos, Nikos; Skaltsounis, Alexios-Léandros; Mamoulakis, Charalampos; Tsatsakis, Aristides M; Spandidos, Demetrios A; Kouretas, Demetrios

2017-09-01

Olive oil (OO) constitutes the basis of the Mediterranean diet, and it seems that its biophenols, such as hydroxytyrosol (HT) may scavenge free radicals, attracting distinct attention due to their beneficial effects in many pathological conditions, such as cancer. To the best of our knowedge, this is the first study in which the functional properties of an OO total polyphenolic fraction (TPF) and pure HT were examined in order to determine their antioxidant effects at a cellular level in endothelial cells and myoblasts. The test compounds were isolated using a green gradient‑elution centrifugal partition chromatography‑based method that allows the isolation of large volumes of OO in a continuous extraction procedure and with extremely low solvent consumption. For the isolation of HT, a combination of two chromatographic techniques was used, which is effective for the recovery of pure compounds from complex natural extracts. Moreover, TPF and HT exhibited potent free radical scavenging activity in vitro. The cells were treated with non‑cytotoxic concentrations and their redox status [in terms of glutathione (GSH) and reactive oxygen species (ROS) levels] was assessed. TPF extract was less cytotoxic than HT, and the observed differences between the two cell lines used suggest a tissue‑specific activity. Finally, flow cytometric analysis revealed that both TPF and HT improved the redox status by increasing the levels of GSH, one of the most important antioxidant molecules, in both endothelial cells and myoblasts, while the ROS levels were not significantly affected.

Antioxidant activity of olive wine, a byproduct of olive mill wastewater.

PubMed

Yao, Qian; He, Gang; Guo, Xiaoqiang; Hu, Yibing; Shen, Yuanfu; Gou, Xiaojun

2016-10-01

Context Although olive mill wastewater (OMWW) is a good source of bioactive phenolic compounds, disposing OMWW is a serious environmental challenge. Production of wine via fermenting OMWW may be a promising alternative to deal with OMWW. However, whether or not olive wine from OMWW still reserves its original bioactivities remains unclear. Objective This study examines antioxidant activity of olive wine fermented from OMWW. Materials and methods Hydroxytyrosol in olive oil was determined by HPLC. Total flavonoid, total polyphenol and in vitro antioxidant activities were measured by spectrophotometry. Aged mice were intragastricly administered 7, 14 and 28 mL/kg olive wine consecutively for 30 d. Afterward, levels of malonaldehyde (MDA), protein carbonyl, reduced glutathione (GSH) and activity of superoxide dismutase (SOD) were assayed in mouse plasma and liver. Results Contents of hydroxytyrosol, total flavonoid and total polyphenol in olive wine were 0.14 ± 0.01, 0.29 ± 0.06 and 0.43 ± 0.03 mg/mL, respectively. The IC50 value of olive wine to scavenge DPPH and hydroxyl free radicals was 2.5% and 3.2% (v/v), respectively. Compared with the solvent control group, olive wine with a dose of 28 mL/kg remarkably lowered mouse MDA concentration in liver, and reduced protein carbonyl level in plasma (p < 0.05). Meanwhile, olive wine at doses of 7 and 28 mL/kg notably enhanced SOD activity in both mouse plasma and liver (p < 0.05). The beneficial effect on liver was superior to that of γ-tocopherol. Conclusion The study demonstrated that olive wine from OMWW has potential for treating oxidative stress-associated diseases.

Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice.

PubMed

Cao, Ke; Xu, Jie; Zou, Xuan; Li, Yuan; Chen, Cong; Zheng, Adi; Li, Hao; Li, Hua; Szeto, Ignatius Man-Yau; Shi, Yujie; Long, Jiangang; Liu, Jiankang; Feng, Zhihui

2014-02-01

A Mediterranean diet rich in olive oil has profound influence on health outcomes including metabolic syndrome. However, the active compound and detailed mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic compound in virgin olive oil, has received increased attention for its antioxidative activity and regulation of mitochondrial function. Here, we investigated whether HT is the active compound in olive oil exerting a protective effect against metabolic syndrome. In this study, we show that HT could prevent high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress by enhancing antioxidant enzyme activities, normalize expression of mitochondrial complex subunits and mitochondrial fission marker Drp1, and eventually inhibit apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial carbonyl protein were decreased and mitochondrial complex activities were significantly improved by HT supplementation. In db/db mice, HT significantly decreased fasting glucose, similar to metformin. Notably, HT decreased serum lipid, at which metformin failed. Also, HT was more effective at decreasing the oxidation levels of lipids and proteins in both liver and muscle tissue. Similar to the results in the HFD model, HT decreased muscle mitochondrial carbonyl protein levels and improved mitochondrial complex activities in db/db mice. Our study links the olive oil component HT to diabetes and metabolic disease through changes that are not limited to decreases in oxidative stress, suggesting a potential pharmaceutical or clinical use of HT in metabolic syndrome treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Silicon vs. Hydroxytyrosol-Enriched Restructured Pork on Liver Oxidation Status of Aged Rats Fed High-Saturated/High-Cholesterol Diets.

PubMed

Santos-López, Jorge A; Garcimartín, Alba; Merino, Pinar; López-Oliva, M Elvira; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J

2016-01-01

Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH.

Involvement of bilitranslocase and beta-glucuronidase in the vascular protection by hydroxytyrosol and its glucuronide metabolites in oxidative stress conditions.

PubMed

Peyrol, Julien; Meyer, Grégory; Obert, Philippe; Dangles, Olivier; Pechère, Laurent; Amiot, Marie-Josèphe; Riva, Catherine

2018-01-01

Olive oil vascular benefits have been attributed to hydroxytyrosol (HT). However, HT biological actions are still debated because it is extensively metabolized into glucuronides (GCs). The aim of this study was to test HT and GC vasculoprotective effects and the underlying mechanisms using aorta rings from 8-week-old male Wistar rats. In the absence of oxidative stress, incubation with 100 μM HT or GC for 5 min did not exert any vasorelaxing effect and did not influence the vascular function. Conversely, in condition of oxidative stress [upon incubation with 500 μM tert-butylhydroperoxide (t-BHP) for 30 min], preincubation with HT or GC improved acetylcholine-induced vasorelaxation compared with untreated samples (no t-BHP). This protective effect was lost for GC, but not for HT, when a washing step (15 min) was introduced between preincubation with HT or GC and t-BHP addition, suggesting that only HT enters the cells. In agreement, bilitranslocase inhibition with 100 μM phenylmethanesulfonyl fluoride for 20 min reduced significantly HT, but not GC, effect on the vascular function upon stress induction. Moreover, GC protective effect (improvement of endothelium-dependent relaxation in response to acetylcholine) in oxidative stress conditions was reduced by preincubation of aorta rings with 300 μM D-saccharolactone to inhibit β-glucuronidase, which can deconjugate polyphenols. Finally, only HT was detected by high-pressure liquid chromatography in aorta rings incubated with GC and t-BHP. These results suggest that, in conditions of oxidative stress, GC can be deconjugated into HT that is transported through the cell membrane by bilitranslocase to protect vascular function. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Silicon vs. Hydroxytyrosol-Enriched Restructured Pork on Liver Oxidation Status of Aged Rats Fed High-Saturated/High-Cholesterol Diets

PubMed Central

Merino, Pinar; López-Oliva, M. Elvira; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J.

2016-01-01

Background Pork is an essential component of the diet that has been linked with major degenerative diseases and development of non-alcoholic steatohepatitis (NASH). Previous studies have. Previous studies have demonstrated the in vitro antioxidant activity of silicon (Si). Furthermore, when Si is added to restructured pork (RP) strongly counterbalances the negative effect of high-cholesterol-ingestion, acting as an active hypocholesterolemic and hypolipemic dietary ingredient in aged rats. Objective This study was designed to evaluate the effects of Si vs hydroxytyrosol (HxT) RP on liver antioxidant defense in aged rats fed cholesterol-enriched high saturated/high cholesterol diets as a NASH model. Methods Four diets were prepared: Control RP diet (C) with non-added cholesterol; Cholesterol-enriched high-saturated/high-cholesterol control RP diet (CHOL-C) with added cholesterol and cholic acid; Si- or HxT-RP cholesterol-enriched high-saturated/high-cholesterol diets (CHOL-Si and CHOL-HxT). Groups of six male Wistar rats (1-yr old) were fed these modified diets for eight weeks. Total cholesterol, hepatosomatic index, liver Nrf2 and antioxidant (CAT, SOD, GSH, GSSG, GR, GPx) markers were determined. Results Both CHOL-Si and CHOL-HxT diets enhanced the liver antioxidant status, reduced hepatosomatic index and increased SOD actvity. Hydrogen peroxide removal seemed to be involved, explaining that the value of redox index was even lower than C without changing the CAT activity. CHOL-Si results were quite better than CHOL-HxT in most measured parameters. Conclusions Our study suggests that Si incorporated into RP matrix was able to counterbalance, more efficiently than HxT, the deleterious effect of consuming a high-saturated/high-cholesterol diet, by improving the liver antioxidant defenses in the context of NASH. PMID:26807847

Degradation of tyrosol by a novel electro-Fenton process using pyrite as heterogeneous source of iron catalyst.

PubMed

Ammar, Salah; Oturan, Mehmet A; Labiadh, Lazhar; Guersalli, Amor; Abdelhedi, Ridha; Oturan, Nihal; Brillas, Enric

2015-05-01

Tyrosol (TY) is one of the most abundant phenolic components of olive oil mill wastewaters. Here, the degradation of synthetic aqueous solutions of 0.30 mM TY was studied by a novel heterogeneous electro-Fenton (EF) process, so-called EF-pyrite, in which pyrite powder was the source of Fe(2+) catalyst instead of a soluble iron salt used in classical EF. Experiments were performed with a cell equipped with a boron-doped diamond anode and a carbon-felt cathode, where TY and its products were destroyed by hydroxyl radicals formed at the anode surface from water oxidation and in the bulk from Fenton's reaction between Fe(2+) and H2O2 generated at the cathode. Addition of 1.0 g L(-1) pyrite provided an easily adjustable pH to 3.0 and an appropriate 0.20 mM Fe(2+) to optimize the EF-pyrite treatment. The effect of current on mineralization rate, mineralization current efficiency and specific energy consumption was examined under comparable EF and EF-pyrite conditions. The performance of EF-pyrite was 8.6% superior at 50 mA due to self-regulation of soluble Fe(2+) by pyrite. The TY decay in this process followed a pseudo-first-order kinetics. The absolute rate constant for TY hydroxylation was 3.57 × 10(9) M(-1) s(-1), as determined by the competition kinetics method. Aromatic products like 3,4-dihydroxyphenylethanol, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid and catechol, as well as o-benzoquinone, were identified by GC-MS and reversed-phase HPLC. Short-chain aliphatic carboxylic acids like maleic, glycolic, acetic, oxalic and formic were quantified by ion-exclusion HPLC. Oxalic acid was the major and most persistent product found. Based on detected intermediates, a plausible mineralization pathway for TY by EF-pyrite was proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multicommuted flow injection method for fast photometric determination of phenolic compounds in commercial virgin olive oil samples.

PubMed

Lara-Ortega, Felipe J; Sainz-Gonzalo, Francisco J; Gilbert-López, Bienvenida; García-Reyes, Juan F; Molina-Díaz, Antonio

2016-01-15

A multicommuted flow injection method has been developed for the determination of phenolic species in virgin olive oil samples. The method is based on the inhibitory effect of antioxidants on a stable and colored radical cation formation from the colorless compound N,N-dimethyl-p-phenylenediamine (DMPD(•+)) in acidic medium in the presence of Fe(III) as oxidant. The signal inhibition by phenolic species and other antioxidants is proportional to their concentration in the olive oil sample. Absorbance was recorded at 515nm by means of a modular fiber optic spectrometer. Oleuropein was used as the standard for phenols determination and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) was the reference standard used for total antioxidant content calculation. Linear response was observed within the range of 250-1000mg/kg oleuropein, which was in accordance with phenolic contents observed in commercial extra virgin olive oil in the present study. Fast and low-volume liquid-liquid extraction of the samples using 60% MeOH was made previous to their insertion in the flow multicommuted system. The five three-way solenoid valves used for multicommuted liquid handling were controlled by a homemade electronic interface and Java-written software. The proposed approach was applied to different commercial extra virgin olive oil samples and the results were consistent with those obtained by the Folin Ciocalteu (FC) method. Total time for the sample preparation and the analysis required in the present approach can be drastically reduced: the throughput of the present analysis is 8 samples/h in contrast to 1sample/h of the conventional FC method. The present method is easy to implement in routine analysis and can be regarded as a feasible alternative to FC method. Copyright © 2015 Elsevier B.V. All rights reserved.

Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients

PubMed Central

Larussa, Tiziana; Oliverio, Manuela; Suraci, Evelina; Greco, Marta; Placida, Roberta; Gervasi, Serena; Marasco, Raffaella; Imeneo, Maria; Paolino, Donatella; Tucci, Luigi; Gulletta, Elio; Fresta, Massimo; Procopio, Antonio; Luzza, Francesco

2017-01-01

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC. PMID:28420140

Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients.

PubMed

Larussa, Tiziana; Oliverio, Manuela; Suraci, Evelina; Greco, Marta; Placida, Roberta; Gervasi, Serena; Marasco, Raffaella; Imeneo, Maria; Paolino, Donatella; Tucci, Luigi; Gulletta, Elio; Fresta, Massimo; Procopio, Antonio; Luzza, Francesco

2017-04-15

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 μg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC.

Oleuropein inhibits the IL-1β-induced expression of inflammatory mediators by suppressing the activation of NF-κB and MAPKs in human osteoarthritis chondrocytes.

PubMed

Feng, Zhenhua; Li, Xiaobin; Lin, Jian; Zheng, Wenhao; Hu, Zhichao; Xuan, Jiangwei; Ni, Wenfei; Pan, Xiaoyun

2017-10-18

Osteoarthritis (OA) is the most common form of joint disease and is widespread in the elderly population and is characterized by erosion of articular cartilage, subchondral bone sclerosis and synovitis. Oleuropein (OL), a secoiridoid, is considered as the most prevalent phenolic component in olive leaves and seeds, pulp and peel of unripe olives and has been shown to have potent anti-inflammatory effects. However, its effects on OA have not been clearly elucidated. This study aimed to assess the effect of OL on human OA chondrocytes. Human OA chondrocytes were pretreated with OL (10, 50 and 100 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. The production of NO, PGE2, MMP-1, MMP-13, and ADAMTS-5 was evaluated by the Griess reaction and ELISA assays. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP13, ADAMTS-5, aggrecan, and collagen-II was measured by using real-time PCR. The protein expressions of COX-2, iNOS, p65, IκB-α, JNK, p-JNK, ERK, p-ERK, p38, and p-p38 were tested by using western blot. We found that OL significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-13, and ADAMTS-5; and degradation of aggrecan and collagen-II. Furthermore, OL dramatically suppressed IL-1β-stimulated NF-κB and MAPK activation. Immunofluorescence staining demonstrated that OL could suppress IL-1β-induced phosphorylation of p65 nuclear translocation. These results indicate that the therapeutic effect of OL on OA is accomplished through the inhibition of both NF-κB and MAPK signaling pathways. Altogether, our findings provide the evidence to develop OL as a potential therapeutic agent for patients with OA.

Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology

PubMed Central

Pantano, Daniela; Luccarini, Ilaria; Nardiello, Pamela; Servili, Maurizio; Stefani, Massimo

2016-01-01

Aim In TgCRND8 (Tg) mice we checked the dose–response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg kg−1 of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg kg−1 of diet) previously investigated. Methods Four month‐old Tg mice were equally divided into four groups and treated for 8 weeks with a modified low fat (5.0%) AIN‐76 A diet (10 g day−1 per mouse) as such, supplemented with OLE (12.5 or 0.5 mg kg−1 of diet) or with a mix of polyphenols (50 mg kg−1 of diet) found in olive mill waste water. Behavioural performance was evaluated by the step down inhibitory avoidance and object recognition tests. Neuropathology was analyzed by immunohistochemistry. Results OLE supplementation at 12.5 mg kg−1 of diet and the mix of polyphenols was found to improve significantly cognitive functions of Tg mice (P < 0.0001). Aß42 and pE‐3Aß plaque area and number were significantly reduced in the cortex by OLE and in the cortex and hippocampus by the mix of polyphenols (P < 0.01, P < 0.001 and P < 0.0001). Similar autophagy induction was found in the brain cortex of differently treated mice. Conclusion Our results extend previous data showing that the effects of OLE on behavioural performance and neuropathology are dose‐dependent and not closely related to OLE by itself. In fact, diet supplementation with the same dose of a mix of polyphenols found in olive mill waste water resulted in comparable neuroprotection. PMID:27131215

Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology.

PubMed

Pantano, Daniela; Luccarini, Ilaria; Nardiello, Pamela; Servili, Maurizio; Stefani, Massimo; Casamenti, Fiorella

2017-01-01

In TgCRND8 (Tg) mice we checked the dose-response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg kg -1 of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg kg -1 of diet) previously investigated. Four month-old Tg mice were equally divided into four groups and treated for 8 weeks with a modified low fat (5.0%) AIN-76 A diet (10 g day -1  per mouse) as such, supplemented with OLE (12.5 or 0.5 mg kg -1 of diet) or with a mix of polyphenols (50 mg kg -1 of diet) found in olive mill waste water. Behavioural performance was evaluated by the step down inhibitory avoidance and object recognition tests. Neuropathology was analyzed by immunohistochemistry. OLE supplementation at 12.5 mg kg -1 of diet and the mix of polyphenols was found to improve significantly cognitive functions of Tg mice (P < 0.0001). Aß42 and pE-3Aß plaque area and number were significantly reduced in the cortex by OLE and in the cortex and hippocampus by the mix of polyphenols (P < 0.01, P < 0.001 and P < 0.0001). Similar autophagy induction was found in the brain cortex of differently treated mice. Our results extend previous data showing that the effects of OLE on behavioural performance and neuropathology are dose-dependent and not closely related to OLE by itself. In fact, diet supplementation with the same dose of a mix of polyphenols found in olive mill waste water resulted in comparable neuroprotection. © 2016 The British Pharmacological Society.

Olea europaea L. leaf extract and derivatives: antioxidant properties.

PubMed

Briante, Raffaella; Patumi, Maurizio; Terenziani, Stefano; Bismuto, Ettore; Febbraio, Ferdinando; Nucci, Roberto

2002-08-14

This paper reports a very simple and fast method to collect eluates with high amounts of hydroxytyrosol, biotransforming Olea europaea L. leaf extract by a thermophilic beta-glycosidase immobilized on chitosan. Some phenolic compounds in the leaf tissue and in the eluates obtained by biotransformation are identified. To propose the eluates as natural substances from a vegetal source, their antioxidant properties have been compared with those of the leaf extract from which they are originated. The eluates possess a higher concentration of simple phenols, characterized by a stronger antioxidant capacity, than those available in extra virgin olive oils and in many tablets of olive leaf extracts, commercially found as dietetic products and food integrators.

Inhibitory effect of trichodermanone C, a sorbicillinoid produced by Trichoderma citrinoviride associated to the green alga Cladophora sp., on nitrite production in LPS-stimulated macrophages.

PubMed

Marra, Roberta; Nicoletti, Rosario; Pagano, Ester; DellaGreca, Marina; Salvatore, Maria Michela; Borrelli, Francesca; Lombardi, Nadia; Vinale, Francesco; Woo, Sheridan L; Andolfi, Anna

2018-05-31

From the green alga Cladophora sp. collected in Italy, the marine fungal strain A12 of Trichoderma citrinoviride was isolated, identified and characterized. LC-MS qTOF analysis was applied to perform a metabolic profile of the fungal culture. Chromatographic techniques and spectroscopic methods were used to isolate and characterize the major secondary metabolites produced by this strain in liquid culture. In particular, four known sorbicillinoids (trichodermanone C, spirosorbicillinol A, vertinolide and sorbicillin) were purified and identified, together with 2-phenylethanol and tyrosol. Moreover, metabolomic analysis allowed to detect small amounts of trichodimerol, rezishanone A, 2',3'-dihydrosorbicillin and bisvertinol. For the first time a significant inhibitory effect on nitrite levels has been shown for trichodermanone C in lipopolysaccharide-stimulated J774A.1 macrophages.

[Glycosides from flowers of Jasminum officinale L. var. grandiflorum].

PubMed

Zhao, Gui-qin; Xia, Jing-jing; Dong, Jun-xing

2007-10-01

To study the chemical constituents of the flower of Jasminum officinale L. var. grandiflorum. The compounds were isolated and purified by re-crystallization and chromatography on silica gel and Sephadex LH-20 column. Their structures were elucidated on the physicochemical properties and spectral analysis. Seven glycosides were identified as kaempferol-3-O-alpha-L-rhamnopyranosyl (1-->3)-[alpha-L-rhamnopyranosyl (1-->6)]-beta-D-galactopyranoside (I), kaempferol-3-O-rutinoside (II), 7-ketologanin (III), oleoside-11-methyl ester (IV), 7-glucosyl-l1-methyl oleoside (V), ligstroside (VI), oleuropein (VII). Compound I is a new compound. Compounds III and V were isolated from the family of Jasminum for the first time and compounds II, IV and VI were isolated from Jasminum officinale L. var. grandiflorum for the first time.

Microchannel emulsification: A promising technique towards encapsulation of functional compounds.

PubMed

Khalid, Nauman; Kobayashi, Isao; Neves, Marcos A; Uemura, Kunihiko; Nakajima, Mitsutoshi

2017-06-13

This review provides an overview of microchannel emulsification (MCE) for production of functional monodispersed emulsion droplets. The main emphasis has been put on functional bioactives encapsulation using grooved-type and straight-through microchannel array plates. MCE successfully encapsulates the bioactives like β-carotene, oleuropein, γ-oryzanol, β-sitosterol, L-ascorbic acid and ascorbic acid derivatives, vitamin D and quercetin. These bioactives were encapsulated in a variety of delivery systems like simple and multiple emulsions, polymeric particles, microgels, solid lipid particles and functional vesicles. The droplet generation process in MCE is based upon spontaneous transformation of interfaces rather than high energy shear stress systems. The scale-up of MCE can increase the productivity of monodispersed droplets >100 L h -1 and makes it a promising tool at industrial level.

Phenolic Secoiridoids in Extra Virgin Olive Oil Impede Fibrogenic and Oncogenic Epithelial-to-Mesenchymal Transition: Extra Virgin Olive Oil As a Source of Novel Antiaging Phytochemicals

PubMed Central

Vazquez-Martin, Alejandro; Fernández-Arroyo, Salvador; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Lozano-Sánchez, Jesús; Vellón, Luciano; Micol, Vicente; Joven, Jorge

2012-01-01

Abstract The epithelial-to-mesenchymal transition (EMT) genetic program is a molecular convergence point in the life-threatening progression of organ fibrosis and cancer toward organ failure and metastasis, respectively. Here, we employed the EMT process as a functional screen for testing crude natural extracts for accelerated drug development in fibrosis and cancer. Because extra virgin olive oil (EVOO) (i.e., the juice derived from the first cold pressing of the olives without any further refining process) naturally contains high levels of phenolic compounds associated with the health benefits derived from consuming an EVOO-rich Mediterranean diet, we have tested the ability of an EVOO-derived crude phenolic extract to regulate fibrogenic and oncogenic EMT in vitro. High-performance liquid chromatography (HPLC) coupled to time-of-flight (TOF) mass spectrometry assays revealed that the EVOO phenolic extract was mainly composed (∼70%) of two members of the secoiridoid family of complex polyphenols, namely oleuropein aglycone—the bitter principle of olives—and its derivative decarboxymethyl oleuropein aglycone. EVOO secoiridoids efficiently prevented loss of proteins associated with polarized epithelial phenotype (i.e., E-cadherin) as well as de novo synthesis of proteins associated with mesenchymal migratory morphology of transitioning cells (i.e., vimentin). The ability of EVOO to impede transforming growth factor-β (TGF-β)–induced disintegration of E-cadherin-mediated cell–cell contacts apparently occurred as a consequence of the ability of EVOO phenolics to prevent the upregulation of SMAD4—a critical mediator of TGF-β signaling—and of the SMAD transcriptional cofactor SNAIL2 (Slug)—a well-recognized epithelial repressor. Indeed, EVOO phenolics efficiently prevented crucial TGF-β–induced EMT transcriptional events, including upregulation of SNAI2, TCF4, VIM (Vimentin), FN (fibronectin), and SERPINE1 genes. While awaiting a better mechanistic understanding of how EVOO phenolics molecularly shut down the EMT differentiation process, it seems reasonable to suggest that nontoxic Oleaceae secoiridoids certainly merit to be considered for aging studies and, perhaps, for ulterior design of more pharmacologically active second-generation anti-EMT molecules. PMID:22229524

The Role of Polyphenoloxidase, Peroxidase, and β-Glucosidase in Phenolics Accumulation in Olea europaea L. Fruits under Different Water Regimes

PubMed Central

Cirilli, Marco; Caruso, Giovanni; Gennai, Clizia; Urbani, Stefania; Frioni, Eleonora; Ruzzi, Maurizio; Servili, Maurizio; Gucci, Riccardo; Poerio, Elia; Muleo, Rosario

2017-01-01

Olive fruits and oils contain an array of compounds that contribute to their sensory and nutritional properties. Phenolic compounds in virgin oil and olive-derived products have been proven to be highly beneficial for human health, eliciting increasing attention from the food industry and consumers. Although phenolic compounds in olive fruit and oil have been extensively investigated, allowing the identification of the main classes of metabolites and their accumulation patterns, knowledge of the molecular and biochemical mechanisms regulating phenolic metabolism remains scarce. We focused on the role of polyphenoloxidase (PPO), peroxidase (PRX) and β-glucosidase (β-GLU) gene families and their enzyme activities in the accumulation of phenolic compounds during olive fruit development (35–146 days after full bloom), under either full irrigation (FI) or rain-fed (RF) conditions. The irrigation regime affected yield, maturation index, mesocarp oil content, fruit size, and pulp-to-pit ratio. Accumulation of fruit phenolics was higher in RF drupes than in FI ones. Members of each gene family were developmentally regulated, affected by water regime, and their transcript levels were correlated with the respective enzyme activities. During the early phase of drupe growth (35–43 days after full bloom), phenolic composition appeared to be linked to β-GLU and PRX activities, probably through their effects on oleuropein catabolism. Interestingly, a higher β-GLU activity was measured in immature RF drupes, as well as a higher content of the oleuropein derivate 3,4-DHPEA-EDA and verbascoside. Activity of PPO enzymes was slightly affected by the water status of trees during ripening (from 120 days after full bloom), but was not correlated with phenolics content. Overall, the main changes in phenolics content appeared soon after the supply of irrigation water and remained thereafter almost unchanged until maturity, despite fruit growth and the progressive decrease in pre-dawn leaf water potential. We suggest that enzymes involved in phenolic catabolism in the olive fruit have a differential sensitivity to soil water availability depending on fruit developmental stage. PMID:28536589

Total recovery of the waste of two-phase olive oil processing: isolation of added-value compounds.

PubMed

Fernández-Bolaños, Juan; Rodríguez, Guillermo; Gómez, Esther; Guillén, Rafael; Jiménez, Ana; Heredia, Antonia; Rodríguez, Rocío

2004-09-22

A process for the value addition of solid waste from two-phase olive oil extraction or "alperujo" that includes a hydrothermal treatment has been suggested. In this treatment an autohydrolysis process occurs and the solid olive byproduct is partially solubilized. From this water-soluble fraction can be obtained besides the antioxidant hydroxytyrosol several other compounds of high added value. In this paper three different samples of alperujo were characterized and subjected to a hydrothermal treatment with and without acid catalyst. The main soluble compounds after the hydrolysis were represented by monosaccharides xylose, arabinose, and glucose; oligosaccharides, mannitol and products of sugar destruction. Oligosaccharides were separated by size exclusion chromatography. It was possible to get highly purified mannitol by applying a simple purification method.

Bioactive compounds from Rhodiola rosea (Crassulaceae).

PubMed

Ming, Dong Sheng; Hillhouse, Brian J; Guns, Emma S; Eberding, Andy; Xie, Sherwin; Vimalanathan, Selvarani; Towers, G H Neil

2005-09-01

The methanol extract of the underground part of Rhodiola rosea was found to show inhibitory activity against Staphylococcus aureus. Bioactivity-guided fractionation of a 95% ethanol extract from the stems of R. rosea led to the isolation of five compounds: gossypetin-7-O-L-rhamnopyranoside (1), rhodioflavonoside (2), gallic acid (3), trans-p-hydroxycinnamic acid (4) and p-tyrosol (5). Their structures were elucidated by UV, IR, MS and NMR data, as well as by comparison with those of the literature. Compounds 1 and 2 were evaluated for their antibacterial and antiprostate cancer cell activities. Compounds 1 and 2 exhibited activity against Staphylococcus aureus with minimum inhibitory concentrations of 50 microg/mL and 100 microg/mL, respectively. Cytotoxicity studies of 1 and 2 also displayed activity against the prostate cancer cell line with IC(50) values of 50 microg/mL and 80 microg/mL, respectively. Copyright 2005 John Wiley & Sons, Ltd.

Evaluation of allelopathic, decomposition and cytogenetic activities of Jasminum officinale L. f. var. grandiflorum (L.) Kob. on bioassay plants.

PubMed

Teerarak, Montinee; Laosinwattana, Chamroon; Charoenying, Patchanee

2010-07-01

Methanolic extracts prepared from dried leaves of Jasminum officinale f. var. grandiflorum (L.) Kob. (Spanish jasmine) inhibited seed germination and stunted both root and shoot length of the weeds Echinochloa crus-galli (L.) Beauv. and Phaseolus lathyroides L. The main active compound was isolated and determined by spectral data as a secoiridoid glucoside named oleuropein. In addition, a decrease in allelopathic efficacy appeared as the decomposition periods increased. The mitotic index in treated onion root tips decreased with increasing concentrations of the extracts and longer periods of treatment. Likewise, the mitotic phase index was altered in onion incubated with crude extract. Furthermore, crude extract produced mitotic abnormalities resulting from its action on chromatin organization and mitotic spindle. Copyright (c)2010 Elsevier Ltd. All rights reserved.

Secoiridoids from the stem barks of Fraxinus rhynchophylla with pancreatic lipase inhibitory activity.

PubMed

Ahn, Jong Hoon; Shin, Eunjin; Liu, Qing; Kim, Seon Beom; Choi, Kyeong-Mi; Yoo, Hwan-Soo; Hwang, Bang Yeon; Lee, Mi Kyeong

2013-01-01

Pancreatic lipase digests dietary fats by hydrolysis, which is a key enzyme for lipid absorption. Therefore, reduction of fat absorption by the inhibition of pancreatic lipase is suggested to be a therapeutic strategy for obesity. From the EtOAc-soluble fraction of the stem barks of Fraxinus rhynchophylla (Oleaceae), four secoiridoids such as ligstroside (1), oleuropein (2), 2"-hydroxyoleuropein (3) and hydroxyframoside B (4) were isolated. The inhibitory activity of these compounds on pancreatic lipase was assessed using porcine pancreatic lipase as an in vitro assay system. Compound 4 showed the strongest inhibition on pancreatic lipase, which followed by compounds 1-3. In addition, compound 4 exerted inhibitory effect on pancreatic lipase in a mixed mechanism of competitive and noncompetitive manner. Taken together, F. rhynchophylla and its constituents might be beneficial to obesity.

Dose effect on the uptake and accumulation of hydroxytyrosol and its metabolites in target tissues in rats.

PubMed

López de las Hazas, Maria-Carmen; Rubió, Laura; Kotronoulas, Aristotelis; de la Torre, Rafael; Solà, Rosa; Motilva, Maria-José

2015-07-01

Hydroxytyrosol (HT) is the most prominent phenolic compound of virgin olive oil and due to its scientifically validated biological activities it is entering to the market as a potentially useful supplement for cardiovascular disease prevention. The aim of the present study was to investigate the relationship between the HT dose intake and its tissue uptake in rats, and thus, providing complementary information in relation to the target-dose relationship. Rats were given a refined olive oil enriched with HT at different doses (1, 10, and 100 mg/kg) and they were sacrificed after 5 h to ensure the cell tissue uptake of HT and its metabolites. Plasma samples and different organs as liver, kidney, heart and brain were obtained, and HT metabolites were analyzed by UPLC-MS/MS. The results showed that HT and its metabolites could be accumulated in a dose-dependent manner basically in the liver, kidney, and brain and were detected in these tissues even at nutritionally relevant human doses. The detection of free HT in liver and kidney was noteworthy. To date, this appears to be the only biologically active form, and thus, it provides relevant information for optimizing the potential applications of HT to prevent certain hepatic and renal diseases. In recent years, HT and its derivatives have led to a great interest from the virgin olive oil producers and manufacturers of nutraceutical supplements. The increasing interest in HT is mainly due to the European Food Safety Agency (EFSA) Panel on Dietetic Products, Nutrition, and Allergies (NDA) scientific opinion that established a cause-and-effect relationship between the consumption of olive oil polyphenols and protection of LDL particles from oxidative damage . Based on this positive opinion, the health claim "Olive oil polyphenols contribute to the protection of blood lipids from oxidative stress" was included in the list of health claims , being the only authorized health claim in the European Union regarding polyphenols and health. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mitochondrial dysfunction-associated OPA1 cleavage contributes to muscle degeneration: preventative effect of hydroxytyrosol acetate.

PubMed

Wang, X; Li, H; Zheng, A; Yang, L; Liu, J; Chen, C; Tang, Y; Zou, X; Li, Y; Long, J; Liu, J; Zhang, Y; Feng, Z

2014-11-13

Mitochondrial dysfunction contributes to the development of muscle disorders, including muscle wasting, muscle atrophy and degeneration. Despite the knowledge that oxidative stress closely interacts with mitochondrial dysfunction, the detailed mechanisms remain obscure. In this study, tert-butylhydroperoxide (t-BHP) was used to induce oxidative stress on differentiated C2C12 myotubes. t-BHP induced significant mitochondrial dysfunction in a time-dependent manner, accompanied by decreased myosin heavy chain (MyHC) expression at both the mRNA and protein levels. Consistently, endogenous reactive oxygen species (ROS) overproduction triggered by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), a mitochondrial oxidative phosphorylation inhibitor, was accompanied by decreased membrane potential and decreased MyHC protein content. However, the free radical scavenger N-acetyl-L-cysteine (NAC) efficiently reduced the ROS level and restored MyHC content, suggesting a close association between ROS and MyHC expression. Meanwhile, we found that both t-BHP and FCCP promoted the cleavage of optic atrophy 1 (OPA1) from the long form into short form during the early stages. In addition, the ATPase family gene 3-like 2, a mitochondrial inner membrane protease, was also markedly increased. Moreover, OPA1 knockdown in myotubes was accompanied by decreased MyHC content, whereas NAC failed to prevent FCCP-induced MyHC decrease with OPA1 knockdown, suggesting that ROS might affect MyHC content by modulating OPA1 cleavage. In addition, hydroxytyrosol acetate (HT-AC), an important compound in virgin olive oil, could significantly prevent t-BHP-induced mitochondrial membrane potential and cell viability loss in myotubes. Specifically, HT-AC inhibited t-BHP-induced OPA1 cleavage and mitochondrial morphology changes, accompanied by improvement on mitochondrial oxygen consumption capacity, ATP productive potential and activities of mitochondrial complex I, II and V. Moreover, both t-BHP- and FCCP-induced MyHC decrease was sufficiently inhibited by HT-AC. Taken together, our data provide evidence indicating that mitochondrial dysfunction-associated OPA1 cleavage may contribute to muscle degeneration, and olive oil compounds could be effective nutrients for preventing the development of muscle disorders.

Anti-proliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: the role of extracellular production of hydrogen peroxide.

PubMed

Fabiani, Roberto; Sepporta, Maria Vittoria; Rosignoli, Patrizia; De Bartolomeo, Angelo; Crescimanno, Marilena; Morozzi, Guido

2012-06-01

Several recently published data suggest that the anti-proliferative and pro-apoptotic properties of hydroxytyrosol [3,4-dihydroxyphenyl ethanol (3,4-DHPEA)] on HL60 cells may be mediated by the accumulation of hydrogen peroxide (H₂O₂) in the culture medium. The aim of this study was to clarify the role played by H₂O₂ in the chemopreventive activities of 3,4-DHPEA on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines and to investigate the effects of cell culture medium components and the possible mechanisms at the basis of the H₂O₂-producing properties of 3,4-DHPEA. The proliferation was measured by the MTT assay and the apoptosis by both fluorescence microscopy and flow cytometry. The concentration of H₂O₂ in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. It was found that the H₂O₂-inducing ability of 3,4-DHPEA is completely prevented by pyruvate and that the exposure of cells to conditions not supporting the H₂O₂ accumulation (addition of either catalase or pyruvate to the culture medium) inhibited the anti-proliferative effect of 3,4-DHPEA. Accordingly, the sensitivity of the different cell lines to the anti-proliferative effect of 3,4-DHPEA was inversely correlated with their ability to remove H₂O₂ from the culture medium. With regard to the mechanism by which 3,4-DHPEA causes the H₂O₂ accumulation, it was found that superoxide dismutase increased the H₂O₂ production while tyrosinase, slightly acidic pH (6,8) and absence of oxygen (O₂) completely prevented this activity. In addition, different transition metal-chelating compounds did not modify the H₂O₂-producing activity of 3,4-DHPEA. The pro-oxidant activity of 3,4-DHPEA deeply influences its 'in vitro' chemopreventive activities. The main initiation step in the H₂O₂-producing activity is the auto-oxidation of 3,4-DHPEA by O₂ with the formation of the semiquinone, superoxide ions (O₂(-)) and 2H(+).

Effect of Extraction Conditions on the Antioxidant Activity of Olive Wood Extracts

PubMed Central

Pérez-Bonilla, Mercedes; Salido, Sofía; Sánchez, Adolfo; van Beek, Teris A.; Altarejos, Joaquín

2013-01-01

An investigation to optimize the extraction yield and the radical scavenging activity from the agricultural by-product olive tree wood (Olea europaea L., cultivar Picual) using six different extraction protocols was carried out. Four olive wood samples from different geographical origin, and harvesting time have been used for comparison purposes. Among the fifty olive wood extracts obtained in this study, the most active ones were those prepared with ethyl acetate, either through direct extraction or by successive liquid-liquid partitioning procedures, the main components being the secoiridoids oleuropein and ligustroside. An acid hydrolysis pretreatment of olive wood samples before extractions did not improve the results. In the course of this study, two compounds were isolated from the ethanolic extracts of olive wood collected during the olives' harvesting season and identified as (7′′R)-7′′-ethoxyoleuropein (1) and (7′′S)-7′′-ethoxyoleuropein (2). PMID:26904608

Rapid fingerprinting and classification of extra virgin olive oil by microjet sampling and extractive electrospray ionization mass spectrometry.

PubMed

Law, Wai Siang; Chen, Huan Wen; Balabin, Roman; Berchtold, Christian; Meier, Lukas; Zenobi, Renato

2010-04-01

Microjet sampling in combination with extractive electrospray ionization (EESI) mass spectrometry (MS) was applied to the rapid characterization and classification of extra virgin olive oil (EVOO) without any sample pretreatment. When modifying the composition of the primary ESI spray solvent, mass spectra of an identical EVOO sample showed differences. This demonstrates the capability of this technique to extract molecules with varying polarities, hence generating rich molecular information of the EVOO. Moreover, with the aid of microjet sampling, compounds of different volatilities (e.g.E-2-hexenal, trans-trans-2,4-heptadienal, tyrosol and caffeic acid) could be sampled simultaneously. EVOO data was also compared with that of other edible oils. Principal Component Analysis (PCA) was performed to discriminate EVOO and EVOO adulterated with edible oils. Microjet sampling EESI-MS was found to be a simple, rapid (less than 2 min analysis time per sample) and powerful method to obtain MS fingerprints of EVOO without requiring any complicated sample pretreatment steps.

Dietary sources of polyphenols in the Mediterranean healthy Eating, Aging and Lifestyle (MEAL) study cohort.

PubMed

Godos, Justyna; Marventano, Stefano; Mistretta, Antonio; Galvano, Fabio; Grosso, Giuseppe

2017-09-01

The aim of this study was to estimate the dietary intake and major food sources of polyphenols in the Mediterranean healthy Eating, Aging and Lifestyles (MEAL) study cohort. A total of 1937 individuals (18 + y) of urban population of Catania, Italy, completed a validated 110-item food frequency questionnaire; Phenol-Explorer database was used to estimate polyphenol intake. Mean intake of polyphenols was 663.7 mg/d; the most abundant classes were phenolic acids (362.7 mg/d) and flavonoids (258.7 mg/d). The main dietary sources of total polyphenols were nuts, followed by tea and coffee as source of flavanols and hydroxycinnamic acids, respectively, fruits (i.e. cherries were sources of anthocyanins and citrus fruits of flavanones) and vegetables (i.e. artichokes and olives were sources of flavones and spinach and beans of flavonols); chocolate, red wine and pasta contributed to flavanols and tyrosols, respectively. These findings will be useful to assess the potential benefits of foods with high polyphenol content.

Low molecular-weight phenols in Tannat wines made by alternative winemaking procedures.

PubMed

Favre, Guzmán; Peña-Neira, Álvaro; Baldi, Cecilia; Hernández, Natalia; Traverso, Sofía; Gil, Graciela; González-Neves, Gustavo

2014-09-01

Low molecular weight phenols of Tannat red wines produced by Traditional Maceration (TM), Prefermentative Cold Maceration (PCM), Maceration Enzyme (ENZ) and grape-Seed Tannins additions (ST), were performed and discussed. Alternatives to TM increased wine phenolic contents but unequally, ST increased mainly smaller flavans-3-ol, PCM anthocyanins and ENZ proanthocyanidins (up to 2250 mg/L). However low molecular weight flavan-3-ols remained below 9 mg/L in all wines, showing that there is not necessarily a correspondence between wine richness in total tannins and flavan-3-ols contents at low molecular weight. PCM wines had particularly high concentrations of tyrosol and tryptophol, yeast metabolism derived compounds. The use of grape-seed enological tannins did not increase grape seed derived phenolic compounds such as gallic acid. Caftaric acid was found in concentrations much higher than those reported in other grape varieties. Wine phenolic content and composition was considerably affected by the winemaking procedures tested. Copyright © 2014 Elsevier Ltd. All rights reserved.

Home Cooking and Phenolics: Effect of Thermal Treatment and Addition of Extra Virgin Olive Oil on the Phenolic Profile of Tomato Sauces.

PubMed

Vallverdú-Queralt, Anna; Regueiro, Jorge; Rinaldi de Alvarenga, José Fernando; Torrado, Xavier; Lamuela-Raventos, Rosa M

2014-04-09

Tomato products are a key component of the Mediterranean diet, which is strongly related to a reduced risk of cardiovascular events. The effect of cooking time (15, 30, 45, and 60 min) and the addition of extra virgin olive oil (5 and 10%) on the phenolic content of tomato sauces was monitored using liquid chromatography coupled to tandem mass spectrometry. Concentration of phenolics in the tomato sauces decreased during the cooking process, with the exception of caffeic acid and tyrosol. The main degradation observed was the oxidation of quercetin, since the hydroxy-function at the C-ring of this flavonoid is not blocked by a sugar moiety, unlike rutin. Higher levels of virgin olive oil in tomato sauce seemed to enhance the extraction of phenolic compounds from the tomato, leading to higher phenolic contents in the sauces. Thus, the food matrix containing the phenolic compounds plays a crucial role in determining their accessibility.

Impact of functional properties and release kinetics on antioxidant activity of biopolymer active films and coatings.

PubMed

Benbettaïeb, Nasreddine; Tanner, Cadhla; Cayot, Philippe; Karbowiak, Thomas; Debeaufort, Frédéric

2018-03-01

This work deals with the study of the release kinetics of some natural antioxidants (ferulic acid, caffeic acid and tyrosol) from chitosan-fish gelatin edible films immersed ethanol at 96%, as well as the kinetics of their antioxidant activity using the DPPH assay. The aim was to determine how film functional properties influence the release kinetic and antioxidant activity. The addition of antioxidants to chitosan-fish gelatin matrix decreased the water vapour permeability by more than 30%. The tensile strength (TS) increased up to 50% after the incorporation of antioxidants. Some molecular interactions between polymer chains and antioxidants were confirmed by FTIR where spectra displayed a shift of the amide-III peak. Films containing caffeic acid or a caffeic-ferulic acid mixture exhibited the highest radical scavenging activity, leading to a 90% antioxidant activity at equilibrium but the release rate controlled the efficacy of the system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phytochemical profiling as a solution to palliate disinfectant limitations.

PubMed

Malheiro, J; Gomes, I; Borges, A; Bastos, M M S M; Maillard, J-Y; Borges, F; Simões, M

2016-10-01

The indiscriminate use of biocides for general disinfection has contributed to the increased incidence of antimicrobial tolerant microorganisms. This study aims to assess the potential of seven phytochemicals (tyrosol, caffeic acid, ferulic acid, cinnamaldehyde, coumaric acid, cinnamic acid and eugenol) in the control of planktonic and sessile cells of Staphylococcus aureus and Escherichia coli. Cinnamaldehyde and eugenol showed antimicrobial properties, minimum inhibitory concentrations of 3-5 and 5-12 mM and minimum bactericidal concentrations of 10-12 and 10-14 mM against S. aureus and E. coli, respectively. Cinnamic acid was able to completely control adhered bacteria with effects comparable to peracetic acid and sodium hypochlorite and it was more effective than hydrogen peroxide (all at 10 mM). This phytochemical caused significant changes in bacterial membrane hydrophilicity. The observed effectiveness of phytochemicals makes them interesting alternatives and/or complementary products to commonly used biocidal products. Cinnamic acid is of particular interest for the control of sessile cells.

The production of aromatic alcohols in non-Saccharomyces wine yeast is modulated by nutrient availability.

PubMed

González, Beatriz; Vázquez, Jennifer; Morcillo-Parra, M Ángeles; Mas, Albert; Torija, María Jesús; Beltran, Gemma

2018-09-01

Aromatic alcohols (tryptophol, phenylethanol, tyrosol) positively contribute to organoleptic characteristics of wines, and are also described as bioactive compounds and quorum sensing molecules. These alcohols are produced by yeast during alcoholic fermentation via the Erhlich pathway, although in non-Saccharomyces this production has been poorly studied. We studied how different wine yeast species modulate the synthesis patterns of aromatic alcohol production depending on glucose, nitrogen and aromatic amino acid availability. Nitrogen limitation strongly promoted the production of aromatic alcohols in all strains, whereas low glucose generally inhibited it. Increased aromatic amino acid concentrations stimulated the production of aromatic alcohols in all of the strains and conditions tested. Thus, there was a clear association between the nutrient conditions and production of aromatic alcohols in most of the wine yeast species analysed. Additionally, the synthesis pattern of these alcohols has been evaluated for the first time in Torulaspora delbrueckii, Metschnikowia pulcherrima and Starmellera bacillaris. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enzymatic hybridization of α-lipoic acid with bioactive compounds in ionic solvents.

PubMed

Papadopoulou, Athena A; Katsoura, Maria H; Chatzikonstantinou, Alexandra; Kyriakou, Eleni; Polydera, Angeliki C; Tzakos, Andreas G; Stamatis, Haralambos

2013-05-01

The lipase-catalyzed molecular hybridization of α-lipoic acid (LA) with bioactive compounds pyridoxine, tyrosol and tyramine was performed in ionic solvents and deep eutectic solvents. The biocatalytic reactions were catalyzed by Candida antarctica lipase B immobilized onto various functionalized multi-walled carbon nanotubes (f-CNTs-CaLB), as well as by commercial Novozym 435. The use of f-CNTs-CaLB leads, in most cases, to higher conversion yields as compared to Novozym 435. The nature and ion composition of ionic solvents affect the performance of the biocatalytic process. The highest conversion yield was observed in (mtoa)NTf2. The high enzyme stability and the relatively low solubility of substrates in specific media account for the improved biocatalytic synthesis of molecular hybrids of LA. Principal component analysis was used to screen for potential lipoxygenase inhibitors. In vitro studies showed that the synthesized compounds exhibit up to 10-fold increased inhibitory activity on lipoxygenase mediated lipid peroxidation as compared to parent molecules. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phenolic profile and fermentation patterns of different commercial gluten-free pasta during in vitro large intestine fermentation.

PubMed

Rocchetti, Gabriele; Lucini, Luigi; Chiodelli, Giulia; Giuberti, Gianluca; Gallo, Antonio; Masoero, Francesco; Trevisan, Marco

2017-07-01

The fate of phenolic compounds, along with short-chain fatty acids (SCFAs) production kinetics, was evaluated on six different commercial gluten-free (GF) pasta samples varying in ingredient compositions, focussing on the in vitro faecal fermentation after the gastrointestinal digestion. A general reduction of both total phenolics and reducing power was observed in all samples, together with a substantial change in phenolic profile over 24h of faecal fermentation, with differences among GF pasta samples. Flavonoids, hydroxycinnamics and lignans degraded over time, with a concurrent increase in low-molecular-weight phenolic acids (hydroxybenzoic acids), alkylphenols, hydroxybenzoketones and tyrosols. Interestingly, discriminant analysis also identified several alkyl derivatives of resorcinol as markers of the changes in phenolic profile during in vitro fermentation. Furthermore, degradation pathways of phenolics by intestinal microbiota have been proposed. Considering the total SCFAs and butyrate production during the in vitro fermentation, different fermentation kinetics were observed among GF pasta post-hydrolysis residues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring the Colonic Metabolism of Grape and Strawberry Anthocyanins and Their in Vitro Apoptotic Effects in HT-29 Colon Cancer Cells.

PubMed

López de Las Hazas, María-Carmen; Mosele, Juana I; Macià, Alba; Ludwig, Iziar A; Motilva, María-José

2017-08-09

Beneficial properties attributed to the intake of fruit and red wine have been associated with the presence of significant amounts of anthocyanins. However, their low absorption and consequent accumulation in the gut have generated the suspicion that colonic metabolites of anthocyanins are probably involved in these protective effects. Grape pomace and strawberry extracts, rich in malvidin- and pelargonidin-glucoside, respectively, were fermented in vitro using human feces as microbial inoculum. After 8 h of anaerobic incubation, the anthocyanins were almost completely degraded, whereas their microbial metabolite concentrations were highest at 24 h. Syringic acid and tyrosol were the main metabolites of grape and strawberry extracts, respectively. On the basis of the metabolites detected, metabolic pathways of malvidin- and pelargonidin-glucosides were proposed. Anthocyanin-rich grape and strawberry extracts and their generated metabolites such as hydroxyphenylacetic acid showed apoptotic effects in HT-29 colon cancer cells and may suggest their possible contribution as anticarcinogenic agents.

Degradation of caffeic acid in subcritical water and online HPLC-DPPH assay of degradation products.

PubMed

Khuwijitjaru, Pramote; Suaylam, Boonyanuch; Adachi, Shuji

2014-02-26

Caffeic acid was subjected to degradation under subcritical water conditions within 160-240 °C and at a constant pressure of 5 MPa in a continuous tubular reactor. Caffeic acid degraded quickly at these temperatures; the main products identified by liquid chromatography-diode array detection/mass spectrometry were hydroxytyrosol, protocatechuic aldehyde, and 4-vinylcatechol. The reaction rates for the degradation of caffeic acid and the formation of products were evaluated. Online high-performance liquid chromatography/2,2-diphenyl-1-picryhydrazyl assay was used to determine the antioxidant activity of each product in the solution. It was found that the overall antioxidant activity of the treated solution did not change during the degradation process. This study showed a potential of formation of antioxidants from natural phenolic compounds under these subcritical water conditions, and this may lead to a discovering of novel antioxidants compounds during the extraction by this technique.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

PubMed

Conde, C; Escribano, B M; Luque, E; Aguilar-Luque, M; Feijóo, M; Ochoa, J J; LaTorre, M; Giraldo, A I; Lillo, R; Agüera, E; Santamaría, A; Túnez, I

2018-05-05

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE). Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated. Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Phosphatidyl derivative of hydroxytyrosol. In vitro intestinal digestion, bioaccessibility, and its effect on antioxidant activity.

PubMed

Martin, Diana; Moran-Valero, Maria I; Casado, Víctor; Reglero, Guillermo; Torres, Carlos F

2014-10-08

Intestinal digestion of phosphatidyl derivatives of HT (PHT) and its bioaccessibility under in vitro conditions was performed. First, an in vitro intestinal digestion model for phospholipids was developed. The impact of digestion in the antioxidant ability of PHT was also assayed. PHT was progressively hydrolyzed to lyso-PHT. However, digestion was slower than the phospholipid control. Nevertheless, most hydrolysis products were found at the micellar phase fraction, meaning a high bioaccessibility. Either PHT or digested PHT showed lower antioxidant activity than HT. However, PHT improved its antioxidant ability after digestion, likely related to lyso-PHT. As a summary, the synthetic phosphatidyl derivative of HT as PHT is recognized by phospholipases during simulation of intestinal digestion, although less efficiently than analogous phospholipids. Nevertheless, taking into account the bioaccessibility and the antioxidant activity of digested PHT, the potential of carriers of HT under the form of phospholipids might be of interest.

Phenols recovery after steam explosion of Olive Mill Solid Waste and its influence on a subsequent biomethanization process.

PubMed

Serrano, Antonio; Fermoso, Fernando G; Alonso-Fariñas, Bernabé; Rodríguez-Gutierrez, Guillermo; Fernandez-Bolaños, Juan; Borja, Rafael

2017-11-01

A promising source of high added value compounds is the Olive Mill Solid Waste (OMSW). The aim of this research was to evaluate the viability of a biorefinery approach to valorize OMSW through the combination of steam explosion, phenols extraction, and anaerobic digestion. Steam explosion treatment increased the total phenol content in the steam exploited OMSW, which was twice than that the total phenol content in raw OMSW, although some undesirable compounds were also formed. Phenol extraction allowed the recovery of 2098mg hydroxytyrosol per kg of OMSW. Anaerobic digestion allowed the partial stabilization of the different substrates, although it was not improved by the steam explosion treatment. The economic suitability of the proposed biorefinery approach is favorable up to a phenol extract price 90.7% lower than the referenced actual price of 520€/kg. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydroxytyrosol prevents reduction in liver activity of Δ-5 and Δ-6 desaturases, oxidative stress, and depletion in long chain polyunsaturated fatty acid content in different tissues of high-fat diet fed mice.

PubMed

Valenzuela, Rodrigo; Echeverria, Francisca; Ortiz, Macarena; Rincón-Cervera, Miguel Ángel; Espinosa, Alejandra; Hernandez-Rodas, María Catalina; Illesca, Paola; Valenzuela, Alfonso; Videla, Luis A

2017-04-11

Eicosapentaenoic acid (EPA, C20:5n-3), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) are long-chain polyunsaturated fatty acids (LCPUFAs) with relevant roles in the organism. EPA and DHA are synthesized from the precursor alpha-linolenic acid (ALA, C18:3n-3), whereas AA is produced from linoleic acid (LA, C18:2n-6) through the action of Δ5 and Δ6-desaturases. High-fat diet (HFD) decreases the activity of both desaturases and LCPUFA accretion in liver and other tissues. Hydroxytyrosol (HT), a natural antioxidant, has an important cytoprotective effects in different cells and tissues. Male mice C57BL/6 J were fed a control diet (CD) (10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks. Animals were daily supplemented with saline (CD) or 5 mg HT (HFD), and blood and the studied tissues were analyzed after the HT intervention. Parameters studied included liver histology (optical microscopy), activity of hepatic desaturases 5 and 6 (gas-liquid chromatography of methyl esters derivatives) and antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase by spectrophotometry), oxidative stress indicators (glutathione, thiobarbituric acid reactants, and the antioxidant capacity of plasma), gene expression assays for sterol regulatory element-binding protein 1c (SREBP-1c) (qPCR and ELISA), and LCPUFA profiles in liver, erythrocyte, brain, heart, and testicle (gas-liquid chromatography). HFD led to insulin resistance and liver steatosis associated with SREBP-1c upregulation, with enhancement in plasma and liver oxidative stress status and diminution in the synthesis and storage of n-6 and n-3 LCPUFAs in the studied tissues, compared to animals given control diet. HT supplementation significantly reduced fat accumulation in liver and plasma as well as tissue metabolic alterations induced by HFD. Furthermore, a normalization of desaturase activities, oxidative stress-related parameters, and tissue n-3 LCPUFA content was observed in HT-treated rats over control animals. HT supplementation prevents metabolic alterations in desaturase activities, oxidative stress status, and n-3 LCPUFA content in the liver and extrahepatic tissues of mice fed HFD.

Phenolic Components and Antioxidant Activity of Wood Extracts from 10 Main Spanish Olive Cultivars.

PubMed

Salido, Sofía; Pérez-Bonilla, Mercedes; Adams, Robert P; Altarejos, Joaquín

2015-07-29

The chemical composition and radical-scavenging activity of wood samples from 10 main Spanish olive cultivars were studied. The wood samples were collected during the pruning works from trees growing under the same agronomical and environmental conditions. The 10 ethyl acetate extracts were submitted to HPLC-DAD/ESI-MS analysis to determine the phenolic constituents. Seventeen compounds were identified (10 secoiridoids, 3 lignans, 2 phenol alcohols, 1 iridoid, and 1 flavonoid) by comparison with authentic samples. Significant quantitative and qualitative differences were found among olive cultivars. The lignan (+)-1-hydroxypinoresinol 1-O-β-d-glucopyranoside was the major compound in all olive cultivars, except in cultivars 'Farga' and 'Picual'. The multivariate analysis of all data revealed three sets of cultivars with similar compositions. Cultivars 'Gordal sevillana' and 'Picual' had the most distinct chemical profiles. With regard to the radical-scavenging activity, cultivar 'Picual', with oleuropein as the major phenolic, showed the highest activity (91.4 versus 18.6-32.7%).

Whole Lyophilized Olives as Sources of Unexpectedly High Amounts of Secoiridoids: The Case of Three Tuscan Cultivars.

PubMed

Cecchi, Lorenzo; Migliorini, Marzia; Cherubini, Chiara; Innocenti, Marzia; Mulinacci, Nadia

2015-02-04

The phenolic profiles of three typical Tuscan olive cultivars, Frantoio, Moraiolo, and Leccino, stored in different conditions (fresh, frozen, and whole lyophilized fruits), have been compared during the ripening period. Our main goals were to evaluate the phenolic content of whole freeze-dried fruits and to test the stability of the corresponding cake in oxidative-stress conditions. The comparison of fresh and whole freeze-dried fruits from the 2012 season gave unexpected results; e.g., oleuropein in lyophilized fruits was up to 20 times higher than in fresh olives with values up to 80.3 g/kg. Over time we noted that the olive pastes obtained from lyophilized olives contained highly stable phenolic compounds, even under strong oxidative stress conditions. Finally, it was also observed that the cake/powder obtained from unripe freeze-dried olives was very poor in oil content and therefore quite suitable for use in nutritional supplements rich in phenolic compounds, such as secoiridoids, which are not widely present in the human diet.

Influence of olive leaf processing on the bioaccessibility of bioactive polyphenols.

PubMed

Ahmad-Qasem, Margarita H; Cánovas, Jaime; Barrajón-Catalán, Enrique; Carreres, José E; Micol, Vicente; García-Pérez, José V

2014-07-02

Olive leaves are rich in bioactive compounds, which are beneficial for humans. The objective of this work was to assess the influence of processing conditions (drying and extraction) of olive leaves on the extract's bioaccessibility. Thus, extracts obtained from dried olive leaves (hot air drying at 70 and 120 °C or freeze-drying) by means of conventional or ultrasound-assisted extraction were subjected to in vitro digestion. Antioxidant capacity, total phenolic content, and HPLC-DAD/MS/MS analysis were carried out during digestion. The dehydration treatment used for the olive leaves did not have a meaningful influence on bioaccessibility. The digestion process significantly (p<0.05) affected the composition of the extracts. Oleuropein and verbascoside were quite resistant to gastric digestion but were largely degraded in the intestinal phase. Nevertheless, luteolin-7-O-glucoside was the most stable polyphenol during the in vitro simulation (43% bioaccessibility). Therefore, this compound may be taken into consideration in further studies that focus on the bioactivity of olive leaf extracts.

Study of the combined effects of ripeness and production area on Bosana oil's quality.

PubMed

Morrone, Lucia; Neri, Luisa; Cantini, Claudio; Alfei, Barbara; Rotondi, Annalisa

2018-04-15

The effects of olive ripeness, areas of production and their interaction on the chemical and sensory characteristics of cv. Bosana oil were assessed. The study was carried out in three areas of the Sassari province, Sardinia (Italy), at three stages of maturation. The results indicated the independence of the two factors: ripeness influenced saturated fatty acids, pigment content and deacetoxy oleuropein aglycone (DAOA) content and didn't affect the sensory characteristics, while production area influenced unsaturated fatty acids, content of vanillic acid and some sensory characters. In order to verify the interdependency of the two factors, statistical analyses (two-way ANOVA) were performed. Our study showed that a thoughtful planning of harvest times and production area could allow to obtain Bosana virgin olive oil of the highest quality. Furthermore, utilizing cultivars that maintain the properties of their oils even at late dates of harvest, it would be possible to optimize harvest times. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phenolic profile and effect of growing area on Pistacia lentiscus seed oil.

PubMed

Mezni, Faten; Slama, Awatef; Ksouri, Riadh; Hamdaoui, Ghaith; Khouja, Mohamed Larbi; Khaldi, Abdelhamid

2018-08-15

In this investigation, we aimed to study, for the first time, the phenolic composition of Pistacia lentiscus seed oils from different growing areas. Extraction of the phenolic fraction from oils was done by methanol/water. Phenolic profiles were determined using chromatographic analysis by High Performance Liquid Chromatography (HPLC-DAD/MSD) and its quantification was done using an internal standard which is unidentified in the studied oil (syringic acid). Forty phenolic compounds were quantified and only eighteen of them were identified. The eight studied oils showed different phenolic profiles. The total phenols amount varied from 538.03 mg/kg oil in Jbel Masour oils to 4260.57 mg/kg oil in oils from Kef Erraai. The highest amount of secoiridoids was reached by Bouchoucha oil containing 366.71 mg/kg oil of Oleuropein aglycon. Oils from Kef Erraai locality contained the highest concentrations in flavonols (377.44 mg/kg oil) and in phenolic acids (2762.67 mg/kg oil). Copyright © 2018 Elsevier Ltd. All rights reserved.

Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo.

PubMed

Elamin, Maha H; Elmahi, Abdelsalam B; Daghestani, Maha H; Al-Olayan, Ebtesam M; Al-Ajmi, Reem A; Alkhuriji, Afrah F; Hamed, Sherifa S; Elkhadragy, Manal F

2017-06-23

Context • Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies Objective • The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved. Design • The research team designed in vivo (animal) and in vitro (cell culture) studies. The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia). Animals • The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1). Intervention • The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (control group)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia. Outcome Measures • The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting. The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappa Β, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used. Conclusions • The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts.

Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil

PubMed Central

Menendez, Javier A.; Joven, Jorge; Aragonès, Gerard; Barrajón-Catalán, Enrique; Beltrán-Debón, Raúl; Borrás-Linares, Isabel; Camps, Jordi; Corominas-Faja, Bruna; Cufí, Sílvia; Fernández-Arroyo, Salvador; Garcia-Heredia, Anabel; Hernández-Aguilera, Anna; Herranz-López, María; Jiménez-Sánchez, Cecilia; López-Bonet, Eugeni; Lozano-Sánchez, Jesús; Luciano-Mateo, Fedra; Martin-Castillo, Begoña; Martin-Paredero, Vicente; Pérez-Sánchez, Almudena; Oliveras-Ferraros, Cristina; Riera-Borrull, Marta; Rodríguez-Gallego, Esther; Quirantes-Piné, Rosa; Rull, Anna; Tomás-Menor, Laura; Vazquez-Martin, Alejandro; Alonso-Villaverde, Carlos; Micol, Vicente; Segura-Carretero, Antonio

2013-01-01

Aging can be viewed as a quasi-programmed phenomenon driven by the overactivation of the nutrient-sensing mTOR gerogene. mTOR-driven aging can be triggered or accelerated by a decline or loss of responsiveness to activation of the energy-sensing protein AMPK, a critical gerosuppressor of mTOR. The occurrence of age-related diseases, therefore, reflects the synergistic interaction between our evolutionary path to sedentarism, which chronically increases a number of mTOR activating gero-promoters (e.g., food, growth factors, cytokines and insulin) and the “defective design” of central metabolic integrators such as mTOR and AMPK. Our laboratories at the Bioactive Food Component Platform in Spain have initiated a systematic approach to molecularly elucidate and clinically explore whether the “xenohormesis hypothesis,” which states that stress-induced synthesis of plant polyphenols and many other phytochemicals provides an environmental chemical signature that upregulates stress-resistance pathways in plant consumers, can be explained in terms of the reactivity of the AMPK/mTOR-axis to so-called xenohormetins. Here, we explore the AMPK/mTOR-xenohormetic nature of complex polyphenols naturally present in extra virgin olive oil (EVOO), a pivotal component of the Mediterranean style diet that has been repeatedly associated with a reduction in age-related morbid conditions and longer life expectancy. Using crude EVOO phenolic extracts highly enriched in the secoiridoids oleuropein aglycon and decarboxymethyl oleuropein aglycon, we show for the first time that (1) the anticancer activity of EVOO secoiridoids is related to the activation of anti-aging/cellular stress-like gene signatures, including endoplasmic reticulum (ER) stress and the unfolded protein response, spermidine and polyamine metabolism, sirtuin-1 (SIRT1) and NRF2 signaling; (2) EVOO secoiridoids activate AMPK and suppress crucial genes involved in the Warburg effect and the self-renewal capacity of “immortal” cancer stem cells; (3) EVOO secoiridoids prevent age-related changes in the cell size, morphological heterogeneity, arrayed cell arrangement and senescence-associated β-galactosidase staining of normal diploid human fibroblasts at the end of their proliferative lifespans. EVOO secoiridoids, which provide an effective defense against plant attack by herbivores and pathogens, are bona fide xenohormetins that are able to activate the gerosuppressor AMPK and trigger numerous resveratrol-like anti-aging transcriptomic signatures. As such, EVOO secoiridoids constitute a new family of plant-produced gerosuppressant agents that molecularly “repair” the aimless (and harmful) AMPK/mTOR-driven quasi-program that leads to aging and aging-related diseases, including cancer. PMID:23370395

Metabolic profile of salidroside in rats using high-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Han, Fei; Li, Yan-ting; Mao, Xin-juan; Zhang, Xiao-shu; Guan, Jiao; Song, Ai-hua; Yin, Ran

2016-03-01

A high-performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FT-ICR MS) method was developed to study the in vivo metabolism of salidroside for the first time. Plasma, urine, bile, and feces samples were collected from male rats after a single intragastric gavage of salidroside at a dose of 50 mg/kg. Besides the parent drug, a total of seven metabolites (three phase I and four phase II metabolites) were detected and tentatively identified by comparing their mass spectrometry profiles with those of salidroside. Results indicated that metabolic pathways of salidroside in male rats included hydroxylation, dehydrogenation, glucuronidation, and sulfate conjugation. Among them, glucuronidation and sulfate conjugation were the major metabolic reactions. And most important, the detection of the sulfation metabolite of p-tyrosol provides a clue for whether the deglycosylation of salidroside occurs in vivo after intragastric gavage. In summary, results obtained in this study may contribute to the better understanding of the safety and mechanism of action of salidroside.

Aromatic Amino Acid-Derived Compounds Induce Morphological Changes and Modulate the Cell Growth of Wine Yeast Species

PubMed Central

González, Beatriz; Vázquez, Jennifer; Cullen, Paul J.; Mas, Albert; Beltran, Gemma; Torija, María-Jesús

2018-01-01

Yeasts secrete a large diversity of compounds during alcoholic fermentation, which affect growth rates and developmental processes, like filamentous growth. Several compounds are produced during aromatic amino acid metabolism, including aromatic alcohols, serotonin, melatonin, and tryptamine. We evaluated the effects of these compounds on growth parameters in 16 different wine yeasts, including non-Saccharomyces wine strains, for which the effects of these compounds have not been well-defined. Serotonin, tryptamine, and tryptophol negatively influenced yeast growth, whereas phenylethanol and tyrosol specifically affected non-Saccharomyces strains. The effects of the aromatic alcohols were observed at concentrations commonly found in wines, suggesting a possible role in microbial interaction during wine fermentation. Additionally, we demonstrated that aromatic alcohols and ethanol are able to affect invasive and pseudohyphal growth in a manner dependent on nutrient availability. Some of these compounds showed strain-specific effects. These findings add to the understanding of the fermentation process and illustrate the diversity of metabolic communication that may occur among related species during metabolic processes. PMID:29696002

Antioxidant capacity index based on gold nanoparticles formation. Application to extra virgin olive oil samples.

PubMed

Della Pelle, Flavio; Vilela, Diana; González, María Cristina; Lo Sterzo, Claudio; Compagnone, Darío; Del Carlo, Michele; Escarpa, Alberto

2015-07-01

A simple gold nanoparticles (AuNPs) based colorimetric assay for the antioxidant activity determination has been developed. The AuNP formation is mediated by extra virgin olive oil (EVOO's) endogenous polyphenols; the reaction is described by a sigmoidal curve. The ratio KAuNPs/Xc(50) (slope of the linear part of the sigmoid/concentration at half value of the absorbance) was found to be the optimal parameter to report the antioxidant capacity with respect to the single KAuNPs or Xc(50) values. The obtained data demonstrated that the compounds with ortho-diphenols functionality are most active in reducing gold (III) to gold (0). Thus, intermediate activity was found for gallic acid, while tyrosol (mono-phenols) had a significant lower activity than the others antioxidant compounds (at least one order of magnitude). In the analysis of olive oil samples, a significant correlation among classical methods used to determine antioxidant activity and the proposed parameter was found with R values in the 0.96-0.97 range. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals

PubMed Central

2017-01-01

Modulation of posttranslational modifications (PTMs), such as protein acetylation, is considered a novel therapeutic strategy to combat the development and progression of cardiovascular diseases. Protein hyperacetylation is associated with the development of numerous cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction. Several phytochemicals exert cardioprotective effects by regulating protein acetylation levels. These effects are mainly exerted via activation of Sirt1 and Sirt3 and inhibition of acetyltransferases. Numerous studies support a cardioprotective role for sirtuin activators (e.g., resveratrol), as well as other emerging modulators of protein acetylation, including curcumin, honokiol, oroxilyn A, quercetin, epigallocatechin-3-gallate, bakuchiol, tyrosol, and berberine. Studies also point to a cardioprotective role for various nonaromatic molecules, such as docosahexaenoic acid, alpha-lipoic acid, sulforaphane, and caffeic acid ethanolamide. Here, we review the vast evidence from the bench to the clinical setting for the potential cardioprotective roles of various phytochemicals in the modulation of sirtuin-mediated deacetylation. PMID:29234485

Towards a high yield recovery of polyphenols from olive mill wastewater on activated carbon coated with milk proteins: Experimental design and antioxidant activity.

PubMed

Yangui, Asma; Abderrabba, Manef

2018-10-01

Activated carbon coated with milk proteins was used for the removal and recovery of phenolic compounds from actual olive mill wastewater (OMW). The extraction of polyphenols using the new adsorbent based on natural coating agent has significant potential compared with traditional extraction methods, as it significantly increases the extraction yield (80%) and overall efficiencies of the process for total phenols (75.4%) and hydroxytyrosol (90.6%) which is the most valuable compound. Complete discussions on the adsorption isotherms, kinetic and thermodynamic were performed and the optimum adsorption variables were investigated using the response surface methodology and the central composite experimental design. The extracted polyphenols exhibited a high antioxidant activity and a fast scavenging effect on DPPH free radical. The strategy devised in this work for polyphenol extraction using modified activated carbon with biological coating agent is of simple design, very effective and ensure the recovery of highly antioxidant extract. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reusing ethyl acetate and aqueous exhausted fractions of dry olive mill residue by saprobe fungi.

PubMed

Aranda, E; García-Romera, I; Ocampo, J A; Carbone, V; Malorni, A; Sannino, F; De Martino, A; Capasso, R

2007-01-01

Some saprobe fungi (Phlebia radiata, Trametes versicolor, Coriolopsis rigida, Pycnoporus cinnabarinus, Fomes sclerodermus or Pleurotus pulmonarius) were able to bioconvert the ethyl acetate fraction (DEAF) and the corresponding aqueous exhausted fraction (EAF) of dry olive mill residue (DOR), reducing their phytotoxicity on Lepidium sativum seeds. Large amount of hydroxytyrosol together with other eight monomeric phenols were found in the native DEAF fraction, which represents a good source of antioxidants. P. radiata, T. versicolor and F. sclerodermus caused an effective phytotoxicity reduction of EAF in the concentration range of 25-3 gl(-1). In particular, in the range between 12.5 and 3 gl(-1), the EAF samples inoculated with P. radiata and F. sclerodermus surprisingly stimulated the germinability of L. sativum, suggesting their use as a potential biofertilizer. This is the first report which showed the bioconversion of the above fractions in shorter time with respect to the previous findings concerning DOR. The possible implications of laccase in the decrease of DEAF and EAF phytotoxicity was also discussed.

Phenolic compounds from the aerial parts of Clematis viticella L. and their in vitro anti-inflammatory activities.

PubMed

Kırmızıbekmez, Hasan; İnan, Yiğit; Reis, Rengin; Sipahi, Hande; Gören, Ahmet C; Yeşilada, Erdem

2018-03-12

Phytochemical investigations on the EtOH extract of Clematis viticella led to the isolation of six flavonoid glycosides, isoorientin (1), isoorientin 3'-O-methyl ether (2), quercetin 7-O-α-L-rhamnopyranoside (3), quercetin 3,7-di-O-α-L-rhamnopyranoside (4), manghaslin (5) and chrysoeriol 7-O-β-D-glucopyranoside (6), one phenylethanol derivative, hydroxytyrosol (7), along with three phenolic acids, caffeic acid (8), (E)-p-coumaric acid (9) and p-hydroxybenzoic acid (10). The structures of the isolates were elucidated on the basis of NMR and HR-MS data. All compounds were isolated from C. viticella for the first time. Compounds 7 and 8 showed significant anti-inflammatory activity at 100 μM by reducing the release of NO in LPS-stimulated macrophages comparable to positive control indomethacin. Compounds 3 and 7 exhibited anti-inflammatory activity through lowering the levels of TNF-α while 1, 3 and 5 decreased the levels of neopterin better than the positive controls.

Drying behaviour, effective diffusivity and energy of activation of olive leaves dried by microwave, vacuum and oven drying methods

NASA Astrophysics Data System (ADS)

Elhussein, Elaf Abdelillah Ali; Şahin, Selin

2018-07-01

Drying is the crucial food processing for bioactive components from plant materials before strating extraction in addition to preservation of raw plant materials during storage period. Olive leaves were dried by various methods such as microwave drying (MD), oven drying (OD) and vacuum drying (VD) at several temperature values in the present study. Mathematical models allow to develop, design and control the processes. 14 emprical equations were used to estimate the drying behaviour and the time required for drying. Convenience of the models were evaluated according to the correlation coefficient ( R 2 ), varience ( S 2 ) and root mean square deviation ( D RMS ). On the other hand, the effective diffusion coefficient and energy for activation were also calculated. Effects of the drying methods on the total phenolic (TPC), flavonoid (TFC) and oleuropein contents and free radical scavenging activity (FRSA) of the olive leaves were also investigated to take into considiration the quality of the dried product. MD has proved to be the fastest drying method having the highest effective diffusivity and the lowest activation energy with a more qualitive product.

Effects of certain polyphenols and extracts on furans and acrylamide formation in model system, and total furans during storage.

PubMed

Oral, Rasim Alper; Dogan, Mahmut; Sarioglu, Kemal

2014-01-01

Using a glucose-glycine and asparagine-fructose system as a Maillard reaction model, the effects of seven polyphenols and solid phase extracts of three plants on the formation of furans and acrylamide were investigated. The polyphenols and extracts were used in biscuit formulation and acrylamide formation was observed. They were used for the storage of the glycine-glucose model system at three different temperatures. The addition of some of the extracts and polyphenols significantly decreased furan formation to different extents. All phenolic compounds and plant extracts decreased in the range of 30.8-85% in the model system except for oleuropein, and all of them decreased in the range of 10.3-19.2% in biscuit. Total furan formation was inhibited by caffeic acid, punicalagin, epicatechin, ECE and PPE during storage. This study evaluated and found the inhibitory effect on the formation of furans and acrylamide in Maillard reactions by the use of some plant extracts and polyphenols. Copyright © 2013 Elsevier Ltd. All rights reserved.

Drying behaviour, effective diffusivity and energy of activation of olive leaves dried by microwave, vacuum and oven drying methods

NASA Astrophysics Data System (ADS)

Elhussein, Elaf Abdelillah Ali; Şahin, Selin

2018-01-01

Drying is the crucial food processing for bioactive components from plant materials before strating extraction in addition to preservation of raw plant materials during storage period. Olive leaves were dried by various methods such as microwave drying (MD), oven drying (OD) and vacuum drying (VD) at several temperature values in the present study. Mathematical models allow to develop, design and control the processes. 14 emprical equations were used to estimate the drying behaviour and the time required for drying. Convenience of the models were evaluated according to the correlation coefficient (R 2 ), varience (S 2 ) and root mean square deviation (D RMS ). On the other hand, the effective diffusion coefficient and energy for activation were also calculated. Effects of the drying methods on the total phenolic (TPC), flavonoid (TFC) and oleuropein contents and free radical scavenging activity (FRSA) of the olive leaves were also investigated to take into considiration the quality of the dried product. MD has proved to be the fastest drying method having the highest effective diffusivity and the lowest activation energy with a more qualitive product.

Phenolic content and antioxidant activity of olive by-products and antioxidant film containing olive leaf extract.

PubMed

Moudache, M; Colon, M; Nerín, C; Zaidi, F

2016-12-01

The antioxidant activity of olive leaf (OL) and cake (OC) extracts with different solvents was evaluated. 70% of aqueous ethanol extract of OL was chosen as the most antioxidant extract based on antiradical activity (DPPH) (95.4±0.3%) and oxygen radical absorbance capacity (ORAC) (0.82±0.07g equivalent Trolox per g of solution) assays. This OL extract was incorporated in two multilayer materials consisting of (i) polyethylene/polyethylene (PE/PE) film and (ii) polyethylene/paper (PE/P). These multilayers were exposed to a gas stream enriched in free radicals to evaluate the scavenging capacity of both materials. PE/PE film exhibited the highest scavenging activity of free radicals (78.8%). Migration of the phenolic compounds from olive by-products into two simulants was performed and demonstrated a non-migrating behavior. The limits of detection and quantification for oleuropein were 0.5μgkg(-1) and 1.7μgkg(-1) and for Luteolin-7-O-glucoside 1.3μgkg(-1) and 4.3μg kg(-1) respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anticorrosion Coating using Olea sp. Leaves Extract

NASA Astrophysics Data System (ADS)

Ikhmal, W. M. K. W. M.; Yasmin, M. Y. N.; Fazira, M. F. M.; Rafizah, W. A. W.; Nik, W. B. Wan; Sabri, M. G. M.

2018-04-01

Olive leaves extract (OLE) was evaluated as green corrosion inhibitor for stainless steel grade 316L (SS316L) in several media using scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization techniques. The Fourier Transform Infrared (FTIR) spectroscopy results reveals several active compound indicated by O-H stretch, C=O stretch, C-OH stretch and C-N stretch which can be attributed to oleuropein and hydroxtyrosol acting as the main inhibiting sources for corrosion. The results obtained also show the inhibition efficiency of OLE increase with the increase of OLE concentration. Through its inhibitive action elucidate from the electrochemical analysis, the extract was found to act as a mixed type inhibitor. Micrographs by SEM showed that the surface of steel which has been coated with 0% and 20% of OLE coating extract possess a lot of pin holes or pores while the steel with 10% of OLE coating extract shows the surface has multiple cracks. This study clearly shows the efficiency of OLE as anticorrosion coating for control of stainless steel in marine application.

Comparative 454 pyrosequencing of transcripts from two olive genotypes during fruit development

PubMed Central

Alagna, Fiammetta; D'Agostino, Nunzio; Torchia, Laura; Servili, Maurizio; Rao, Rosa; Pietrella, Marco; Giuliano, Giovanni; Chiusano, Maria Luisa; Baldoni, Luciana; Perrotta, Gaetano

2009-01-01

Background Despite its primary economic importance, genomic information on olive tree is still lacking. 454 pyrosequencing was used to enrich the very few sequence data currently available for the Olea europaea species and to identify genes involved in expression of fruit quality traits. Results Fruits of Coratina, a widely cultivated variety characterized by a very high phenolic content, and Tendellone, an oleuropein-lacking natural variant, were used as starting material for monitoring the transcriptome. Four different cDNA libraries were sequenced, respectively at the beginning and at the end of drupe development. A total of 261,485 reads were obtained, for an output of about 58 Mb. Raw sequence data were processed using a four step pipeline procedure and data were stored in a relational database with a web interface. Conclusion Massively parallel sequencing of different fruit cDNA collections has provided large scale information about the structure and putative function of gene transcripts accumulated during fruit development. Comparative transcript profiling allowed the identification of differentially expressed genes with potential relevance in regulating the fruit metabolism and phenolic content during ripening. PMID:19709400

Polyphenols Determination in Olive Oil Samples Based on a Thick Film Voltammetric Sensor and a Tyrosinase Biosensor

NASA Astrophysics Data System (ADS)

Capannesi, Cecilia; Palchetti, Ilaria; Mascini, Marco

2000-12-01

The aim of the present work was to compare different techniques to evaluate the variation with the storage time and storage conditions in the phenolic content of an extra-virgin olive oil. A disposable screen-printed sensor (SPE) was coupled with differential pulse voltammetry (DPV) to determine the phenolic fractions after extraction with glycine buffer; DPV parameters were chosen in order to study oxidation peak of oleuropein, that was used as reference compound. Moreover a tyrosinase based biosensor operating in organic solvent (hexane) was assembled, using an amperometric oxygen probe as transducer. Calibration curves were realised in flow injection analysis (F.I.A.) using phenol as substrate. Both of these methods are easy to operate, require no extraction (biosensor) or a rapid extraction procedure (SPE), and the analysis time is short (min.). The results obtained with these two innovative procedures were compared with classical spectrophotometric assay using the Folin-Ciocalteau reagent. Other extra-virgin olive oil quality parameters were investigated with classical methods in order to better define the alteration process and results are reported.

Protective effects of Merlot red wine extract and its major polyphenols in PC12 cells under oxidative stress conditions.

PubMed

Martín, Sara; González-Burgos, Elena; Carretero, M Emilia; Gómez-Serranillos, M Pilar

2013-01-01

The potential effect of the extracts from free-run and pressed Merlot red wine has been evaluated in PC12 cells under oxidative stress situation. Comparing both vinification process, pressed Merlot red wine extract possessed higher neuroprotective activity than the free run wine, possibly attributed to the major content in all global polyphenolic families. High performance liquid chromatography determination of individual polyphenols showed that the major compounds found in Merlot red wine extract were quercetin, catechin, epicatechin, tyrosol, gallic acid, and procyanidins. Pretreatments with these polyphenolic compounds (0.25 mM and 0.1 mM, 24 h) significantly increased cell viability of H(2)O(2) and Fenton reaction treated cells. Moreover, these polyphenols attenuated ROS production and decreased the Redox Index of glutathione (RI = GSSG/GSH + GSSG) in cells treated only with Fenton reaction. Furthermore, some polyphenols induced antioxidant enzymes activity and protein expression. Quercetin was the most active. These results support the beneficial effects of red wine extracts and some of its polyphenols under oxidative stress conditions. This research provides evidences of the preventive properties of wine extracts and its major polyphenols under oxidative stress conditions. © 2012 Institute of Food Technologists®

Isolation of a phytotoxic isocoumarin from Diaporthe eres-infected Hedera helix (English ivy) and synthesis of its phytotoxic analogs.

PubMed

Meepagala, Kumudini M; Briscoe, William E; Techen, Natascha; Johnson, Robert D; Clausen, Brandon M; Duke, Stephen O

2018-01-01

The fungus Diaporthe eres was isolated from a fungal pathogen-infected leaf of Hedera helix (English ivy) exhibiting necrosis. It is hypothesized that the causative fungus produces phytotoxins as evidenced by necrotic lesions on the leaves. The fungus was isolated and grown in Czapek Dox broth culture medium and potato dextrose broth culture medium and identified as Diaporthe eres. The ethyl acetate extracts of the culture broths were phytotoxic to lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). 3,4-Dihydro-8-hydroxy-3,5-dimethylisocoumarin (1) and tyrosol (2) were isolated and identified as the phytotoxic constituents. Six analogs of 3,4-dihydro-isocoumarin were synthesized and shown to be phytotoxic. The synthesized 3,4-dihydro-8-hydroxy-3,7-dimethylisocoumarin and 3,4-dihydro-8-hydroxy-3,3,7-trimethylisocoumarin were two- to three-fold more phytotoxic than the naturally occurring 1 in a Lemna paucicostata growth bioassay. Synthesis and herbicidal activities of the several new analogs of 1 are reported for the first time. These promising molecules should be used as templates for synthesis and testing of more analogs. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Molecular and macromolecular changes in bottle-aged white wines reflect oxidative evolution – Impact of must clarification and bottle closure

NASA Astrophysics Data System (ADS)

Coelho, Christian; Julien, Perrine; Nikolantonaki, Maria; Noret, Laurence; Magne, Mathilde; Ballester, Jordi; Gougeon, Régis D.

2018-04-01

Chardonnay wines from Burgundy, obtained from musts with three levels of clarification (Low, Medium and High) during two consecutive vintages (2009 and 2010) and for two kinds of closures (screw caps and synthetic coextruded closures) were analyzed chemically and sensorially. Three bottles per turbidity level were opened in 2015 in order to assess the intensity of the reductive and/or oxidative aromas (REDOX sensory scores) by a trained sensory panel. The chemical analyses consisted in polyphenols and colloids quantification, followed by a proteomic characterization. For the two vintages, the REDOX sensory scores appeared to be driven both by the type of closure and to a lesser extent by the level of must clarification. Vintages and must racking prefermentative operations were also distinguished by chemical analyses. All white wines from the lowest must turbidity had the lowest REDOX sensory scores. Such wines exhibited lower concentrations in tyrosol and grape reaction product and higher concentrations in colloids with relatively low molecular weights. Among these macromolecules, grape proteins were also quantified, two of them exhibiting concentrations in bottled wines, which were statistically correlated to oxidative evolution in white wines

Molecular and Macromolecular Changes in Bottle-Aged White Wines Reflect Oxidative Evolution–Impact of Must Clarification and Bottle Closure

PubMed Central

Coelho, Christian; Julien, Perrine; Nikolantonaki, Maria; Noret, Laurence; Magne, Mathilde; Ballester, Jordi; Gougeon, Régis D.

2018-01-01

Chardonnay wines from Burgundy, obtained from musts with three levels of clarification (Low, Medium and High) during two consecutive vintages (2009 and 2010) and for two kinds of closures (screw caps and synthetic coextruded closures) were analyzed chemically and sensorially. Three bottles per turbidity level were opened in 2015 in order to assess the intensity of the reductive and/or oxidative aromas (REDOX sensory scores) by a trained sensory panel. The chemical analyses consisted in polyphenols and colloids quantification, followed by a proteomic characterization. For the two vintages, the REDOX sensory scores appeared to be driven both by the type of closure and to a lesser extent by the level of must clarification. Vintages and must racking prefermentative operations were also distinguished by chemical analyses. All white wines from the lowest must turbidity had the lowest REDOX sensory scores. Such wines exhibited lower concentrations in tyrosol and grape reaction product and higher concentrations in colloids with relatively low molecular weights. Among these macromolecules, grape proteins were also quantified, two of them exhibiting concentrations in bottled wines, which were statistically correlated to oxidative evolution in white wines. PMID:29682498

Plant polyphenols as natural drugs for the management of Down syndrome and related disorders.

PubMed

Vacca, Rosa Anna; Valenti, Daniela; Caccamese, Salvatore; Daglia, Maria; Braidy, Nady; Nabavi, Seyed Mohammad

2016-12-01

Polyphenols are secondary metabolites of plants largely found in fruits, vegetables, cereals and beverages, and therefore represent important constituents of the human diet. Increasing studies have demonstrated the potential beneficial effects of polyphenols on human health. Extensive reviews have discussed the protective effects of polyphenols against a series of diseases such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders. Limited studies have investigated the potential therapeutic effects of these natural compounds on neurodevelopmental disorders associated with intellectual disability, such as Down syndrome (DS), for which mitochondrial dysfunctions and oxidative stress are hallmarks and contribute to the deleterious symptoms and cognitive decline. This review, starting from the structure, source, bioavailability and pharmacokinetics of relevant polyphenols, highlights recent studies on the effect and potential molecular mechanism(s) of action of the phenolic compounds epigallocatechin-3-gallate, resveratrol and hydroxytyrosol in restoring mitochondrial energy deficit and in reversing phenotypical alteration in DS. The clinical implications of plant polyphenol dietary supplements as therapeutic tools in managing DS and other intellectual disability-related diseases, is also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of phenolic compounds in virgin olive oil by direct injection in high-performance liquid chromatography with fluorometric detection.

PubMed

Selvaggini, Roberto; Servili, Maurizio; Urbani, Stefania; Esposto, Sonia; Taticchi, Agnese; Montedoro, GianFrancesco

2006-04-19

Hydrophilic phenols are the most abundant natural antioxidants of virgin olive oil (VOO), in which tocopherols and carotenes are also present. The prevalent classes of hydrophilic phenols found in VOO are phenyl alcohols, phenolic acids, secoiridoids such as the dialdehydic form of decarboxymethyl elenolic acid linked to (3,4-dihydroxyphenyl)ethanol or (p-hydroxypheny1)ethanol (3,4-DHPEA-EDA or p-HPEA-EDA) and an isomer of the oleuropein aglycon (3,4-DHPEA-EA), lignans such as (+)-1-acetoxypinoresinol and (+)-pinoresinol, and flavonoids. A new method for the analysis of VOO hydrophilic phenols by direct injection in high-performance liquid chromatography (HPLC) with the use of a fluorescence detector (FLD) has been proposed and compared with the traditional liquid-liquid extraction technique followed by the HPLC analysis utilizing a diode array detector (DAD) and a FLD. Results show that the most important classes of phenolic compounds occurring in VOO can be evaluated using HPLC direct injection. The efficiency of the new method, as compared to the liquid-liquid extraction, was higher to quantify phenyl alcohols, lignans, and 3,4-DHPEA-EA and lower for the evaluation of 3,4-DHPEA-EDA and p-HPEA-EDA.

Quantity and quality of secoiridoids and lignans in extra virgin olive oils: the effect of two- and three-way decanters on Leccino and Raggiola olive cultivars.

PubMed

Antonini, Elena; Farina, Alfonso; Scarpa, Emanuele Salvatore; Frati, Alessandra; Ninfali, Paolino

2016-01-01

In this investigation, 14 extra virgin olive oils (EVOOs), produced with Leccino and Raggiola olive cultivars, by a new two-way (2W) decanter were compared with 14 EVOOs produced by means of a conventional three-way (3W) decanter. The 2W EVOOs had higher phenol concentrations, as shown by high-performance liquid chromatography/diode array detection (HPLC-DAD) analysis and yielded a higher extraction of the 3,4-DHPEA-EDA (oleacein), 3,4-DHPEA-EA (oleuropein aglycone) and p-HPEA-EDA (oleocanthal). The concentrations of lignans, (+)-pinoresinol and (+)-1-acetoxypinoresinol, detected by HPLC-FLD equipment, were higher in the 2W EVOOs than they were in EVOOs produced using the 3W system. Total phenols, detected by the Folin-Ciocalteu assay, were lower than those obtained by HPLC, but they significantly correlated (p < 0.05). The antioxidant capacity (ORAC) values of 2W EVOOs were higher than those of 3W EVOOs. In conclusion, the 2W system provided high-quality phenol EVOOs and became an indispensable tool when adverse climatic conditions reduced the olive secoiridoid concentration.

Evaluation of interactions between RAW264.7 macrophages and small molecules by capillary electrophoresis.

PubMed

Wang, Feng-Qin; Li, Qiao-Qiao; Zhang, Qian; Wang, Yin-Zhen; Hu, Yuan-Jia; Li, Peng; Wan, Jian-Bo; Yang, Feng-Qing; Xia, Zhi-Ning

2017-03-01

In this study, the affinity interactions between RAW 264.7 macrophages and three small molecules including naringin, oleuropein and paeoniflorin were evaluated by affinity capillary electrophoresis (ACE), partial filling affinity capillary electrophoresis (PFACE) and frontal analysis capillary electrophoresis (FACE), respectively. The result indicated that ACE (varying concentrations of cell suspension were filled in the capillary as receptor) may not be suitable for the evaluation of interactions between cell and small molecules due to the high viscosity of cell suspension; PFACE can qualitatively evaluate the interaction, but the difference in viscosity between RAW264.7 suspension and buffer effects on the liner relationship between filling length and injection time, which makes the calculation of binding constant difficult. Furthermore, based on the PFACE results, naringin showed stronger interaction with macrophages than the other two molecules; taking advantage of the aggregation phenomenon of cell induced by electric field, FACE was successfully used to determine the stoichiometry (n = 5×10 9 ) and binding constant (K b = 1×10 4 L/mol) of the interaction between RAW264.7 and naringin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modification of pomological characteristics and flavour components of fruits and virgin olive oil following wastewater irrigation and soil tillage.

PubMed

Tekaya, Meriem; Chehab, Hechmi; Flamini, Guido; Gharbi, Ines; Mahjoub, Zoubeir; Laamari, Salwa; Chihaoui, Badreddine; Boujnah, Dalenda; Hammami, Mohamed; Mechri, Beligh

2018-06-01

The experiment was carried out on olive trees cv. Chemlali, during two successive years (2013/2014). Two irrigation treatments (IT: Trees irrigated with wastewater; TRC: Trees grown under rainfed condition) were combined with two tillage practices (TTS: Trees grown in tilled soil; TNTS: Trees grown in non-tilled soil). The results of the study showed that wastewater irrigation combined with soil tillage improved the pomological characteristics of olive fruits. The tree yield increase was substantial for IT and TTS. However, most of the identified phenolic compounds, especially oleuropein, mainly accumulated in olive fruits of the TC block (TNTS + TRC), suggesting a marked improvement in the nutritional value of these fruits. Moreover, fruits of TNTS had high contents of sugar compounds, required for the synthesis of the fruit storage material. The study also showed that the agronomic practices affected the amounts of some aromatic compounds responsible for the distinctive flavour notes of olive oil. Agronomic practices may affect considerably the commercial and nutritional values and the sensorial quality of the commodities. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Quorum-sensing in yeast and its potential in wine making.

PubMed

Avbelj, Martina; Zupan, Jure; Raspor, Peter

2016-09-01

This mini-review synthesises the present knowledge of microbial quorum-sensing, with a specific focus on quorum-sensing in yeast, and especially in wine yeast. In vine and wine ecosystems, yeast co-interact with a large variety of microorganisms, thereby affecting the fermentation process and, consequently, the flavour of the wine. The precise connections between microbial interactions and quorum-sensing remain unclear, but we describe here how and when some species start to produce quorum-sensing molecules to synchronously adapt their collective behaviour to new conditions. In Saccharomyces cerevisiae, the quorum-sensing molecules were identified as 2-phenylethanol and tryptophol. However, it was recently shown that also a quorum-sensing molecule formerly identified only in Candida albicans, tyrosol, appears to be regulated in S. cerevisiae according to cell density. This review describes the methods for detection and quantification of those quorum-sensing molecules, their underlying mechanisms of action, and their genetic background. It also examines the external stimuli that evoke the quorum-sensing mechanism in the wine-processing environment. The review closes with insight into the biotechnological applications that are already making use of the advantages of quorum-sensing systems and indicates the important questions that still need to be addressed in future research into quorum-sensing.

Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities

PubMed Central

2012-01-01

Background Preparation of tyrosyl lipophilic derivatives was carried out as a response to the food, cosmetic and pharmaceutical industries' increasing demand for new lipophilic antioxidants. Results A large series of tyrosyl esters (TyC2 to TyC18:1) with increasing lipophilicity was synthesized in a good yield using lipase from Candida antarctica (Novozyme 435). Spectroscopic analyses of purified esters showed that the tyrosol was esterified on the primary hydroxyl group. Synthetized compounds were evaluated for either their antimicrobial activity, by both diffusion well and minimal inhibition concentration (MIC) methods, or their antileishmanial activity against Leishmania major and Leishmania infantum parasite species. Among all the tested compounds, our results showed that only TyC8, TyC10 and TyC12 exhibited antibacterial and antileishmanial activities. When MIC and IC50 values were plotted against the acyl chain length of each tyrosyl derivative, TyC10 showed a parabolic shape with a minimum value. This nonlinear dependency with the increase of the chain length indicates that biological activities are probably associated to the surfactant effectiveness of lipophilic derivatives. Conclusion These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries. PMID:22264330

Hydroalcoholic extract of Rhodiola rosea L. (Crassulaceae) and its hydrolysate inhibit melanogenesis in B16F0 cells by regulating the CREB/MITF/tyrosinase pathway.

PubMed

Chiang, Hsiu-Mei; Chien, Yin-Chih; Wu, Chieh-Hsi; Kuo, Yueh-Hsiung; Wu, Wan-Chen; Pan, Yu-Yun; Su, Yu-Han; Wen, Kuo-Ching

2014-03-01

We investigated the effects of an aqueous alcohol extract of Rhodiola rosea (R. rosea) and its hydrolysate on melanin synthesis and the mechanisms mediating the activity. The ratio of tyrosol to salidroside was 2.3 in hydroalcoholic extract, and 51.0 in hydrolysate. We found that R. rosea extract and its hydrolysate inhibited melanin synthesis and tyrosinase activity in mouse melanoma cells (B16F0 cells). R. rosea extract also inhibited gene and protein expression of melanocortin 1 receptor (MC1R) and inhibited c-AMP response element binding protein (CREB) phosphorylation, suppressed the activation of AKT and glycogen synthase kinase-3 beta (GSK3β), and inhibited the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase-related protein 1 (TRP-1). R. rosea hydrolysate inhibited the phosphorylation of CREB, the activation of AKT and GSK3β, and the expression of MITF and tyrosinase. Our results suggest that R. rosea extract is a novel tyrosinase inhibitor and that it exerts its effects by regulating the CREB/MITF/tyrosinase pathway in B16F0. Further in vivo studies are needed to determine the effectiveness of R. rosea extract as a skin whitening agent. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anti-inflammatory effects of polyphenols in arthritis.

PubMed

Oliviero, Francesca; Scanu, Anna; Zamudio-Cuevas, Yessica; Punzi, Leonardo; Spinella, Paolo

2018-03-01

Polyphenols have been extensively investigated with regard to their antioxidant, anti-inflammatory, and immunomodulant properties in many inflammatory chronic conditions. The aim of this review is to summarise how these compounds can modulate the inflammatory pathways which characterise the most prevalent arthropathies including osteoarthritis, rheumatoid arthritis and crystal-induced arthritis. Among polyphenols, epigallocatechin gallate, carnosol, hydroxytyrosol, curcumin, resveratrol, kaempferol and genistein have been the most widely investigated in arthritis. The most important results of the studies outlined in this article show how polyphenolic compounds are able to inhibit the expression and the release of a number of pro-inflammatory mediators and proteolytic enzymes, the activity of different transcriptional factors and the production of reactive oxygen species in vitro. Studies on animal models of rheumatoid arthritis, osteoarthritis and gout show interesting results in terms of reduced tissue damage, restored cartilage homeostasis, and decreased levels of uric acid, respectively. Despite the multiple protective effects of polyphenols, there are no dietary recommendations for patients affected by rheumatic diseases. Future studies, including intervention trials, should be conducted to determine the relevance of polyphenols consumption or supplementation in arthritis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The impact of fruit maturation on bioactive microconstituents, inhibition of serum oxidation and inflammatory markers in stimulated PBMCs and sensory characteristics of Koroneiki virgin olive oils from Messenia, Greece.

PubMed

Kaliora, Andriana C; Artemiou, Anna; Giogios, Ioannis; Kalogeropoulos, Nick

2013-08-01

Olive fruits from the Koroneiki cultivar (Olea europaea L.) grown in Messenia, Greece, were hand-picked from the same trees in progressive maturity stages, covering three months, and processed identically with a commercial olive mill and a three-phase decanter. Data on quality parameters, and antioxidant activity of the obtained oils were collected by employing the conventional analytical methods set by European Union Commission Regulation no. 61/2011. Additionally, the potential of oils' polar extract to inhibit total serum lipid oxidation and inflammatory markers in stimulated human mononuclear cells was assayed. The results showed that ripening caused an increase in monounsaturated and decrease in polyunsaturated fatty acids, as well as an increase in phenolic compounds - mainly hydroxytyrosol - and in squalene. The extracts' ferric reducing power was in line with the increase of phenolic compounds. In later stages of maturation, lipoprotein oxidation was less potent and the decrease of inflammatory markers in stimulated human mononuclear cells was more powerful. Sensory evaluation detected differences in oils' "bitter" attributes, while the analysis of oils' volatiles revealed quantitative differences.

Extraction, Separation, and Identification of Phenolic Compounds in Virgin Olive Oil by HPLC-DAD and HPLC-MS

PubMed Central

Tasioula-Margari, Maria; Tsabolatidou, Eleftheria

2015-01-01

The aim of this study was to evaluate the recovery of individual phenolic compounds extracted from virgin olive oil (VOO), from different Greek olive varieties. Sufficient recoveries (90%) of all individual phenolic compounds were obtained using methanol as an extraction solvent, acetonitrile for residue solubilization, and two washing steps with hexane. Moreover, in order to elucidate structural characteristics of phenolic compounds in VOO, high performance liquid chromatography with a diode array detector (HPLC-DAD) at 280 and 340 nm and HPLC coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) in the negative-ion mode were performed. The most abundant phenolic compounds were oleuropein derivatives with m/z 319 and 377 and ligstroside derivatives with m/z 303, 361. Lignans, such as 1-acetoxypinoresinol and pinoresinol were also present in substantial quantities in the phenolic fraction. However, pinoresinol was co-eluted with dialdehydic form of ligstroside aglycone (DAFLA) and it was not possible to be quantified separately. The phenolic extracts, obtained from different VOO samples, yielded similar HPLC profiles. Differences, however, were observed in the last part of the chromatogram, corresponding to isomers of the aldehydic form of ligstroside aglycone. Oxidized phenolic products, originating from secoiridoids, were also detected. PMID:26783843

Dry olive leaf extract counteracts L-thyroxine-induced genotoxicity in human peripheral blood leukocytes in vitro.

PubMed

Topalović, Dijana Žukovec; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Dekanski, Dragana; Spremo-Potparević, Biljana

2015-01-01

The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger.

Dry Olive Leaf Extract Counteracts L-Thyroxine-Induced Genotoxicity in Human Peripheral Blood Leukocytes In Vitro

PubMed Central

Žukovec Topalović, Dijana; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Spremo-Potparević, Biljana

2015-01-01

The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger. PMID:25789081

White grape pomace as a source of dietary fibre and polyphenols and its effect on physical and nutraceutical characteristics of wheat biscuits.

PubMed

Mildner-Szkudlarz, Sylwia; Bajerska, Joanna; Zawirska-Wojtasiak, Renata; Górecka, Danuta

2013-01-01

Grapes are one of the world's staple fruit crops, with about 80% of the yield being utilised for winemaking. Since grape by-products still contain large amounts of secondary metabolites, uses other than as fertilisers might be appropriate. In this study, white grape pomace (WGP) was incorporated in wheat flour at levels of 10, 20 and 30% (w/w) to investigate its influence on rheological, nutraceutical, physical and sensory properties. Farinograph characteristics of dough with different levels of WGP showed a decrease in water absorption from 56.4% (0% WGP) to 45.9% (30% WGP). Addition of WGP reduced hardness and caused a deterioration in brightness and yellowness of all enriched samples. The smallest addition of WGP (10%) caused an approximately 88% increase in total dietary fibre content as compared with the control. The content of phenolic compounds increased from 0.11 mg g⁻¹ with 0% WGP to 1.07 mg g⁻¹ with 30% WGP. The most stable phenols were as follows: γ-resorcylic acid < gallic acid < tyrosol < catechin < isovanilic acid. An assay of radical-scavenging activity showed that WGP addition greatly enhanced the antioxidant properties of biscuits. Acceptable biscuits were obtained when incorporating 10% WGP. WGP might be utilised for the novel formulation of biscuits as an alternative source of dietary fibre and phenols. Copyright © 2012 Society of Chemical Industry.

An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

PubMed

Fusi, Jonathan; Bianchi, Sara; Daniele, Simona; Pellegrini, Silvia; Martini, Claudia; Galetta, Fabio; Giovannini, Luca; Franzoni, Ferdinando

2018-05-01

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Immunosuppressive phenolic compounds from Hydnora abyssinica A. Braun.

PubMed

Koko, Waleed S; Mesaik, Mohamed A; Ranjitt, Rosa; Galal, Mohamed; Choudhary, Muhammad I

2015-11-09

Hydnora abyssinica (HA) A. Braun is an endemic Sudanese medicinal plant traditionally used as anti-inflammatory and against many infectious diseases. However, it proved to be very rich in phenols and tannins, so the present study was undertaken to investigate the immunomodulatory potential of the whole plant ethanolic extract and its isolated compounds. Lymphocyte proliferation, chemiluminescence and superoxide reduction assays were used for immunomodulatory evaluation. While, MTT (3-(4, 5-dimethylthazol-2-yl)-2, 5-diphenyl tetrazonium bromide) test was performed on 3 T3 cell line clone in order to evaluate the cytoxicity effect of the extracts and isolated compounds of phenolic derivatives which were carried out by chromotographic techniques. Catechin, (1), tyrosol (2) and benzoic acid, 3, 4, dihydroxy-, ethyl ester (3) compounds were isolated from HA ethanolic extract which revealed potent immunosuppressive activity against reactive oxygen species from both polymorph nuclear cells (PMNs) (45-90 % inhibition) and mononuclear cells (MNCs) (30 -65 % inhibition), T lymphocyte proliferation assay (70-93 % inhibition) as well as potent inhibitory effect against superoxide production (42-71 % inhibition) at concentrations of 6.25-100 μg/mL. Catechin (1) was found the most potent immunosuppressive agent among all constituents examined. These results can support the traditional uses of H. abyssinica extracts as anti-inflammatory and immunosuppressive and further investigations of the mode of action and other pharmacological studies are highly desirable.

Effect of daily intake of pomegranate juice on fecal microbiota and feces metabolites from healthy volunteers.

PubMed

Mosele, Juana I; Gosalbes, María-José; Macià, Alba; Rubió, Laura; Vázquez-Castellanos, Jorge F; Jiménez Hernández, Nuria; Moya, Andrés; Latorre, Amparo; Motilva, María-José

2015-10-01

The purpose of the study was to evaluate the effect, regarding the metabolic and microbial profile of feces, of diet supplementation of healthy adults with pomegranate juice (PJ). Twelve healthy adults were recruited to the study, which consisted of the intake of 200 mL/day of PJ during 4 weeks. Feces were collected before and after the supplementation with PJ. Metabolites (phenolic catabolites, short-chain fatty acids, and fecal steroids) and microbial profile were analyzed at baseline and at 4 weeks. Fecal phenolic metabolites, 3-phenylpropionic acid, catechol, hydroxytyrosol, and urolithin A, showed a significant increase in their concentration after supplementation with PJ. Among fecal steroids, parallel to the significant increase of cholesterol concentration, a significant decrease of coprostanol was observed. Although no significant changes in the microbiota profile were observed, different relationships between initial microbiota and the metabolites produced were found. Catechol showed positive and negative correlation with Oscillospora and Paraprevotella genera, respectively, and 3-phenylpropionic acid was positively correlated with Odoribacter genus. Inclusion of PJ in the diet did not significantly alter the gut microbiota composition in healthy adults, but the individual bacterial composition could contribute to the generation of potential health-promoting phenolic metabolites. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cytoprotective effects of phenolic antioxidants and essential fatty acids in human blood monocyte and neuroblastoma cell lines: surrogates for neurological damage in vivo.

PubMed

Young, Julie; Wahle, Klaus W J; Boyle, Susanne P

2008-01-01

Oxidative stress is implicated in the development of a range of neurological diseases. There is increasing interest in the neuroprotective efficacy of antioxidants in modulating such processes with at least one polyphenolic being tested as a prophylactic in Alzheimer's disease. Beneficial effects of adjunctive n-3 polyunsaturated fatty acids with combined intakes of vitamin C and E on both the positive and negative symptoms of schizophrenia have been reported. Robust in vitro systems are desirable, enabling a mechanistic investigation of the molecular mechanisms underpinning such effects and identification of further potentially efficacious nutraceuticals. A comparative study employing a human lymphoblastoid cell line derived from a subject with early onset schizophrenia, a neuroblastoma IMR-32 cell line and the histiocytic lymphoma U937 cell line was undertaken. The cytoprotective effects of two phenols in affording protection to cellular DNA from an oxidative challenge were assessed in untreated and fatty acid treated cell lines. Marked differences in the uptake of fatty acids by the cell types were found and the IMR-32 cell line was most susceptible to the oxidant challenge. Hydroxytyrosol gave significant cytoprotection in all three-cell lines and this possible neuroprotective efficacy warrants further investigation, both in vitro and in vivo.

The recovery of polyphenols from olive mill waste using two adsorbing vegetable matrices.

PubMed

Ena, Alba; Pintucci, Cristina; Carlozzi, Pietro

2012-02-20

Olive mill wastewater (OMW) is considered one of the most pollutive waste materials in the Mediterranean basin. However, its phenolic fraction should be recovered, since it has been shown to have incredible benefits for health. In the present study, the adsorbent and desorbent capacities of Azolla and granular activated carbon (GAC) were investigated. The GAC was found to be more efficient than Azolla in both the adsorption and the desorption of phenols. The total characterization of two powder products obtained from Azolla and GAC desorption is reported, together with their antioxidant and antiradical activities. In the Azolla powder product, total polyphenols were more than twice as numerous as those found in the GAC powder product. The GAC powder contained hydroxytyrosol in concentrations that were 3.5 times higher than those of Azolla. On the other hand, both powder products showed great antiradical activities: the IC₅₀ was found to be 102 mg ml⁻¹ for the Azolla and 199 mg ml⁻¹ for the GAC powders respectively. The oxygen radical absorbance capacity was very high: 4097 μmol TE g⁻¹ Azolla powder product and 1277 μmol TE g⁻¹ of GAC powder products. Copyright © 2011 Elsevier B.V. All rights reserved.

Simultaneous determination of phenylethanoid glycosides and aglycones by capillary zone electrophoresis with running buffer modifier.

PubMed

Dong, Shuqing; Gao, Ruibin; Yang, Yan; Guo, Mei; Ni, Jingman; Zhao, Liang

2014-03-15

Although the separation efficiency of capillary electrophoresis (CE) is much higher than that of other chromatographic methods, it is sometimes difficult to adequately separate the complex ingredients in biological samples. This article describes how one effective and simple way to develop the separation efficiency in CE is to add some modifiers to the running buffer. The suitable running buffer modifier β-cyclodextrin (β-CD) was explored to fast and completely separate four phenylethanoid glycosides and aglycones (homovanillyl alcohol, hydroxytyrosol, 3,4-dimethoxycinnamic acid, and caffeic acid) in Lamiophlomis rotata (Lr) and Cistanche by capillary zone electrophoresis with ultraviolet (UV) detection. It was found that when β-CD was used as running buffer modifier, a baseline separation of the four analytes could be accomplished in less than 20 min and the detection limits were as low as 10(-3) mg L(-1). Other factors affecting the CE separation, such as working potential, pH value and ionic strength of running buffer, separation voltage, and sample injection time, were investigated extensively. Under the optimal conditions, a successful practical application on the determination of Lr and Cistanche samples confirmed the validity and practicability of this method. Copyright © 2014 Elsevier Inc. All rights reserved.

Phenylpropanoids are key players in the antioxidant defense to ozone of European ash, Fraxinus excelsior.

PubMed

Cotrozzi, Lorenzo; Campanella, Alessandra; Pellegrini, Elisa; Lorenzini, Giacomo; Nali, Cristina; Paoletti, Elena

2018-03-01

Physiological and biochemical responses to ozone (O 3 ) (150 ppb, 8 h day -1 , 35 consecutive days) of two Italian provenances (Piedmont and Tuscany) of Fraxinus excelsior L. were evaluated, with special attention to the role of phenylpropanoids. Our results indicate (i) the high O 3 sensitivity especially of Piedmont provenance (in terms of visible injury, water status, and photosynthetic apparatus); (ii) although the intra-specific sensitivity to O 3 between provenances differs (mainly due to different stomatal behaviors since only Tuscany plants partially avoided the uptake of the pollutant gas), both provenances showed detoxification and defense mechanisms; (iii) the crucial participation of phenylpropanoids, with a key role played by flavonoids (especially quercitrin): among this class of metabolites, isoquercitrin is the principal player in the lower O 3 sensitivity of Tuscany plants, together with lignins; (iv) although coumarins (typical compounds of Fraxinus) were severely depressed by O 3 , isofraxidin was triggered suggesting a key role in reactive oxygen species (ROS) detoxification, as well as trans-chalcone. Furthermore, the different behavior of verbascoside and oleuropein among provenances lead us to speculate on their influence in the tentatively repair or acclimation shown by Piedmont plants at the end of the exposure. Finally, the intra-specific O 3 sensitivity may be also due to de novo peaks triggered by O 3 not yet associated to some chemicals.

Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities.

PubMed

Kim, Yeon-Ju; Ji, Seung Taek; Kim, Da Yeon; Jung, Seok Yun; Kang, Songhwa; Park, Ji Hye; Jang, Woong Bi; Yun, Jisoo; Ha, Jongseong; Lee, Dong Hyung; Kwon, Sang-Mo

2018-06-12

Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of CD34+ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against H2O2-induced oxidative stress via the augmented expression of Bcl-2, a prosurvival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

Ethnobotanical survey, chemical composition, and antioxidant capacity of methanolic extract of the root bark of Annona cuneata Oliv.

PubMed

Khallouki, Farid; Haubner, Roswitha; Ulrich, Cornelia M; Owen, Robert W

2011-11-01

The root bark of Annona cuneata Oliv. is traditionally used in the Democratic Republic of Congo to treat several debilitating conditions, such as hernia, female sterility, sexual asthenia, and parasitic infections. However, little is known about the composition of the secondary plant substances, which may contribute to these traditional medicinal effects. We conducted an ethnobotanical study and then evaluated the composition of the secondary plant substances in extracts of the root bark by using spectroscopic methods. After delipidation, the root bark was lixiviated in methanol, and components in the extract were studied by gas chromatography-mass spectometry, high-performance liquid chromatography (HPLC)-electrospray ionization-MS and nano-electrospray ionization-MS-MS. These methods identified 13 secondary plant substances (almost exclusively phenolic compounds): p-hydroxybenzaldehyde (I), vanillin (II), tyrosol (III), 3,4-dihydroxybenzaldehyde (IV), p-hydroxybenzoic acid (V), vanillyl alcohol (VI), syringaldehyde (VII), 4-hydroxy-3-methoxyphenylethanol (VIII), vanillic acid (IX), 3,4-dihydroxybenzoic acid (X), syringic acid (XI), and ferulic acid (XII), along with the phytosterol squalene (XIII). In the HPLC-based hypoxanthine/xanthine oxidase antioxidant assay system, the methanolic extract exhibited potent antioxidant capacity, with a 50% inhibitory concentration of 72 μL, equivalent to 1.38 mg/mL of raw extract. Thus, a methanol extract of A. cuneata Oliv. contained a range of polyphenolic compounds, which may be partly responsible for its known traditional medicinal effects. More detailed studies on the phytochemistry of this important plant species are therefore warranted.

Chemoenzymatic Synthesis and α-Glucosidase Inhibitory Activity of Dimeric Neolignans Inspired by Magnolol.

PubMed

Pulvirenti, Luana; Muccilli, Vera; Cardullo, Nunzio; Spatafora, Carmela; Tringali, Corrado

2017-05-26

A chemoenzymatic synthesis of a small library of dimeric neolignans inspired by magnolol (1) is reported. The 2-iodoxybenzoic acid (IBX)-mediated regioselective ortho-hydroxylation of magnolol is described, affording the bisphenols 6 and 7. Further magnolol analogues (12, 13, 15-17, 19-23) were obtained from eugenol (3), tyrosol (4), and homovanillic alcohol (5), through horseradish peroxidase (HRP)-mediated oxidative coupling and regioselective ortho-hydroxylation or ortho-demethylation in the presence of IBX, followed by reductive treatment with Na 2 S 2 O 4 . A chemoselective protection/deprotection of the alcoholic group of 4 and 5 was carried out by lipase-mediated acetylation/deacetylation. The dimeric neolignans, together with 1 and honokiol (2), were evaluated as inhibitors of yeast α-glucosidase, in view of their possible utilization and optimization as antidiabetic drugs. The synthetic analogues of magnolol showed a strong inhibitory activity with IC 50 values in the range 0.15-4.1 μM, much lower than those of honokiol and the reference compounds quercetin and acarbose. In particular, a very potent inhibitory activity, with an IC 50 of 0.15 μM, was observed for 1,1'-dityrosol-8,8'-diacetate (15), and comparable inhibitory activities were also shown by bisphenols 6 (0.49 μM), 13 (0.50 μM), and 22 (0.86 μM). A kinetic study showed that 15 acts as a competitive inhibitor, with a K i value of 0.86 μM.

Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity.

PubMed

Wong, Chi C; Cheng, Ka-Wing; Xie, Gang; Zhou, Dingying; Zhu, Cai-Hua; Constantinides, Panayiotis P; Rigas, Basil

2012-02-01

Phospho-nonsteroidal anti-inflammatory drugs (phospho-NSAIDs) are novel NSAID derivatives with improved anticancer activity and reduced side effects in preclinical models. Here, we studied the metabolism of phospho-NSAIDs by carboxylesterases and assessed the impact of carboxylesterases on the anticancer activity of phospho-NSAIDs in vitro and in vivo. The expression of human liver carboxylesterase (CES1) and intestinal carboxylesterase (CES2) in human embryonic kidney 293 cells resulted in the rapid intracellular hydrolysis of phospho-NSAIDs. Kinetic analysis revealed that CES1 is more active in the hydrolysis of phospho-sulindac, phospho-ibuprofen, phospho-naproxen, phospho-indomethacin, and phospho-tyrosol-indomethacin that possessed a bulky acyl moiety, whereas the phospho-aspirins are preferentially hydrolyzed by CES2. Carboxylesterase expression leads to a significant attenuation of the in vitro cytotoxicity of phospho-NSAIDs, suggesting that the integrity of the drug is critical for anticancer activity. Benzil and bis-p-nitrophenyl phosphate (BNPP), two carboxylesterase inhibitors, abrogated the effect of carboxylesterases and resensitized carboxylesterase-expressing cells to the potent cytotoxic effects of phospho-NSAIDs. In mice, coadministration of phospho-sulindac and BNPP partially protected the former from esterase-mediated hydrolysis, and this combination more effectively inhibited the growth of AGS human gastric xenografts in nude mice (57%) compared with phospho-sulindac alone (28%) (p = 0.037). Our results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxylesterases improves the efficacy of phospho-NSAIDs in vitro and in vivo.

Carboxylesterases 1 and 2 Hydrolyze Phospho-Nonsteroidal Anti-Inflammatory Drugs: Relevance to Their Pharmacological Activity

PubMed Central

Wong, Chi C.; Cheng, Ka-Wing; Xie, Gang; Zhou, Dingying; Zhu, Cai-Hua; Constantinides, Panayiotis P.

2012-01-01

Phospho-nonsteroidal anti-inflammatory drugs (phospho-NSAIDs) are novel NSAID derivatives with improved anticancer activity and reduced side effects in preclinical models. Here, we studied the metabolism of phospho-NSAIDs by carboxylesterases and assessed the impact of carboxylesterases on the anticancer activity of phospho-NSAIDs in vitro and in vivo. The expression of human liver carboxylesterase (CES1) and intestinal carboxylesterase (CES2) in human embryonic kidney 293 cells resulted in the rapid intracellular hydrolysis of phospho-NSAIDs. Kinetic analysis revealed that CES1 is more active in the hydrolysis of phospho-sulindac, phospho-ibuprofen, phospho-naproxen, phospho-indomethacin, and phospho-tyrosol-indomethacin that possessed a bulky acyl moiety, whereas the phospho-aspirins are preferentially hydrolyzed by CES2. Carboxylesterase expression leads to a significant attenuation of the in vitro cytotoxicity of phospho-NSAIDs, suggesting that the integrity of the drug is critical for anticancer activity. Benzil and bis-p-nitrophenyl phosphate (BNPP), two carboxylesterase inhibitors, abrogated the effect of carboxylesterases and resensitized carboxylesterase-expressing cells to the potent cytotoxic effects of phospho-NSAIDs. In mice, coadministration of phospho-sulindac and BNPP partially protected the former from esterase-mediated hydrolysis, and this combination more effectively inhibited the growth of AGS human gastric xenografts in nude mice (57%) compared with phospho-sulindac alone (28%) (p = 0.037). Our results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxylesterases improves the efficacy of phospho-NSAIDs in vitro and in vivo. PMID:22085648

Hepatoprotective standardized EtOH-water extract from the seeds of Fraxinus rhynchophylla Hance.

PubMed

Guo, Sen; Guo, Tiantian; Cheng, Ni; Liu, Qingchao; Zhang, Yunting; Bai, Lu; Zhang, Li; Cao, Wei; Ho, Chi-Tang; Bai, Naisheng

2017-04-01

Fraxinus rhynchophylla Hance (Oleaceae), its stem barks are known as Cortex fraxini ( qín pí) listed in Chinese Pharmacopoeia. Phytochemical study has indicated that methanol extracts from Qinpi has protective effect on acute liver injury. The present study investigates the hepatoprotective activity of EtOH-water extract from the seeds of F. rhynchophylla Hance against carbon tetrachloride-induced liver injury in mice. The EtOH-water extract significantly alleviated liver damage as indicated by the decreased levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the malondialdehyde (MDA) content, and increased the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px), and reduced the pathological tissue injury induced by CCl 4 . Quantitative analysis of seven major constituents ( 1-7 ) in EtOH-water extract (EWE) was developed by high performance liquid chromatography-diode-array detector (HPLC-DAD). The current research indicates that the EWE from the seeds of F. rhynchophylla Hance decreased liver index, inhibited the increase of serum aminotransferase induced by CCl 4 , and decreased hepatic MDA content, SOD and GSH-Px activities. These results suggested that the pretreatment with EWE protected mice against CCl 4 -induced liver injuries. Based on the results, the EtOH-water extract from the seeds of F. rhynchophylla Hance is efficacious for prevention and treatment of CCl 4 -induced hepatic injury in mice. Secoiridoid and tyrosol glucosides might be the active ingredients responsible for the biological and pharmacological activities of hepatoprotection.

A new process for the management of olive oil mill waste water and recovery of natural antioxidants.

PubMed

Agalias, Apostolis; Magiatis, Prokopios; Skaltsounis, Alexios-Leandros; Mikros, Emmanuel; Tsarbopoulos, Anthony; Gikas, Evagelos; Spanos, Ioannis; Manios, Thrasyvoulos

2007-04-04

The high polyphenol content of the wastewater is the major environmental problem caused by the olive mills. A pilot scale system for the treatment of the olive oil mills wastewater was developed aiming at the recovery of high added value-contained polyphenols and the reduction of the environmental problems. The treatment system consists of three main successive sections: The first one includes successive filtration stages aiming at the gradual reduction of the wastewater suspended solids up to a limit of 25 microm. The second section includes passing of the filtered wastewater through a series of adsorbent resins (XAD16 and XAD7HP) in order to achieve the de-odoring and decolorization of the wastewater and the removal/ recovery of the polyphenol and lactone content. The third section of the procedure includes the thermal evaporation and recovery of the organic solvents mixture, which has been used in the resin regeneration process, and finally the separation of the polyphenols and other organic substance contents using fast centrifuge partition chromatography. The final outcome of the whole procedure is (i) an odorless yellowish wastewater with a 99.99% reduced content in polyphenols and 98% reduced COD, (ii) an extract rich in polyphenols and lactones with high antioxidant activity and high added value, (iii) an extract containing the coloring substances of the olive fruit, and (iv) pure hydroxytyrosol.

Fast determination of virgin olive oil phenolic metabolites in human high-density lipoproteins.

PubMed

Fernández-Ávila, C; Montes, R; Castellote, A I; Chisaguano, A M; Fitó, M; Covas, M I; Muñoz-Aguallo, D; Nyyssönen, K; Zunft, H J; López-Sabater, M C

2015-07-01

In recent years it has been confirmed that the consumption of olive oil prevents the oxidation of biomolecules owing to its monounsaturated fatty acids (MUFA) and phenolic content. The main objective of the study was to develop an ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method for the determination of phenolic compounds in human high-density lipoprotein (HDL) samples. At the same time, the influence of olive oil consumption on the phenolic metabolite levels was evaluated in a European population. The participants were 51 healthy men, aged 20-60. They were randomized to two consecutive intervention periods with the administration of raw olive oil with low and high polyphenolic content. The UHPLC-MS/MS analytical method has been validated for hydroxytyrosol and homovanillic acid in terms of linearity (r(2)  = 0.99 and 1.00), repeatability (5.7 and 6.5%) reproducibility (6.2 and 7%), recovery (98 to 97%), limits of detection (1.7 to 1.8 ppb) and quantification (5.8 and 6.3 ppb).The levels of the studied metabolites increased significantly after high polyphenolic content virgin olive oil ingestion (p <0.05) compared with lowpolyphenolic content olive oil. Virgin olive oil consumption increases the levels of phenolic metabolites in HDL and thus provides human HDL with more efficient antioxidant protection. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of Phytochemically Characterized Extracts From Syringa vulgaris and Isolated Secoiridoids on Mediators of Inflammation in a Human Neutrophil Model.

PubMed

Woźniak, Marta; Michalak, Barbara; Wyszomierska, Joanna; Dudek, Marta K; Kiss, Anna K

2018-01-01

Aim of the study: The aim of the present study was to investigate the effects of phytochemically characterized extracts connected with the traditional use (infusions and ethanolic extracts) of different parts of Syringa vulgaris (common lilac) on the pro-inflammatory functions of neutrophils. Active compounds were isolated from the most promising extract(s) using bioassay-guided fractionation, and their activity and molecular mechanisms of action were determined. Methods: The extracts were characterized using a HPLC-DAD- MS n method. The effects on ROS, MMP-9, TNF-α, IL-8, and MCP-1 production by neutrophils were measured using luminol-dependent chemiluminescence and enzyme-linked immunosorbent assay (ELISA) methods. The effects on p38MAPK, ERK1/2, JNK phosphorylation, and NF- k B p65 translocation were determined using western blots. Results: The major compounds detected in the extracts and infusions belong to structural groups, including caffeic acid derivatives, flavonoids, and iridoids. All extracts and infusions were able to significantly reduce ROS and IL-8 production. Bioassay-guided fractionation led to the isolation of the following secoiridoids: 2″-epiframeroside, oleonuezhenide, oleuropein, ligstroside, neooleuropein, hydroxyframoside, and framoside. Neooleuropein appeared to be the most active compound in the inhibition of cytokine production by attenuating the MAP kinase pathways. Conclusion: The present study demonstrated that common lilac, which is a traditionally used medicinal plant in Europe, is a valuable source of active compounds, especially neooleuropein.

Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil.

PubMed

D'Angelo, S; Manna, C; Migliardi, V; Mazzoni, O; Morrica, P; Capasso, G; Pontoni, G; Galletti, P; Zappia, V

2001-11-01

3,4-Dihydroxyphenylethanol (DOPET) is the major o-diphenol detectable in extra virgin olive oil, either in free or esterified form. Despite its relevant biological effects, mainly related to its antioxidant properties, little data have been reported so far on its toxicity and metabolism. The aim of the present work is to evaluate DOPET toxicity and to investigate its molecular pharmacokinetics by using the (14)C-labeled diphenol. When orally administered to rats, the molecule does not show appreciable toxicity up to 2 g/kg b.wt. To identify and quantify its metabolites, [(14)C]DOPET has been synthesized and intravenously injected in rats. The pharmacokinetic analysis indicates a fast and extensive uptake of the molecule by the organs and tissues investigated, with a preferential renal uptake. Moreover, 90% of the administered radioactivity is excreted in urine collected up to 5 h after injection, and about 5% is detectable in feces and gastrointestinal content. The characterization of the labeled metabolites, extracted from the organs and urine, has been performed by high-pressure liquid chromatography analysis. In all the investigated tissues, DOPET is enzymatically converted in four oxidized and/or methylated derivatives. Moreover, a significant fraction of total radioactivity is associated with the sulfo-conjugated forms, which also represent the major urinary excretion products. On the basis of the reported results, an intracellular metabolic pathway of exogenously administered DOPET, implying the involvement of catechol-O-methyltransferase, alcohol dehydrogenase, aldehyde dehydrogenase, and phenolsulfotransferase, has been proposed.

High Resolution Mass Spectrometric Analysis of Secoiridoids and Metabolites as Biomarkers of Acute Olive Oil Intake-An Approach to Study Interindividual Variability in Humans.

PubMed

Silva, Sandra; Garcia-Aloy, Mar; Figueira, Maria Eduardo; Combet, Emilie; Mullen, William; Bronze, Maria Rosário

2018-01-01

Phenolic compounds are minor components of extra virgin olive oil (EVOO). Secoiridoids are the major components contributing to the phenolic content of EVOO. Information is lacking regarding their potential as biomarkers for EVOO intake. Healthy volunteers (n = 9) ingested 50 mL of EVOO in a single dose containing 322 mg kg -1 total phenolic content (caffeic acid equivalents) and 6 mg 20 g -1 hydroxytyrosol and its derivatives. Plasma is collected before (0 h) and at 0.5, 1, 2, 4, and 6 h after ingestion. Urine samples are collected prior to ingestion (0 h) and at 0-4, 4-8, 8-15, and 15-24 h. Samples are analyzed by UPLC coupled with an Exactive Orbitrap MS. Partial least squares discriminant analysis with orthogonal signal correction is applied to screen for metabolites that allow sample discrimination. Plasma biomarkers and urine biomarkers are selected although individual variability is observed among volunteers. Results are in accordance with in vitro experiments performed (in vitro digestion and hepatic microsomal activity assays). Plasma (elenolic acid + H 2 ; p-HPEA-EA + H 2 + glucuronide) and urinary (3,4-DHPEA-EA, 3,4-DHPEA-EA + H 2 +glucuronide, methyl 3,4-DHPEA-EA + H 2 +glucuronide) secoiridoid compounds are selected as biomarkers to monitor EVOO intake showing good predictive ability according to multivariate analysis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential response in foliar chemistry of three ash species to emerald ash borer adult feeding.

PubMed

Chen, Yigen; Whitehill, Justin G A; Bonello, Pierluigi; Poland, Therese M

2011-01-01

The emerald ash borer (EAB; Agrilus planipennis Fairmaire; Coleoptera: Buprestidae), is an exotic wood-boring beetle that has been threatening North American ash (Fraxinus spp.) resources since its discovery in Michigan and Ontario in 2002. In this study, we investigated the phytochemical responses of the three most common North American ash species (black, green, and white ash) in northeastern USA to EAB adult feeding. Black ash was the least responsive to EAB adult feeding in terms of the induction of volatile compounds, and levels of only two (indole and benzyl cyanide) of the 11 compounds studied increased. In green ash, levels of two [(E)-β-ocimene and indole] of the 11 volatile compounds studied were elevated, while the levels of two green leaf volatiles [hexanal and (E)-2-hexenal] decreased. White ash showed the greatest response with an increase in levels of seven of the 11 compounds studied. Qualitative differences among ash species were detected. Among the phenolic compounds detected, ligustroside was the only one detected in all three species. Oleuropein aglycone and 2 unidentified compounds were found only in black ash; coumaroylquinic acid and feruloylquinic acid were detected only in green ash; and verbascoside hexoside was detected only in white ash. EAB adult feeding did not elicit or decrease concentrations of any selected individual phenolic compounds. However, although levels of total phenolics from black and green ash foliage were not affected by EAB adult feeding, they decreased significantly in white ash. EAB adult feeding elevated chymotrypsin inhibitors in black ash. The possible ecological implications of these findings are discussed.

Assessment of susceptibility of olive cultivars to the Bactrocera oleae (Gmelin, 1790) and Camarosporium dalmaticum (Thüm.) Zachos & Tzav.-Klon. attacks in Calabria (Southern Italy).

PubMed

Iannotta, Nino; Noce, Maria E; Ripa, Vincenzo; Scalercio, Stefano; Vizzarri, Veronica

2007-01-01

Within the framework of research concerning the application of techniques alternative to chemical pesticides for control of parasites, the C.R.A. Experimental Institute for Olive Growing for many years has been performing a large investigation in order to detect sources of genetic resistance in olive germplasm. In the present study we observed the behavior related to the olive fly (Bactrocera oleae) infestation and Camarosporium dalmaticum infection of ten olive cultivars farmed under the same agronomic and climatic conditions in Calabria, Southern Italy. The sampling and the data collecting were carried out in three different ripening times. The drupe amount of oleuropein and cyanidine was detected by laboratory analyses in order to verify a possible correlation between these molecules and the level of infestation/infection of the above-mentioned parasites. The obtained data were submitted to analysis of variance. In relation to the fungal infection the results displayed that cvs Tonda nera dolce showed the lowest susceptibility, while the cv Giarraffa turned out to be the most susceptible. The less susceptible cultivars to the phytophagous were Tonda nera dolce and Bhardi Tirana. Since the less susceptible cultivar to olive fly attacks are the same observed in relation to the susceptibility to olive fruit rot, it is suggested a relation between the olive fly infestation and the fungal infection. It suggests the utility to achieve these results both to transfer directly to the farmers' world and to emphasize ecosystem health and biodiversity conservation.

The activity of healthy olive microbiota during virgin olive oil extraction influences oil chemical composition.

PubMed

Vichi, Stefania; Romero, Agustí; Tous, Joan; Caixach, Josep

2011-05-11

The activity of olive microbiota during the oil extraction process could be a critical point for virgin olive oil quality. With the aim to evaluate the role of microbiological activity during the virgin olive oil extraction process, just before oil extraction freshly collected healthy olive fruits were immersed in contaminated water from an olive mill washing tank. The oils extracted were then compared with control samples from the same batch of hand-picked olives. The presence of lactic and enteric bacteria, fungi and Pseudomonas on the surface of olives was proved to be much higher in washed than in control olives, with increments in cfu/g between 2 and 3 orders of magnitude. The biogenesis of volatile compounds and the extraction of olive polyphenols and pigments were significantly influenced by the microbiological profile of olives even without any previous storage. In most cases the effect of olive microbiota on oil characteristics was greater than the effect exerted by malaxation time and temperature. Oils from microbiologically contaminated olives showed lower amounts of C5 volatiles and higher levels of C6 volatiles from the lipoxygenase pathway and some fermentation products. On the other hand, a decrease of chlorophylls, pheophytins, xanthophylls and the ratio chlorophyll/pheophytin was observed in these oils. Likewise, the microbiological activity during oil extraction led to significantly lower amounts of polyphenols, in particular of oleuropein derivatives. These differences in olive oil chemical composition were reflected in oil sensory characteristics by the decrease of the green and bitter attributes and by the modification of the oil color chromatic ordinates.

Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

PubMed

Corona, Giulia; Vauzour, David; Hercelin, Justine; Williams, Claire M; Spencer, Jeremy P E

2013-11-10

While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex.

Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells

PubMed Central

Corominas-Faja, Bruna; Cuyàs, Elisabet; Lozano-Sánchez, Jesús; Cufí, Sílvia; Verdura, Sara; Fernández-Arroyo, Salvador; Borrás-Linares, Isabel; Martin-Castillo, Begoña; Martin, Ángel G; Lupu, Ruth; Nonell-Canals, Alfons; Micol, Vicente; Joven, Jorge; Segura-Carretero, Antonio; Menendez, Javier A

2018-01-01

Abstract Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target subpopulations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24−/low CSC. DOA could potently block the formation of multicellular tumorspheres generated from single-founder stem-like cells in a panel of genetically diverse BC models. Pretreatment of BC populations with noncytotoxic doses of DOA dramatically reduced subsequent tumor-forming capacity in vivo. Mice orthotopically injected with CSC-enriched BC-cell populations pretreated with DOA remained tumor-free for several months. Phenotype microarray-based screening pointed to a synergistic interaction of DOA with the mTOR inhibitor rapamycin and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine. In silico computational studies indicated that DOA binds and inhibits the ATP-binding kinase domain site of mTOR and the S-adenosyl-l-methionine (SAM) cofactor-binding pocket of DNMTs. FRET-based Z-LYTE™ and AlphaScreen-based in vitro assays confirmed the ability of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM-dependent methylation activity of DNMTs. Our systematic in vitro, in vivo and in silico approaches establish the phenol-conjugated oleoside DOA as a dual mTOR/DNMT inhibitor naturally occurring in EVOO that functionally suppresses CSC-like states responsible for maintaining tumor-initiating cell properties within BC populations. PMID:29452350

Different anti-adipogenic effects of bio-compounds on primary visceral pre-adipocytes and adipocytes

PubMed Central

Colitti, Monica; Stefanon, Bruno

2016-01-01

Several natural compounds exhibit strong capacity for decreasing triglyceride accumulation, enhancing lipolysis and inducing apoptosis. The present study reports the anti-adipogenic effects of Silybum marianum (SL), Citrus aurantium (CA), Taraxacum officinale (TO), resveratrol (RE), Curcuma longa (CU), caffeine (CF), oleuropein (OL) and docosahexaenoic acid (DHA) in reducing differentiation and increasing lipolysis and apoptosis. Analyses were performed on human primary visceral pre-adipocytes after 10 (P10) and 20 (P20) days of treatment during differentiation and on mature adipocytes after 7 days of treatment (A7). The percentage of apoptosis induced by TO extract in P10 and P20 cells was significantly higher than that induced by all other compounds and in CTRL cells. Triglyceride accumulation was significantly lower in cells treated with DHA, CF, RE in comparison to cells treated with OL and in CTRL cells. Treatments with CF, DHA and OL significantly incremented lipolysis in P20 cells in comparison to other compounds and in CTRL cells. On the contrary, the treatment of A7 cells with OL, CA and TO compounds significantly increased cell lipolysis. The addition of CF in differentiating P20 pre-adipocytes significantly increased the expression of genes involved in inhibition of adipogenesis, such as GATA2, GATA3, WNT1, WNT3A, SFRP5, and DLK1. Genes involved in promoting adipogenesis such as CCND1, CEBPB and SREBF1 were significantly down-regulated by the treatment. The screening of bioactive compounds for anti-adipogenic effects showed that in differentiating cells TO extract was the most effective in inducing apoptosis and CF and DHA extracts were more efficient in inhibition of differentiation and in induction of cell lipolysis. PMID:27540349

Inflammasomes, hormesis, and antioxidants in neuroinflammation: Role of NRLP3 in Alzheimer disease.

PubMed

Pennisi, Manuela; Crupi, Rosalia; Di Paola, Rosanna; Ontario, Maria Laura; Bella, Rita; Calabrese, Edward J; Crea, Roberto; Cuzzocrea, Salvatore; Calabrese, Vittorio

2017-07-01

Alzheimer disease (AD) is a progressive neurodegenerative disorder leading to cognitive decline, neuropsychiatric symptoms, disability, caregiver burden, and premature death. It represents the most prevalent cause of dementia, and its incidence rates exponentially increase with increasing age. The number of Americans living with AD is rapidly increasing. An estimated 5.4 million Americans of all ages have AD in 2016. One in nine people aged 65 and older has AD, and by midcentury, someone in the United States will develop the disease every 33 sec. It is now accepted that neuroinflammation is a common feature of neurological disease. Inflammasomes, which are a multiprotein complex part of the innate immune system, induce inflammation in response to various stimuli, such as pathogens and stress. Inflammasomes activate proinflammatory caspases, such as caspase-1, leading to the activation of the proinflammatory cytokines interleukin (IL)-1b, IL-18, and IL-33, which promote neuroinflammation and brain pathologies. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing-3 (NLRP3) inflammasome is the best characterized in neurodegenerative diseases, in particular AD. Recent research suggests that NLRP3 could possibly be used in targeted therapies to alleviate neuroinflammation. Modulation of endogenous cellular defense mechanisms may be an innovative approach to therapeutic intervention in AD and other disorders associated with neuroinflammation and neurodegeneration. Herein, we introduce the hormetic dose-response concept and present possible mechanisms and applications to neuroprotection. We summarize the mechanisms involved in activation of the NLRP3 inflammasome and its role in neuroinflammation. We also address and propose the potential therapeutic utility of the nutritional antioxidants sulforaphane and hydroxytyrosol against particular signs and symptoms of AD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Polyphenol-based nutraceuticals for the control of angiogenesis: Analysis of the critical issues for human use.

PubMed

Morbidelli, Lucia

2016-09-01

Angiogenesis, the formation of new blood-vessel, is crucial in the pathogenesis of several diseases, and thus represents a druggable target for the prevention and treatment of different disorders. It is nowadays well kwon how diet can control cancer development and progression, and how the use of certain diet components can prevent cancer development. Several studies, also from our lab, now indicate that natural plant products including nutraceuticals modulate tumor angiogenesis. In this review, it is reported how phytochemicals, comprising hydroxytyrosol, resveratrol, genistein, curcumin, and the green tea component epigallocatechin-3-gallate among the others, negatively regulate angiogenesis. A single plant-derived compound may affect both endothelial and tumor cells, with the common denominator of anti-inflammatory and radical scavenger activities. Beside these positive features, documented in cellular and animal models, a series of critical issues should be considered from a pharmacological point of view as: what is the best source of bioactive compounds: food and beverages, extracted phytocomplexes, isolated nutraceuticals or synthetic analogues? How is the bioavailability of the compounds of interest in relation to the above source? Is there any biological activity by circulating metabolic derivatives? What is the best formulation, administration route and posology? How safe are in humans? How strong and reliable are the clinical trials designed for their use alone or in combination with conventional chemotherapy? After a dissertation of these critical points, the conclusion can be drawn that novel and effective strategies should be optimized to improve their bioavailability and efficacy, considering their exploitation as chemopreventive and/or curative approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intake of phenol-rich virgin olive oil improves the postprandial prothrombotic profile in hypercholesterolemic patients.

PubMed

Ruano, Juan; López-Miranda, José; de la Torre, Rafael; Delgado-Lista, Javier; Fernández, Javier; Caballero, Javier; Covas, María Isabel; Jiménez, Yolanda; Pérez-Martínez, Pablo; Marín, Carmen; Fuentes, Francisco; Pérez-Jiménez, Francisco

2007-08-01

Oxidative stress associated with postprandial lipemia contributes to endothelial dysfunction, which shifts hemostasis to a more thrombogenic state. We investigated whether a high concentration of phenols in olive oil can partly reverse this phenomenon. Twenty-one hypercholesterolemic volunteers received 2 breakfasts rich in olive oils with different phenolic contents (80 or 400 ppm) according to a randomized, sequential crossover design. Plasma concentrations of lipid fractions, factor VII antigen (FVIIag), activated factor VII (FVIIa), and plasminogen activator inhibitor-1 (PAI-1) activity were measured at baseline and postprandially. Concentrations of FVIIa increased less (P = 0.018) and plasma PAI-1 activity decreased more (P = 0.021) 2 h after the high-phenol meal than after the low-phenol meal. FVIIa concentrations 120 min after intake of the olive oil with a high phenol content correlated positively with fasting plasma triacylglycerols (P = 0.001), area under the curve (AUC) of triacylglycerols (P = 0.001), and AUC of nonesterified fatty acids (P = 0.024) and negatively with hydroxytyrosol plasma concentrations at 60 min (P = 0.039) and fasting HDL-cholesterol concentrations (P = 0.005). PAI-1 positively correlated with homeostasis model assessment of insulin resistance (P = 0.005) and fasting triacylglycerols (P = 0.025) and inversely with adiponectin (P = 0.026). In a multivariate analysis, the AUCs of nonesterified fatty acids (R(2) = 0.467; beta: 0.787; SE: 0.02; P < 0.001) and adiponectin (R(2) = 0.232; beta: -1.594; SE: 0.629; P < 0.05) were the strongest predictors of plasma FVIIa and PAI-1, respectively. A virgin olive oil with a high content of phenolic compounds changes the postprandial hemostatic profile to a less thrombogenic state.

Phenolic Content of Hypodaphnis Zenkeri and Its Antioxidant Effects against Fenton Reactions’ Mediated Oxidative Injuries on Liver Homogenate

PubMed Central

Moukette Moukette, Bruno; Pieme, Constant Anatole; Nya Biapa, Prosper Cabral; Njimou, Jacques Romain; Ama Moor, Vicky Jocelyne; Stoller, Marco; Bravi, Marco; Ngogang, Jeanne Yonkeu

2014-01-01

Under oxidative stress conditions, endogenous antioxidant defenses are unable to completely inactivate the free radicals generated by an excessive production of reactive oxygen species (ROS). This state causes serious cell damage leading to a variety of human diseases. Natural antioxidants can protect cells against oxidative stress. Hypaodaphnis zenkeri (H. zenkiri) is a plant consumed as a spice in the Cameroonian diet, and its bark has been used in traditional medicine for the treatment of several diseases. The present study aims at investigating the antioxidant activity, which includes free radical scavenging and protective properties of an extract from H. Zenkiri against oxidative damage on a liver homogenate. The free radical assays determined the scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), nitrite oxide (NO) and 2,2-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals and the enzymes, whose protection was to be considered in the liver homogenate, including superoxide dismutase, catalase, and peroxidase. The antioxidative activities were studied using the ferric reducing antioxidant power (FRAP), reductive activity, and phosphomolybdenum antioxidant power (PAP) methods. In addition, the phenolic contents of the extracts were examined. The results showed that these extracts demonstrated significant scavenging properties and antioxidant activities, with the hydro-ethanolic extract of the bark of H. zenkeri (EEH) being the most potent. This extract had the highest total polyphenol (21.77 ± 0.05 mg caffeic acid (CAE)/g dried extract (DE)) and flavonoids (3.34 ± 0.13 mg quercetin (QE)/g dried extract) content. The same extract had significantly greater protective effects on enzyme activities compared to other extracts. The high performance liquied chromatography (HPLC) profile showed higher levels of caffeic acid, OH-tyrosol acid, and rutin in the leaves compared to the bark of H. zenkeri. In conclusion, the ethanolic and hydro-ethanolic extracts of the bark and leaves from H. zenkeri showed an antioxidant and protective potential against oxidative damage. PMID:26785245

White wine induced cardioprotection against ischemia-reperfusion injury is mediated by life extending Akt/FOXO3a/NFkappaB survival pathway.

PubMed

Thirunavukkarasu, Mahesh; Penumathsa, Suresh Varma; Samuel, Samson Mathews; Akita, Yuzo; Zhan, Lijun; Bertelli, Alberto A E; Maulik, Gautam; Maulik, Nilanjana

2008-08-13

Recent studies on the protection afforded by moderate wine consumption against cardiovascular diseases have focused mainly on the activity of red wine in view of its high content of antioxidants, especially polyphenols. White wine lacks polyphenols, but it contains other compounds such as hydroxycinnamic acids (caffeic acid) and monophenols (tyrosol), which are known to have antioxidant properties. Therefore, this study was designed to examine the effect of white wine in myocardial ischemic-reperfusion injury. The experimental rats were gavaged with white wine (Soave Suavia "Le Rive" 2004) at a dosage of 6.5 mL/(kg.rat.day) for 30 days. Rats were divided into four groups: control sham (CS), wine-treated sham (WS), control ischemia (I)/reperfusion (R) (CIR), and wine + IR (WIR). All the rats in both IR groups underwent 30 min occlusion of the left anterior descending coronary artery followed by 8, 24 h, and 30 days of reperfusion (R). Significant reduction in infarct size (21 vs 39%, n = 6), cardiomyocyte (274 vs 384 counts/100 HPF, n = 6), and endothelial cell apoptosis (387 vs 587 counts/100 HPF) was observed in WIR as compared with CIR after 24 h of reperfusion. Echocardiography demonstrated significant increased fractional shortening (32 vs 22%) and ejection fraction (60 vs 44%) following 30 days of reperfusion in WIR rats compared to CIR ( n = 6). In addition, increased phosphorylation of AKT, Foxo3a, and eNOS were found in WS and WIR, as compared to their respective controls. The gel-shift analysis demonstrated significant upregulation of DNA binding activity of NF-kappaB in the white wine-treated groups. This report demonstrated for the first time that the white wine mediated cardioprotection in ischemic reperfused myocardium is through the PI-3kinase/Akt/FOXO3a/e-NOS/NF-kappaB survival pathway.

The importance of chorismate mutase in the biocontrol potential of Trichoderma parareesei

PubMed Central

Pérez, Esclaudys; Rubio, M. Belén; Cardoza, Rosa E.; Gutiérrez, Santiago; Bettiol, Wagner; Monte, Enrique; Hermosa, Rosa

2015-01-01

Species of Trichoderma exert direct biocontrol activity against soil-borne plant pathogens due to their ability to compete for nutrients and to inhibit or kill their targets through the production of antibiotics and/or hydrolytic enzymes. In addition to these abilities, Trichoderma spp. have beneficial effects for plants, including the stimulation of defenses and the promotion of growth. Here we study the role in biocontrol of the T. parareesei Tparo7 gene, encoding a chorismate mutase (CM), a shikimate pathway branch point leading to the production of aromatic amino acids, which are not only essential components of protein synthesis but also the precursors of a wide range of secondary metabolites. We isolated T. parareesei transformants with the Tparo7 gene silenced. Compared with the wild-type, decreased levels of Tparo7 expression in the silenced transformants were accompanied by reduced CM activity, lower growth rates on different culture media, and reduced mycoparasitic behavior against the phytopathogenic fungi Rhizoctonia solani, Fusarium oxysporum and Botrytis cinerea in dual cultures. By contrast, higher amounts of the aromatic metabolites tyrosol, 2-phenylethanol and salicylic acid were detected in supernatants from the silenced transformants, which were able to inhibit the growth of F. oxysporum and B. cinerea. In in vitro plant assays, Tparo7-silenced transformants also showed a reduced capacity to colonize tomato roots. The effect of Tparo7-silencing on tomato plant responses was examined in greenhouse assays. The growth of plants colonized by the silenced transformants was reduced and the plants exhibited an increased susceptibility to B. cinerea in comparison with the responses observed for control plants. In addition, the plants turned yellowish and were defective in jasmonic acid- and ethylene-regulated signaling pathways which was seen by expression analysis of lipoxygenase 1 (LOX1), ethylene-insensitive protein 2 (EIN2) and pathogenesis-related protein 1 (PR-1) genes. PMID:26579090

Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones.

PubMed

Panossian, Alexander; Wikman, Georg; Kaur, Punit; Asea, Alexzander

2009-06-01

Adaptogens are medicinal plants that augment resistance to stress, and increase concentration, performance and endurance during fatigue. Experiments were carried out with BALB/c mice taking ADAPT-232 forte, a fixed combination of three genuine (native) extracts of Eleutherococcus senticocus, Schisandra chinensis and Rhodiola rosea, characterised for the content of active markers eleutherosides, schisandrins, salidroside, tyrosol and rosavin and in doses of about 30, 90 and 180 mg/kg for seven consecutive days followed by forced swimming test to exhaustion. ADAPT-232 forte strongly augments endurance of mice, increasing the time taken to exhaustion (TTE) in a dose-dependent manner from 3.0+/-0.5 to 21.1+/-1.7 min, approximately seven fold. Serum Hsp72 was measured by EIA both in normal and stressful conditions before and after swimming test. Repeated administration of adaptogen dose dependently increases basal level of Hsp72 in serum of mice from 0.8-1.5 to 5.5-6.3 pg/ml. This effect is even stronger than the effect of stress, including both physical (swimming) and emotional impacts: 3.2+/-1.2 pg/ml. Cumulative effect of stress and adaptogen was clearly observed in groups of animals treated with adaptogen after swimming to exhaustion, when serum Hsp72 increased to 15.1+/-1 pg/ml and remained at almost the same level during the 7 days. It can be concluded that adaptogens induce increase of serum Hsp72, regarded as a defense response to stress, and increase tolerance to stress (in our model combination of physical and emotional stresses). It can be suggested that increased tolerance to stress induced by adaptogen is associated with its stimulation of expression of Hsp70 and particularly with Hsp72 production and release into systemic circulation, which is known as a mediator of stress response involved in reparation of proteins during physical load. Our studies suggest that this could be one of the mechanisms of action of plant adaptogens.

Efficacy and safety of a combination of red yeast rice and olive extract in hypercholesterolemic patients with and without statin-associated myalgia.

PubMed

Tshongo Muhindo, Christian; Ahn, Sylvie A; Rousseau, Michel F; Dierckxsens, Yvan; Hermans, Michel P

2017-12-01

Cholesfytol ® , a lipid-lowering dietary supplement with antioxidant and anti-atherosclerotic properties, combines red yeast rice (RYR) and olive extract (5mg hydroxytyrosol equivalent) and represents an alternative for patients who do not wish or are unable to use chemical statins, including individuals with previous statin-associated muscle symptoms (SAMS). A 2-months observational non-randomized study was performed to evaluate the efficacy, tolerance and safety of Cholesfytol ® (1 tablet/day) in 642 hypercholesterolemic patients (mean age: 59 yrs; total cholesterol (TC) ≥200; LDL-C ≥140mg/dl). Patients were followed by 126 GPs, and included irrespective of SAMS history and/or diabetes. None of the patients were taking statins or other lipid-modifying therapy at inclusion. At baseline, 26% had fasting glucose >100 ≤125mg/dL, and 5% >125mg/dL; 32% (n=194) had a SAMS history; and 21% had atherogenic dyslipidemia (AD). In the entire cohort, pre-treatment TC; non-HDL-C; LDL-C; and TG were 259; 200; 168; 158mg/dL, respectively, and decreased significantly on treatment (-17.5% (TC) and -23.3% (LDL-C)). Fasting glucose and HbA 1c decreased between visits. The reduction in lipids was greater in patients with higher values at baseline. For comparable pre-treatment values, patients with SAMS history had reductions in TC, LDL-C, non-HDL-C, and apoB 100 slightly less than patients without myalgia. AD patients had greater on-treatment decrease in TG. Overall, 13 patients reported minor side-effects, and 4 patients reporting myalgia had antecedent SAMS. In conclusion, a substantial decrease in LDL-C was obtained with a combination of RYR and olive extract in high-risk hypercholesterolemic patients, without inducing new-onset SAMS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of virgin olive oil and thyme phenolic compounds on blood lipid profile: implications of human gut microbiota.

PubMed

Martín-Peláez, Sandra; Mosele, Juana Ines; Pizarro, Neus; Farràs, Marta; de la Torre, Rafael; Subirana, Isaac; Pérez-Cano, Francisco José; Castañer, Olga; Solà, Rosa; Fernandez-Castillejo, Sara; Heredia, Saray; Farré, Magí; Motilva, María José; Fitó, Montserrat

2017-02-01

To investigate the effect of virgin olive oil phenolic compounds (PC) alone or in combination with thyme PC on blood lipid profile from hypercholesterolemic humans, and whether the changes generated are related with changes in gut microbiota populations and activities. A randomized, controlled, double-blind, crossover human trial (n = 12) was carried out. Participants ingested 25 mL/day for 3 weeks, preceded by 2-week washout periods, three raw virgin olive oils differing in the concentration and origin of PC: (1) a virgin olive oil (OO) naturally containing 80 mg PC/kg, (VOO), (2) a PC-enriched virgin olive oil containing 500 mg PC/kg, from OO (FVOO), and (3) a PC-enriched virgin olive oil containing a mixture of 500 mg PC/kg from OO and thyme, 1:1 (FVOOT). Blood lipid values and faecal quantitative changes in microbial populations, short chain fatty acids, cholesterol microbial metabolites, bile acids, and phenolic metabolites were analysed. FVOOT decreased seric ox-LDL concentrations compared with pre-FVOOT, and increased numbers of bifidobacteria and the levels of the phenolic metabolite protocatechuic acid compared to VOO (P < 0.05). FVOO did not lead to changes in blood lipid profile nor quantitative changes in the microbial populations analysed, but increased the coprostanone compared to FVOOT (P < 0.05), and the levels of the faecal hydroxytyrosol and dihydroxyphenylacetic acids, compared with pre-intervention values and to VOO, respectively (P < 0.05). The ingestion of a PC-enriched virgin olive oil, containing a mixture of olive oil and thyme PC for 3 weeks, decreases blood ox-LDL in hypercholesterolemic humans. This cardio-protective effect could be mediated by the increases in populations of bifidobacteria together with increases in PC microbial metabolites with antioxidant activities.

Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N.

PubMed

Badreddine, Asmaa; Zarrouk, Amira; Karym, El Mostafa; Debbabi, Meryam; Nury, Thomas; Meddeb, Wiem; Sghaier, Randa; Bezine, Maryem; Vejux, Anne; Martine, Lucy; Grégoire, Stéphane; Bretillon, Lionel; Prost-Camus, Emmanuelle; Durand, Philippe; Prost, Michel; Moreau, Thibault; Cherkaoui-Malki, Mustapha; Nasser, Boubker; Lizard, Gérard

2017-10-23

Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25-50 µM; 24 h) without and with argan oil (0.1% v / v ) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.

Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N

PubMed Central

Badreddine, Asmaa; Zarrouk, Amira; Karym, El Mostafa; Debbabi, Meryam; Nury, Thomas; Meddeb, Wiem; Sghaier, Randa; Bezine, Maryem; Martine, Lucy; Grégoire, Stéphane; Bretillon, Lionel; Durand, Philippe; Prost, Michel; Moreau, Thibault; Cherkaoui-Malki, Mustapha; Nasser, Boubker

2017-01-01

Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25–50 µM; 24 h) without and with argan oil (0.1% v/v) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier. PMID:29065513

Herbal bioactivation: the good, the bad and the ugly.

PubMed

Zhou, Shufeng; Koh, Hwee-Ling; Gao, Yihuai; Gong, Zhi-yuan; Lee, Edmund Jon Deoon

2004-01-09

It has been well established that the formation of reactive metabolites of drugs is associated with drug toxicity. Similarly, there are accumulating data suggesting the role of the formation of reactive metabolites/intermediates through bioactivation in herbal toxicity and carcinogenicity. It has been hypothesized that the resultant reactive metabolites following herbal bioactivation covalently bind to cellular proteins and DNA, leading to toxicity via multiple mechanisms such as direct cytotoxicity, oncogene activation, and hypersensitivity reactions. This is exemplified by aristolochic acids present in Aristolochia spp, undergoing reduction of the nitro group by hepatic cytochrome P450 (CYP1A1/2) or peroxidases in extrahepatic tissues to reactive cyclic nitrenium ion. The latter was capable of reacting with DNA and proteins, resulting in activation of H-ras oncogene, gene mutation and finally carcinogenesis. Other examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming diets. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, and the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase. On the other hand, some herbal/dietary constituents were shown to form reactive intermediates capable of irreversibly inhibiting various CYPs. The resultant metabolites lead to CYP inactivation by chemical modification of the heme, the apoprotein, or both as a result of covalent binding of modified heme to the apoprotein. Some examples include bergamottin, a furanocoumarin of grapefruit juice; capsaicin from chili peppers; glabridin, an isoflavan from licorice root; isothiocyanates found in all cruciferous vegetables; oleuropein rich in olive oil; dially sulfone found in garlic; and resveratrol, a constituent of red wine. CYPs have been known to metabolize more than 95% therapeutic drugs and activate a number of procarcinogens as well. Therefore, mechanism-based inhibition of CYPs may provide an explanation for some reported herb-drug interactions and chemopreventive activity of herbs. Due to the wide use and easy availability of herbal medicines, there is increasing concern about herbal toxicity. The safety and quality of herbal medicine should be ensured through greater research, pharmacovigilance, greater regulatory control and better communication between patients and health professionals.

An integrated process for the recovery of high added-value compounds from olive oil using solid support free liquid-liquid extraction and chromatography techniques.

PubMed

Angelis, Apostolis; Hamzaoui, Mahmoud; Aligiannis, Nektarios; Nikou, Theodora; Michailidis, Dimitris; Gerolimatos, Panagiotis; Termentzi, Aikaterini; Hubert, Jane; Halabalaki, Maria; Renault, Jean-Hugues; Skaltsounis, Alexios-Léandros

2017-03-31

An integrated extraction and purification process for the direct recovery of high added value compounds from extra virgin olive oil (EVOO) is proposed by using solid support free liquid-liquid extraction and chromatography techniques. Two different extraction methods were developed on a laboratory-scale Centrifugal Partition Extractor (CPE): a sequential strategy consisting of several "extraction-recovery" cycles and a continuous strategy based on stationary phase co-current elution. In both cases, EVOO was used as mobile phase diluted in food grade n-hexane (feed mobile phase) and the required biphasic system was obtained by adding ethanol and water as polar solvents. For the sequential process, 17.5L of feed EVOO containing organic phase (i.e. 7L of EVOO treated) were extracted yielding 9.5g of total phenolic fraction corresponding to a productivity of 5.8g/h/L of CPE column. Regarding the second approach, the co-current process, 2L of the feed oil phase (containing to 0.8L of EVOO) were treated at 100mL/min yielding 1.03g of total phenolic fraction corresponding to a productivity of 8.9g/h/L of CPE column. The total phenolic fraction was then fractionated by using stepwise gradient elution Centrifugal Partition Chromatography (CPC). The biphasic solvent systems were composed of n-hexane, ethyl acetate, ethanol and water in different proportions (X/Y/2/3, v/v). In a single run of 4h on a column with a capacity of 1L, 910mg of oleocanthal, 882mg of oleacein, 104mg of hydroxytyrosol were successfully recovered from 5g of phenolic extract with purities of 85%, 92% and 90%, respectively. CPC fractions were then submitted to orthogonal chromatographic steps (adsorption on silica gel or size exclusion chromatography) leading to the isolation of additional eleven compounds belonging to triterpens, phenolic compounds and secoiridoids. Among them, elenolic acid ethylester was found to be new compound. Thin Layer Chromatography (TLC), Nuclear magnetic Resonance (NMR) and High Performance Liquid Chromatography - Diode Array Detector (HPLC-DAD) were used for monitoring and evaluation purposes throughout the entire procedure. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel Phenolic Inhibitors of Small/Intermediate-Conductance Ca2+-Activated K+ Channels, KCa3.1 and KCa2.3

PubMed Central

Oliván-Viguera, Aida; Valero, Marta Sofía; Murillo, María Divina; Wulff, Heike; García-Otín, Ángel-Luis; Arbonés-Mainar, José-Miguel; Köhler, Ralf

2013-01-01

Background KCa3.1 channels are calcium/calmodulin-regulated voltage-independent K+ channels that produce membrane hyperpolarization and shape Ca2+-signaling and thereby physiological functions in epithelia, blood vessels, and white and red blood cells. Up-regulation of KCa3.1 is evident in fibrotic and inflamed tissues and some tumors rendering the channel a potential drug target. In the present study, we searched for novel potent small molecule inhibitors of KCa3.1 by testing a series of 20 selected natural and synthetic (poly)phenols, synthetic benzoic acids, and non-steroidal anti-inflammatory drugs (NSAIDs), with known cytoprotective, anti-inflammatory, and/or cytostatic activities. Methodology/Principal Findings In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM) and resveratrol (EC50 10 µM) as KCa3.1 inhibitors with moderate potency. The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM), followed by mesalamine (EC50≥10 µM). The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyl)oxymethyl]phenyl]methyl 3-fluoro-4-hydroxy-benzoate), was identified as a potent mixed KCa2/3 channel inhibitor with an EC50 of 19 nM for KCa3.1 and 360 pM for KCa2.3, which affected KCa1.1 and Kv channels only at micromolar concentrations. The KCa3.1/KCa2-activator SKA-31 antagonized the 13b-blockade. In proliferation assays, 13b was not cytotoxic and reduced proliferation of 3T3 fibroblasts as well as caffeic acid. In isometric vessel myography, 13b increased contractions of porcine coronary arteries to serotonin and antagonized endothelium-derived hyperpolarization-mediated vasorelaxation to pharmacological KCa3.1/KCa2.3 activation. Conclusions/Significance We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel KCa3.1 inhibitors. The high potency of 13b with pan-activity on KCa3.1/KCa2 channels makes 13b a new pharmacological tool to manipulate inflammation and cancer growth through KCa3.1/KCa2 blockade and a promising template for new drug design. PMID:23516517

Further investigation into maple syrup yields 3 new lignans, a new phenylpropanoid, and 26 other phytochemicals.

PubMed

Li, Liya; Seeram, Navindra P

2011-07-27

Maple syrup is made by boiling the sap collected from certain maple ( Acer ) species. During this process, phytochemicals naturally present in tree sap are concentrated in maple syrup. Twenty-three phytochemicals from a butanol extract of Canadian maple syrup (MS-BuOH) had previously been reported; this paper reports the isolation and identification of 30 additional compounds (1-30) from its ethyl acetate extract (MS-EtOAc) not previously reported from MS-BuOH. Of these, 4 compounds are new (1-3, 18) and 20 compounds (4-7, 10-12, 14-17, 19, 20, 22-24, 26, and 28-30) are being reported from maple syrup for the first time. The new compounds include 3 lignans and 1 phenylpropanoid: 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-(hydroxymethyl)dihydrofuran-2-one (1), (erythro,erythro)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (2), (erythro,threo)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (3), and 2,3-dihydroxy-1-(3,4- dihydroxyphenyl)-1-propanone (18), respectively. In addition, 25 other phenolic compounds were isolated including (threo,erythro)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (4), (threo,threo)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (5), threo-guaiacylglycerol-β-O-4'-dihydroconiferyl alcohol (6), erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol (7), 2-[4-[2,3-dihydro-3-(hydroxymethyl)-5-(3-hydroxypropyl)-7-methoxy-2-benzofuranyl]-2,6-dimethoxyphenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (8), acernikol (9), leptolepisol D (10), buddlenol E (11), (1S,2R)-2-[2,6-dimethoxy-4-[(1S,3aR,4S,6aR)-tetrahydro-4-(4-hydroxy-3,5-dimethoxyphenyl)-1H,3H-furo[3,4-c]furan-1-yl]phenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (12), syringaresinol (13), isolariciresinol (14), icariside E4 (15), sakuraresinol (16), 1,2-diguaiacyl-1,3-propanediol (17), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (19), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (20), dihydroconiferyl alcohol (21), 4-acetylcatechol (22), 3',4',5'-trihydroxyacetophenone (23), 3,4-dihydroxy-2-methylbenzaldehyde (24), protocatechuic acid (25), 4-(dimethoxymethyl)pyrocatechol (26), tyrosol (27), isofraxidin (28), and 4-hydroxycatechol (29). One sesquiterpene, phaseic acid (30), which is a known metabolite of the phytohormone abscisic acid, was also isolated from MS-EtOAc. The antioxidant activities of MS-EtOAc (IC(50) = 75.5 μg/mL) and the pure isolates (IC(50) ca. 68-3000 μM) were comparable to that of vitamin C (IC(50) = 40 μM) and the synthetic commercial antioxidant butylated hydroxytoluene (IC(50) = 3000 μM), in the diphenylpicrylhydrazyl radical scavenging assay. The current study advances scientific knowledge of maple syrup constituents and suggests that these diverse phytochemicals may impart potential health benefits to this natural sweetener.

Further Investigation Into Maple Syrup Yields Three New Lignans, a New Phenylpropanoid, and Twenty-Six Other Phytochemicals

PubMed Central

LI, LIYA; SEERAM, NAVINDRA P.

2011-01-01

Maple syrup is made by boiling the sap collected from certain maple (Acer) species. During this process, phytochemicals naturally present in tree sap are concentrated in maple syrup. We previously reported 23 phytochemicals from a butanol extract of Canadian maple syrup (MS-BuOH). Here we report the isolation and identification of 30 additional compounds (1–30) from its ethyl acetate extract (MS-EtOAc) not previously reported from MS-BuOH. Of these, 4 compounds are new (1–3, 18) and 20 compounds (4–7, 10–12, 14–17, 19–20, 22–24, 26, 28–30) are being reported from maple syrup for the first time. The new compounds include 3 lignans and 1 phenylpropanoid: 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4′-hydroxy-3′-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one (1), (erythro, erythro)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (2), (erythro, threo)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (3) and 2,3-dihydroxy-1-(3,4-dihydroxyphenyl)-1-propanone (18), respectively. In addition, 25 other phenolic compounds were isolated including (threo, erythro)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (4), (threo, threo)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3-methoxyphenyl]-1,2,3-propanetriol (5), threo-guaiacylglycerol-β-O-4′-dihydroconiferyl alcohol (6), erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol (7), 2-[4-[2,3-dihydro-3-(hydroxymethyl)-5-(3-hydroxypropyl)-7-methoxy-2-benzofuranyl]-2,6-dimethoxyphenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (8), acernikol (9), leptolepisol D (10), buddlenol E (11), (1S,2R)-2-[2,6-dimethoxy-4-[(1S,3aR,4S,6aR)-tetrahydro-4-(4-hydroxy-3,5-dimethoxyphenyl)-1H,3H-furo[3,4-c]furan-1-yl]phenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (12), syringaresinol (13), isolariciresinol (14), icariside E4 (15), sakuraresinol (16), 1,2-diguaiacyl-1,3-propanediol (17), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (19), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (20), dihydroconiferyl alcohol (21), 4-acetylcatechol (22), 3′,4′,5′-trihydroxyacetophenone (23), 3,4-dihydroxy-2-methylbenzaldehyde (24), protocatechuic acid (25), 4-(dimethoxymethyl)-pyrocatechol (26), tyrosol (27), isofraxidin (28) and 4-hydroxycatechol (29). One sesquiterpene, phaseic acid (30), which is a known metabolite of the phytohormone, abscisic acid, was also isolated from MS-EtOAc. The antioxidant activities of MS-EtOAc (IC50 = 75.5 μg/mL), and the pure isolates (IC50 ca. 68–3000 μM) were comparable to vitamin C (IC50 = 40 μM) and the synthetic commercial antioxidant, butylated hydroxytoluene (IC50 = 3000 μM), in the diphenylpicrylhydrazyl radical scavenging assay. The current study advances scientific knowledge of maple syrup constituents and suggest that these diverse phytochemicals may impart potential health benefits to this natural sweetener. PMID:21675726