Anti-angiogenic effects of oleacein and oleocanthal: New bioactivities of compounds from Extra Virgin Olive Oil.

Phenolic compounds play a key role in the health benefits of Extra Virgin Olive Oil (EVOO). Among these molecules, the focus has been recently put on (-)-oleocanthal and (-)-oleacein, for which anti-cancer and angiogenesis-related findings have been reported. Here, we explored the modulatory action of (-)-oleocanthal and (-)-oleacein on angiogenesis, the process by which new vessels are created from pre-existent ones, which is directly linked to tumor progression and other pathological conditions. Two in vivo models strongly sustained by angiogenesis, and an in vitro model of endothelial cells to study different steps of angiogenesis, were used. In vivo evidence pointed to the anti-angiogenic effects of both compounds in vivo. In vitro, (-)-oleacein and (-)-oleocanthal inhibited the proliferation, invasion, and tube formation of endothelial cells, and (-)-oleacein significantly repressed migration and induced apoptosis in these cells. Mechanistically, the compounds modulated signaling pathways related to survival and proliferation, all at concentrations of physiological relevance for humans. We propose (-)-oleacein and (-)-oleocanthal as good candidates for angioprevention and for further studies as modulators of angiogenesis in clinical interventions, and as interesting functional claims for the food industry. Chemical compounds studied in this article: Oleocanthal (PubChem CID: 11652416); Oleacein (PubChem CID: 18684078).

Synthesis of Analogs to A-Type Proanthocyanidin Natural Products with Enhanced Antimicrobial Properties against Foodborne Microorganisms.

Developing new types of effective antimicrobial compounds derived from natural products is of interest for the food industry. Some analogs to A-type proanthocyanidins have shown promising antimicrobial and antibiofilm activities against foodborne bacteria. We report herein the synthesis of seven additional analogs with NO2 group at A-ring and their abilities for inhibiting the growth and the biofilm formation by twenty-one foodborne bacteria. Among them, analog 4 (one OH at B-ring; two OHs at D-ring) showed the highest antimicrobial activity. The best results with these new analogs were obtained in terms of their antibiofilm activities: analog 1 (two OHs at B-ring; one OH at D-ring) inhibited at least 75% of biofilm formation by six strains at all of the concentrations tested, analog 2 (two OHs at B-ring; two OHs at D-ring; one CH3 at C-ring) also showed antibiofilm activity on thirteen of the bacteria tested, and analog 5 (one OH at B-ring; one OH at D-ring) was able to disrupt preformed biofilms in eleven strains. The description of new and more active analogs of natural compounds and the elucidation of their structure-activity relationships may contribute to the active development of new food packaging for preventing biofilm formation and lengthening the food shelf life.

Synthesis and hLDH Inhibitory Activity of Analogues to Natural Products with 2,8-Dioxabicyclo[3.3.1]nonane Scaffold.

Human lactate dehydrogenase (hLDH) is a tetrameric enzyme present in almost all tissues. Among its five different isoforms, hLDHA and hLDHB are the predominant ones. In the last few years, hLDHA has emerged as a therapeutic target for the treatment of several kinds of disorders, including cancer and primary hyperoxaluria. hLDHA inhibition has been clinically validated as a safe therapeutic method and clinical trials using biotechnological approaches are currently being evaluated. Despite the well-known advantages of pharmacological treatments based on small-molecule drugs, few compounds are currently in preclinical stage. We have recently reported the detection of some 2,8-dioxabicyclo[3.3.1]nonane core derivatives as new hLDHA inhibitors. Here, we extended our work synthesizing a large number of derivatives (42-70) by reaction between flavylium salts (27-35) and several nucleophiles (36-41). Nine 2,8-dioxabicyclo[3.3.1]nonane derivatives showed IC50 values lower than 10 µM against hLDHA and better activity than our previously reported compound 2. In order to know the selectivity of the synthesized compounds against hLDHA, their hLDHB inhibitory activities were also measured. In particular, compounds 58, 62a, 65b, and 68a have shown the lowest IC50 values against hLDHA (3.6-12.0 µM) and the highest selectivity rate (>25). Structure-activity relationships have been deduced. Kinetic studies using a Lineweaver-Burk double-reciprocal plot have indicated that both enantiomers of 68a and 68b behave as noncompetitive inhibitors on hLDHA enzyme.

Proanthocyanidins in Pruning Wood Extracts of Four European Plum (Prunus domestica L.) Cultivars and Their hLDHA Inhibitory Activity.

European plum tree (Prunus domestica L.) is cultivated in many countries for its delicious and nutritive fruit and, accordingly, certain amounts of wood (from pruning works) are generated every year. The main objective of this work was to value this agricultural woody residue, for which the chemical composition of pruning wood extracts from four European plum cultivars was investigated, and the human lactate dehydrogenase A (hLDHA) inhibitory activity of plum wood extracts and pure proanthocyanidins present in those extracts was measured. For the chemical characterization, total phenolic content and DPPH radical-scavenging assays and HPLC-DAD/ESI-MS analyses were performed, the procyanidin (-)-ent-epicatechin-(2α→O→7,4α→8)-catechin (4), the phenolic glucoside (-)-annphenone (3) and the flavan-3-ol catechin (1) being the major components of the wood extracts. Some quantitative and qualitative differences were found among plum cultivars, and the content of proanthocyanidins ranged from 1.51 (cv. 'Claudia de Tolosa') to 8.51 (cv. 'De la Rosa') mg g-1 of dry wood. For the hLDHA inhibitory activity, six wood extracts and six proanthocyanidins were evaluated by a UV spectrophotometric assay, compound 4 showing the highest inhibitory activity (IC50 3.2 µM) of this enzyme involved on the excessive production of oxalate in the liver of patients affected by the rare disease Primary Hyperoxaluria.

Effects of Oleacein, a New Epinutraceutical Bioproduct from Extra Virgin Olive Oil, in LPS-Activated Murine Immune Cells.

The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 µg/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2/HO-1 axis and the inhibition of JAK/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases.

(-)-Oleocanthal induces death preferentially in tumor hematopoietic cells through caspase dependent and independent mechanisms.

Olive oil is a key component of the highly cardiovascular protective Mediterranean diet. (-)-Oleocanthal (OLC) is one of the most interesting phenolics present in virgin olive oil, and is formed from secoiridoid ligustroside during the processing of olives to yield the oil. Anti-inflammatory and anti-oxidant properties were identified shortly after OLC isolation, followed by the discovery of anti-tumor activities in a few non-hematopoietic cell lineages. Because of the scarcity of tissues potentially targeted by OLC analyzed so far and the unresolved mechanism(s) for OLC anti-tumor properties, we used a panel of 17 cell lines belonging to 11 tissue lineages to carry out a detailed examination of targets and pathways leading to cell growth inhibition and death. We found that OLC inhibits cell proliferation and induces apoptotic death as revealed by sub-G1 cell cycle analyses and Annexin-V staining in all lineages analyzed except lung carcinoma cell lines. Hematopoietic tumor cell lines, untested until now, were the most sensitive to OLC treatment, whereas non-transformed cells were significantly resistant to cell death. The specificity of OLC-mediated caspase activation was confirmed by blocking experiments and the use of transfectants overexpressing anti apoptotic genes. OLC triggers typical mediators of the intrinsic apoptotic pathway such as production of reactive oxygen species and mitochondrial membrane depolarization (Δψm). Complete blockade of caspases, however, did not result in parallel abrogation of Annexin-V staining, thus suggesting that complex mechanisms are involved in triggering OLC-mediated cell death. Our results demonstrate that OLC preferentially targets hematopoietic tumor cell lines and support that cell death is mediated by caspase-dependent and independent mechanisms.

Lactate dehydrogenase A inhibitors with a 2,8-dioxabicyclo[3.3.1]nonane scaffold: A contribution to molecular therapies for primary hyperoxalurias.

Human lactate dehydrogenase A (hLDHA) is one of the main enzymes involved in the pathway of oxalate synthesis in human liver and seems to contribute to the pathogenesis of disorders with endogenous oxalate overproduction, such as primary hyperoxaluria (PH), a rare life-threatening genetic disease. Recent published results on the knockdown of LDHA gene expression as a safe strategy to ameliorate oxalate build-up in PH patients are encouraging for an approach of hLDHA inhibition by small molecules as a potential pharmacological treatment. Thus, we now report on the synthesis and hLDHA inhibitory activity of a new family of compounds with 2,8-dioxabicyclo[3.3.1]nonane core (23-42), a series of twenty analogues to A-type proanthocyanidin natural products. Nine of them (25-27, 29-34) have shown IC50 values in the range of 8.7-26.7 µM, based on a UV spectrophotometric assay, where the hLDHA inhibition is measured according to the decrease in absorbance of the cofactor ß-NADH (340 nm). Compounds 25, 29, and 31 were the most active hLDHA inhibitors. In addition, the inhibitory activities of those nine compounds against the hLDHB isoform were also evaluated, finding that all of them were more selective inhibitors of hLDHA versus hLDHB. Among them, compounds 32 and 34 showed the highest selectivity. Moreover, the most active hLDHA inhibitors (25, 29, 31) were evaluated for their ability to decrease the oxalate production by hyperoxaluric mouse hepatocytes (PH1, PH2 and PH3) in vitro, and the relative oxalate output at 24 h was 16% and 19 % for compounds 25 and 31, respectively, in Hoga1-/- mouse primary hepatocyte cells (a model for PH3). These values improve those of the reference compound used (stiripentol). Compounds 25 and 31 have in common the presence of two hydroxyl groups at rings B and D and an electron-withdrawing group (NO2 or Br) at ring A, pointing to the structural features to be taken into account in future structural optimization.

Ligstroside aglycon, an extra virgin olive oil secoiridoid, prevents inflammation by regulation of MAPKs, JAK/STAT, NF-κB, Nrf2/HO-1, and NLRP3 inflammasome signaling pathways in LPS-stimulated murine peritoneal macrophages.

Ligstroside aglycon (LA) is one of the main polyphenols in extra virgin olive oil (EVOO); nevertheless, it is scarcely investigated. The aim of this study was to evaluate the immunomodulatory and anti-inflammatory effects of LA on lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages, as well as the potential signaling pathways involved. Isolated macrophages were treated with LA (50, 25, and 12.5 µM) in the presence or absence of LPS (5 µg ml-1) for 18 h. Cell viability was determined using the sulforhodamine B (SRB) assay. Nitric oxide (NO) and pro-inflammatory cytokine production was analyzed by the Griess method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression of pro-inflammatory markers and signaling pathways were evaluated by western blot analysis. LA showed significant antioxidant and anti-inflammatory effects through decreasing oxidative stress markers such as NO production, inducible nitric oxide synthase (iNOS) and NADPH oxidase-1 (NOX-1) protein expression. Besides, LA was able to reduce pro-inflammatory cytokine levels and modulate cyclo-oxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGEs-1) protein overexpression. The mechanisms underlying these protective effects could be related via activation of nuclear factor (erythroid-derived 2)-like (Nrf2)/heme oxygenase 1 (HO-1) and inhibition of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinases (MAPKs), and Janus kinase/signal transducer and activation of transcription (JAK2/STAT3) signaling pathways. In addition, LA inhibited non-canonical and canonical activation of a nucleotide-binding (NOD)-like receptor (NLRP3) inflammasome. We conclude that LA showed significant antioxidant and anti-inflammatory activities in LPS-stimulated murine peritoneal macrophages. However, further in vivo studies are warranted to further investigate the bioactivity of this interesting compound that might be a promising natural agent for the treatment of immune-inflammatory diseases.

Biological effects of olive oil phenolic compounds on mitochondria.

Phenolic compounds derived from olive oil have beneficial health properties against cancer, neurodegenerative, and metabolic diseases. Therefore, there are discrepancies in their impact on mitochondrial function that result in changes in oxidative capacity, mitochondrial respiration, and energetic demands. This review focuses on the versatile role of oleuropein, a potent antioxidant that regulates the AMPK/SIRT1/mTOR pathway to modulate autophagy/mitophagy and maintain metabolic homeostasis.

Recovery and Seasonal Variation of Cinnamtannin B-1 from Laurel (Laurus nobilis L.) Pruning Wood Wastes.

Cinnamtannin B-1 (C-B1) is a commercially-available trimeric A-type procyanidin with remarkable cellular actions mainly derived from its high radical scavenging activity. C-B1 is the main phenolic compound of laurel wood, which has previously been isolated by a combination of conventional chromatographic techniques. The first aim of this work was to find laurel trees containing as much C-B1 as possible, and learn about the influence of variables, such as gender and harvest time, on the production of C-B1 by the tree. It was found that all studied trees tend to give higher C-B1 percentages in the May-July period, from 6 % to 18 %, and lower ones around March (spring) and November (fall), from 1 % to 8 %. In a general way, it also seems that the female trees tend to produce a bit more C-B1 (from 2.8 % to 17.3 %) than male ones (from 1.7 % to 13.4 %). In addition, eight minor phenolic compounds [(-)-ent-catechin (1), (-)-ent-epicatechin-(4α→8)-ent-epicatechin (2), (epi)catechin-(4→8)-(epi)afzelechin-(4→8)-(epi)catechin (3), (+)-epiafzelechin-(4ß→8)-epicatechin (4), (-)-epicatechin (5), (-)-afzelechin-(4α→8)-epicatechin (6), (epi)afzelechin-(4→8)-(epi)afzelechin-(4→8)-(epi)catechin (7) and (+)-epicatechin-(4ß→8,2ß→O-7)-epicatechin-(4ß→8)-catechin (C-D1)] were found and quantified in the ethyl acetate extract of the wood samples. The second aim of this work was to improve the recovery of C-B1 from laurel wood. The use of the fast centrifugal partition chromatography (FCPC) technique has allowed for a recovery of 96 % of a technical-grade C-B1 (64 % in a previous protocol using conventional column chromatography on silica gel and size-exclusion chromatography).

Small Molecule-Based Enzyme Inhibitors in the Treatment of Primary Hyperoxalurias.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism. PHs classification based on gene mutations parallel a variety of enzymatic defects, and all involve the harmful accumulation of calcium oxalate crystals that produce systemic damage. These geographically widespread rare diseases have a deep impact in the life quality of the patients. Until recently, treatments were limited to palliative measures and kidney/liver transplants in the most severe forms. Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1. However, small molecule drugs have classically been preferred since they benefit from experience and have better pharmacological properties. The development of small molecule inhibitors designed against key enzymes of glyoxylate metabolism is on the focus of research. Enzyme inhibitors are successful and widely used in several diseases and their pharmacokinetic advantages are well known. In PHs, effective enzymatic targets have been determined and characterized for drug design and interesting inhibitory activities have been achieved both in vitro and in vivo. This review describes the most recent advances towards the development of small molecule enzyme inhibitors in the treatment of PHs, introducing the multi-target approach as a more effective and safe therapeutic option.

(-)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation.

The antioxidant and anti-inflammatory responses of (-)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulation of histones were studied. Met-OLE inhibited LPS-induced intracellular reactive oxygen species (ROS) and nitrite (NO) production and decreased the overexpression of the pro-inflammatory enzymes COX-2, mPGES-1 and iNOS in murine macrophages. In addition, met-OLE was able to significantly decrease the activation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs) and blocked canonical and non-canonical inflammasome signaling pathways. On the contrary, met-OLE upregulated haem oxigenase 1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) expression in treated cells. Finally, met-OLE pretreated spleen cells counteracted LPS induction, preventing H3K18 acetylation or H3K9 and H3K27 demethylation. Overall, these results provide novel mechanistic insights into the beneficial effects of met-OLE regarding the regulation of the immune-inflammatory response through epigenetic changes in histone markers. This revealing evidence suggests that the methylated metabolite of OLE may contribute significantly to the beneficial effects that are associated with the secoiridoid-related compound and the usual consumption of EVOO.

Gene flow between diploid and tetraploid junipers - two contrasting evolutionary pathways in two Juniperus populations.

BACKGROUND: Gene flow and polyploidy have been found to be important in Juniperus evolution. However, little evidence has been published elucidating the association of both phenomena in juniper taxa in the wild. Two main areas were studied in Spain (Eastern Iberian Range and Sierra de Baza) with both diploid and tetraploid taxa present in sympatry. Gene flow and ploidy level were assessed for these taxa and the resulted offspring. RESULTS: Twenty-two allo-triploid hybrids between J. sabina var. sabina and J. thurifera were found in the Eastern Iberian Range population. However, in the Sierra de Baza population no triploids were found. Instead, 18 allo-tetraploid hybrids between two tetraploid taxa: J. sabina var. balkanensis and J. thurifera were discovered. High genetic diversity was exhibited among the tetraploid hybrids at Sierra de Baza, in contrast to the genetically identical triploid hybrids at the Eastern Iberian Range; this suggests meiotic difficulties within the triploid hybrids. In addition, unidirectional gene flow was observed in both studied areas. CONCLUSION: Polyploidy and hybridization can be complementary partners in the evolution of Juniperus taxa in sympatric occurrences. Juniperus was shown to be an ideal coniferous model to study these two phenomena, independently or in concert.

Thermodynamic Stability of Flavylium Salts as a Valuable Tool To Design the Synthesis of A-Type Proanthocyanidin Analogues.

A convenient method to synthesize A-type proanthocyanidin analogues from flavylium salts and π-nucleophiles has been developed. It was found that the thermodynamic stability of the starting flavylium salt, assessed by the measurement of the apparent acidity constant ( K'a), was the key parameter to design effective one-pot reactions between flavylium salts and nucleophiles such as phloroglucinol and (+)-catechin. When flavylium salts have a p K'a value of 1.7 or lower, the synthesis of the corresponding 2,8-dioxabyciclo[3.3.1]nonane derivative was properly achieved.

Synthesis and Evaluation of Antimicrobial and Antibiofilm Properties of A-Type Procyanidin Analogues against Resistant Bacteria in Food.

Natural A-type procyanidins have shown very interesting biological activities, such as their proven antiadherence properties against pathogenic bacteria. In order to find the structural features responsible for their activities, we describe herein the design and synthesis of six A-type procyanidin analogues and the evaluation of their antimicrobial and antibiofilm properties against 12 resistant bacteria, both Gram positive and Gram negative, isolated from organic foods. The natural A-type procyanidin A-2, which had known antiadherence activity, was also tested as a reference compound for the comparative studies. Within the series, analogue 4, which had a NO2 group on ring A, showed the highest antimicrobial activity (MIC of 10 µg/mL) and was one of the best molecules at preventing biofilm formation (up to 40% decreases at 100 µg/mL) and disrupting preformed biofilms (up to 40% reductions at 0.1 µg/mL). Structure-activity relationships are also analyzed.

Phytochemicals and Biological Activities of Laurel Tree (Laurus nobilis).

This review summarizes the chemical composition reported up to date on Laurus nobilis L. (Lauraceae), an evergreen shrub or tree cultivated for its aromatic leaves and ornamental interest. It has been focused on non-volatile phytochemicals such as sesquiterpene lactones, flavonoids and proanthocyanidins, among others. Moreover, biological activities of laurel extracts and pure compounds have also been reviewed.

Effect of Methyl, Hydroxyl, and Chloro Substituents in Position 3 of 3',4',7-Trihydroxyflavylium: Stability, Kinetics, and Thermodynamics.

The effect of methyl, hydroxyl, and chloride substituents in position 3 of the 3',4',7-trihydroxyflavylium core structure was studied. The stability, relative energy of each of chemical species (thermodynamics), and their rates of interconversion (kinetics) are very dependent on these substituents. By comparing the mole fraction distribution at equilibrium of the three multistate systems with the parent 3',4',7-trihydroxyflavylium, introduction of a methyl substituent in position 3 increases the mole fraction of hemiketal at the expense of the trans-chalcone and increases the hydration rate very significantly; a hydroxyl substituent in position 3 gives rise to a degradation process, as observed in anthocyanidins. In the case of 3-chloro-3',4',7-trihydroxyflavylium, a dramatic increase of the flavylium cation acidity was observed and a photochromic system can be operated upon irradiation of the respective trans-chalcone in 1 m HCl. According to the photochromic response of 3,3',4',7-tetrahydroxyflavylium and 3',4',7-trihydroxyflavylium, some requirements for a good photochromic performance are discussed.

Antihyperlipidemic Effects of Sour Cherries Characterized by Different In Vitro Antioxidant Power and Polyphenolic Composition.

The aims of the present study were to clarify in vivo effects of three sour cherry cultivars characterized by different polyphenolic composition in hyperlipidemic animals in a short term experiment. The three different sour cherry cultivars were chosen based on their total in vitro antioxidant capacity, total polyphenolic, monomeric anthocyanin and flavonoid content. Male Wistar rats were divided randomly into eight groups: rats kept on normal diet (control) and normal diet supplied with sour cherry powder of one of the three cultivars; others were kept on fat-rich diet and fat-rich diet supplied with sour cherry powder prepared from one of the three cultivars. The treatment lasted 10 days. Lyophilized sour cherry administered in the diet decreased both total cholesterol and LDL cholesterol levels, and increased the HDL cholesterol concentration in sera of hyperlipidemic animals. Significant differences were found in the efficacy of different sour cherry cultivars in case of hyperlipidemia. Sour cherries characterized by higher polyphenol content seem to have a more pronounced effect on serum cholesterol levels. Our results suggest that besides anthocyanins, colourless polyphenols also have lipid lowering effect.

Evaluation of the antiaggregant activity of ascorbyl phenolic esters with antioxidant properties

Beneficial effects of the antioxidant L-ascorbic acid (Asc) in human health are well known. Its particular role in hemostasis deserves further consideration, since it has been described a dose-dependent effect of Asc in platelet activity. Contrary, it has been demonstrated that phenolic compounds have inhibitory effects on platelet aggregation stimulated by the physiological agonist thrombin (Thr). Here, we have evaluated the actions of three synthetic phenolic esters of Asc: L-ascorbyl 6-protocatechuate (Prot Asc), L-ascorbyl 6-gallate (Gal Asc), and L-ascorbyl 6-caffeate (Caf Asc). All these Asc derivatives exhibited greater radical scavenging activity than Asc, and in experiments using human platelets from healthy subjects, they do not evoke changes in platelet viability upon their administration. Nevertheless, these compounds altered platelet calcium homeostasis in response to Thr, although Prot Asc induced a smaller effect than Gal Asc, Caf Asc, and Asc. As a consequence, platelet aggregation was also impaired by these compounds, reporting Prot Asc and Caf Asc a weaker antiaggregant action than Gal Asc and Asc. Treatments with Gal Asc and Caf Asc altered in larger extent the phosphorylation pattern of pp60Src and mammalian target of rapamycin (mTOR) evoked by stimulating human platelets with Thr. Summarizing, Prot Asc is the ascorbyl phenolic ester with the strongest antioxidant properties and weakest antiaggregant actions, and its use as antioxidant may be safer than the rest of derivatives in order to prevent thrombotic alteration in patients that need treatment with antioxidant therapies (AU)

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

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-ß-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%).