ErbB family of the receptor protein-tyrosine kinase plays an important role in the progression of human cancers including breast cancer. Finding protein-tyrosine phosphatase (PTPs) that can specifically regulate the function of ErbB should help design novel therapies for treatment. By performing a small interfering RNA screen against 43 human PTPs, we find that knockdown of protein-tyrosine phosphatase PTPN9 significantly increases ErbB2 tyrosyl phosphorylation in the SKBR3 breast cancer cell line. In addition, knockdown of PTPN9 expression also enhances tyrosyl phosphorylation of the ErbB1/epidermal growth factor receptor (EGFR) in the MDA-MB-231 breast cancer cell line. Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR. To test whether ErbB2 and EGFR are substrates of PTPN9, PTPN9 WT, and a substrate trapping mutant (PTPN9 DA) are overexpressed in SKBR3 and MDA-MB-231 cells. Compared with vector control, expression of PTPN9 WT significantly inhibits whereas expression of PTPN9 DA dramatically enhances tyrosyl phosphorylation of ErbB2 and EGFR, respectively. In contrast, expression of PTPN9 WT or DA mutant does not affect tyrosyl phosphorylation of ErbB3 and Shc. Importantly, coimmunoprecipitation and glutathione S-transferase fusion protein pulldown experiments show that tyrosol-phosphorylated ErbB2 or EGFR is preferentially associated with PTPN9 DA compared with PTPN9 WT, indicating that ErbB2 and EGFR are substrates of PTPN9. Furthermore, PTPN9 WT expression specifically impairs EGF-induced STAT3 and STAT5 activation, and inhibits the cell growth in soft agar. Last, PTPN9 WT expression also reduces invasion and MMP2 expression of MDA-MB-231 cells. Our data suggest PTPN9 as a negative regulator of breast cancer cells by targeting ErbB2 and EGFR and inhibiting STAT activation.

Olive oil phenolic compounds are potent antioxidants in vitro, but evidence for antioxidant action in vivo is controversial. We examined the role of the phenolic compounds from olive oil on postprandial oxidative stress and LDL antioxidant content. Oral fat loads of 40 mL of similar olive oils, but with high (366 mg/kg), moderate (164 mg/kg), and low (2.7 mg/kg) phenolic content, were administered to 12 healthy male volunteers in a cross-over study design after a washout period in which a strict antioxidant diet was followed. Tyrosol and hydroxytyrosol, phenolic compounds of olive oil, were dose-dependently absorbed (p<0.001). Total phenolic compounds in LDL increased at postprandial state in a direct relationship with the phenolic compounds content of the olive oil ingested (p<0.05). Plasma concentrations of tyrosol, hydroxytyrosol, and 3-O-methyl-hydroxytyrosol directly correlated with changes in the total phenolic compounds content of the LDL after the high phenolic compounds content olive oil ingestion. A 40 mL dose of olive oil promoted a postprandial oxidative stress, the degree of LDL oxidation being lower as the phenolic content of the olive oil administered increases. In conclusion, olive oil phenolic content seems to modulate the LDL phenolic content and the postprandial oxidative stress promoted by 40 mL olive oil ingestion in humans.

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.

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.

OBJECTIVE

The olive oil-rich Mediterranean diet protects against cardiovascular disease, which involves inflammatory processes. This study investigated the effects of phenolic compounds found in extra virgin olive oil on inflammatory mediator production by human mononuclear cells.

METHODS

Diluted human blood cultures were stimulated with lipopolysaccharide in the presence of phenolics (vanillic, p-coumaric, syringic, homovanillic and caffeic acids, kaempferol, oleuropein glycoside, and tyrosol) at concentrations of 10(-7) to 10(-4) M. Concentrations of the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 and of the inflammatory eicosanoid prostaglandin E2 were measured by enzyme-linked immunosorbent assay.

RESULTS

Oleuropein glycoside and caffeic acid decreased the concentration of interleukin-1beta. At a concentration of 10(-4) M, oleuropein glycoside inhibited interleukin-1beta production by 80%, whereas caffeic acid inhibited production by 40%. Kaempferol decreased the concentration of prostaglandin E2. At a concentration of 10(-4) M, kaempferol inhibited prostaglandin E2 production by 95%. No effects were seen on concentrations of interleukin-6 or tumor necrosis factor-alpha and there were no effects of the other phenolic compounds.

CONCLUSIONS

Some, but not all, phenolic compounds derived from extra virgin olive oil decrease inflammatory mediator production by human whole blood cultures. This may contribute to the antiatherogenic properties ascribed to extra virgin olive oil.

The elicitor-induced incorporation of phenylpropanoid derivatives into the cell wall and the secretion of soluble coumarin derivatives (phytoalexins) by parsley (Petroselinum crispum L.) suspension cultures can be potentiated by pretreatment of the cultures with 2,6-dichloroisonicotinic acid or derivatives of salicylic acid. To investigate this phenomenon further, the cell walls and an extracellular soluble polymer were isolated from control cells or cells treated with an elicitor from Phytophthora megasperma f. sp. glycinea. After alkaline hydrolysis, both fractions from elicited cells showed a greatly increased content of 4-coumaric, ferulic, and 4-hydroxybenzoic acid, as well as 4-hydroxybenzaldehyde and vanillin. Two minor peaks were identified as tyrosol and methoxytyrosol. The pretreatment effect is most pronounced at a low elicitor concentration. Its specificity was elaborated for coumarin secretion. When the parsley suspension cultures were preincubated for 1 d with 2,6-dichloroisonicotinic, 4- or 5-chlorosalicylic, or 3,5- dichlorosalicylic acid, the cells exhibited a greatly increased elicitor response. Pretreatment with isonicotinic, salicylic, acetylsalicylic, or 2,6-dihydroxybenzoic acid was less efficient in enhancing the response, and some other isomers were inactive. This increase in elicitor response was also observed for the above-mentioned monomeric phenolics, which were liberated from cell walls upon alkaline hydrolysis and for "lignin-like" cell wall polymers determined by the thioglycolic acid method. It was shown for 5-chlorosalicylic acid that conditioning most likely improves the signal transduction leading to the activation of genes encoding phenylalanine ammonia lyase and 4-coumarate: coenzyme A ligase. The conditioning thus sensitizes the parsley suspension cells to respond to lower elicitor concentrations. If a similar mechanism were to apply to whole plants treated with 2,6-dichloroisonicotinic acid, a known inducer of systemic acquired resistance, one can hypothesize that fungal pathogens might be recognized more readily and effectively.

Polyphenols reportedly exert physiological effects against diseases such as cancer, arteriosclerosis, hyperlipidemia and osteoporosis. The present study was designed to evaluate the effects of oleuropein, hydroxytyrosol and tyrosol, the major polyphenols in olives, on bone formation using cultured osteoblasts and osteoclasts, and on bone loss in ovariectomized mice. No polyphenols markedly affected the proliferation of osteoblastic MC3T3-E1 cells at concentrations up to 10μM. Oleuropein and hydroxytyrosol at 10 to 100μM had no effect on the production of type I collagen and the activity of alkaline phosphatase in MC3T3-E1 cells, but stimulated the deposition of calcium in a dose-dependent manner. In contrast, oleuropein at 10 to 100μM and hydroxytyrosol at 50 to 100μM inhibited the formation of multinucleated osteoclasts in a dose-dependent manner. Furthermore, both compounds suppressed the bone loss of trabecular bone in femurs of ovariectomized mice (6-week-old BALB/c female mice), while hydroxytyrosol attenuated H(2)O(2) levels in MC3T3-E1 cells. Our findings indicate that the olive polyphenols oleuropein and hydroxytyrosol may have critical effects on the formation and maintenance of bone, and can be used as effective remedies in the treatment of osteoporosis symptoms.

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.

Phenolic compounds in Spanish virgin olive oils were characterized by HPLC. Simple phenols such as hydroxytyrosol, tyrosol, vanillic acid, p-coumaric acid, ferulic acid, and vanillin were found in most of the oils. The flavonoids apigenin and luteolin were also found in most of the oils. The dialdehydic form of elenolic acid linked to tyrosol and hydroxytyrosol was also detected, as were oleuropein and ligstroside aglycons. The structure of a new compound was elucidated by MS and NMR as being that of 4-(acetoxyethyl)-1,2-dihydroxybenzene. Changes of phenolic compounds in virgin olive oils with maturation of fruits were also studied. Hydroxytyrosol, tyrosol, and luteolin increased their concentration in oils with maturation of fruits. On the contrary, glucoside aglycons diminished their concentration with maturation. No clear tendency was observed for the rest of the phenolic compounds identified.

Experimental and clinical evidence suggest that oxidative stress causes cellular damage, leading to functional alterations of the tissue. Free radicals may thus play an important role in the pathogenesis of a number of human diseases. Among pro-oxidant agents, oxidized LDL lead to the production of cytotoxic reactive species, e.g., lipoperoxides, causing tissue injury and various subsequent pathologies including intestinal diseases. Thus, to analyze the oxidative damage induced by oxidized LDL to intestinal mucosa, we evaluated morphological and functional changes induced in the human colon adenocarcinoma cell line, Caco-2. In addition, we examined the protective effects exerted by tyrosol, 2-(4-hydroxyphenyl)ethanol, the major phenolic compound present in olive oil. Caco-2 cell treatment (24 and/or 48 h) with oxidized LDL (0.2 g/L) resulted in cytostatic and cytotoxic effects characterized by a series of morphological and functional alterations: membrane damage, modifications of cytoskeleton network, microtubular disorganization, loss of cell-cell and cell-substrate contacts, cell detachment and cell death. The oxidized LDL-induced alterations in Caco-2 cells were almost completely prevented by tyrosol which was added 2 h before and present during the treatments. Our results suggest that some biophenols, such as those contained in olive oil, may counteract the reactive oxygen metabolite-mediated cellular damage and related diseases, by improving in vivo antioxidant defenses.

In vitro studies have shown phenolics in olive oil to be strong radical scavengers. The absorption and elimination of two radiolabeled phenolic constituents of olive oil, hydroxytyrosol and tyrosol were studied in vivo using rats. Compounds were administered intravenously (in saline) and orally (in oil- and water-based solutions). For both compounds, the intravenously and orally administered oil-based dosings resulted in significantly greater elimination of the phenolics in urine within 24 h than the oral, aqueous dosing method. There was no significant difference in the amount of phenolic compounds eliminated in urine between the intravenous dosing method and the oral oil-based dosing method for either tyrosol or hydroxytyrosol. Oral bioavailability estimates of hydroxytyrosol when administered in an olive oil solution and when dosed as an aqueous solution were 99% and 75%, respectively. Oral bioavailability estimates of tyrosol, when orally administered in an olive oil solution and when dosed as an aqueous solution were 98% and 71%, respectively. This is the first study that has used a radiolabeled compound to study the in vivo biological fates of hydroxytyrosol and tyrosol.

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 microg/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 microg/ml) to exert rapid inhibition 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.

OBJECTIVE

To investigate the absorption of tyrosol and hydroxytyrosol from moderate and sustained doses of virgin olive oil consumption. The study also aimed to investigate whether these phenolic compounds could be used as biomarkers of virgin olive oil intake.

METHODS

Ingestion of a single dose of virgin olive oil (50 ml). Thereafter, for a week, participants followed their usual diet which included 25 ml/day of the same virgin olive oil as the source of raw fat.

METHODS

Unitat de Recerca en Farmacologia. Institut Municipal d'Investigació Mèdica (IMIM).

METHODS

Seven healthy volunteers.

RESULTS

An increase in 24 h urine of tyrosol and hydroxytyrosol, after both a single-dose ingestion (50 ml) and short-term consumption (one week, 25 ml/day) of virgin olive oil (P<0.05) was observed. Urinary recoveries for tyrosol were similar after a single dose and after sustained doses of virgin olive oil. Mean recovery values for hydroxytyrosol after sustained doses were 1.5-fold those obtained after a single 50 ml dose.

CONCLUSIONS

Tyrosol and hydroxytyrosol are absorbed from realistic doses of virgin olive oil. With regard to the dose-effect relationship, 24 h urinary tyrosol seems to be a better biomarker of sustained and moderate doses of virgin olive oil consumption than hydroxytyrosol.

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.

Microorganisms have evolved a complex signature of communication termed quorum sensing (QS), which is based on the exchange and sensing of low molecular- weight signal compounds. The ability to communicate within the microbial population gives the advantage to coordinate a groups behaviour leading to a higher fitness in the environment. The polymorphic fungus Candida albicans is an opportunistic human pathogen able to regulate virulence traits through the production of at least two QS signal molecules: farnesol and tyrosol. The ability to adopt multiple morphotypes and form biofilms on infected surfaces are the most important pathogenic characteristics regulated by QS and are of clinical relevance. In fact, traditional antimicrobial approaches are often ineffective towards these characteristics. Moreover, the intimate association between C. albicans and other pathogens, such as Pseudomonas aeruginosa, increases the complexity of the infection system. This review outlines the current knowledge on fungal QS and fungal-bacterial interactions emphasizing on C. albicans. Further investigations need to concentrate on the molecular mechanisms and the genetic regulation of these phenomena in order to identify putative novel therapeutic options.

The major phenolics from the polar fraction of virgin olive oil (caffeic acid, oleuropein, tyrosol and hydroxytyrosol) have well-established antioxidant activities but their effects on reactive nitrogen species and nitrergic neurotransmission have not been fully investigated. The three catechol compounds were active as scavengers of nitric oxide generated spontaneously from the decomposition of sodium nitroprusside (approximately 50% inhibition achieved at 75 microM), and had similar ability to scavenge chemically generated peroxynitrite, as determined by an alpha1-antiproteinase inactivation assay (67.2%-92.4% reduction when added at 1 mM). Tyrosol was less active in these tests, but does not possess the catechol functionality. Despite their ability to interact with chemically prepared nitric oxide, neither oleuropein nor hydroxytyrosol at 5 microM altered NO*-mediated relaxations of the nerve-stimulated rat anococcygeus preparation, but this may be because the nitrergic transmitter is protected from the effects of externally applied scavengers. In conclusion, the phenolics found in virgin olive oil possess ability to scavenge reactive oxygen and nitrogen species that are implicated in human pathologies, but their impact may be restricted to those species present in the extracellular environment.

BACKGROUND

Recently, the European Food Safety Authority approved a claim concerning the benefits of olive oil polyphenols for the protection of LDL from oxidation. Polyphenols could exert health benefits not only by scavenging free radicals but also by modulating gene expression.

OBJECTIVE

We assessed whether olive oil polyphenols could modulate the human in vivo expressions of atherosclerosis-related genes in which LDL oxidation is involved.

METHODS

In a randomized, crossover, controlled trial, 18 healthy European volunteers daily received 25 mL olive oil with a low polyphenol content (LPC: 2.7 mg/kg) or a high polyphenol content (HPC: 366 mg/kg) in intervention periods of 3 wk separated by 2-wk washout periods.

RESULTS

Systemic LDL oxidation and monocyte chemoattractant protein 1 and the expression of proatherogenic genes in peripheral blood mononuclear cells [ie, CD40 ligand (CD40L), IL-23α subunit p19 (IL23A), adrenergic β-2 receptor (ADRB2), oxidized LDL (lectin-like) receptor 1 (OLR1), and IL-8 receptor-α (IL8RA)] decreased after the HPC intervention compared with after the LPC intervention. Random-effects linear regression analyses showed 1) a significant decrease in CD40, ADRB2, and IL8RA gene expression with the decrease of LDL oxidation and 2) a significant decrease in intercellular adhesion molecule 1 and OLR1 gene expression with increasing concentrations of tyrosol and hydroxytyrosol in urine.

CONCLUSIONS

In addition to reducing LDL oxidation, the intake of polyphenol-rich olive oil reduces CD40L gene expression, its downstream products, and related genes involved in atherogenic and inflammatory processes in vivo in humans. These findings provide evidence that polyphenol-rich olive oil can act through molecular mechanisms to provide cardiovascular health benefits. This trial was registered at www.controlled-trials.com as ISRCTN09220811.

Colonization by the fungal pathogen Candida albicans varies significantly, depending upon the pH and availability of oxygen. Because of our interest in extracellular molecules as potential quorum-sensing molecules, we examined the physiological conditions which regulate the production of the aromatic alcohols, i.e., phenethyl alcohol, tyrosol, and tryptophol. The production of these fusel oils has been well studied for Saccharomyces cerevisiae. Our data show that aromatic alcohol yields for C. albicans are determined by growth conditions. These conditions include the availability of aromatic amino acids, the pH, oxygen levels, and the presence of ammonium salts. For example, for wild-type C. albicans, tyrosol production varied 16-fold merely with the inclusion of tyrosine or ammonium salts in the growth medium. Aromatic alcohol production also depends on the transcription regulator Aro80p. Our results are consistent with aromatic alcohol production-aromatic transaminases (gene products for ARO8 and ARO9), aromatic decarboxylase (ARO10), and alcohol dehydrogenase (ADH)-via the fusel oil pathway. The expression of ARO8, ARO9, and ARO10 is also pH dependent. ARO8 and ARO9 were alkaline upregulated, while ARO10 was alkaline downregulated. The alkaline-dependent change in expression of ARO8 was Rim101 independent, while the expression of ARO9 was Rim101 dependent.

It is generally believed that the French paradox is related to the consumption of red wine and not other varieties of wine, including white wine or champagne. Some recent studies have indicated that white wine could also be as cardioprotective as red wine. The present investigation compares the cardioprotective abilities of red wine, white wine, and their principal cardioprotective constituents. Different groups of rats were gavaged with red wine, white wine, resveratrol, tyrosol, and hydroxytyrosol. Red wine and its constituent resveratrol and white wine and its constituents tyrosol and hydroxytyrosol all showed different degrees of cardioprotection as evidenced by their abilities to improve postischemic ventricular performance, reduce myocardial infarct size and cardiomyocyte apoptosis, and reduce peroxide formation. It was discovered in this study that although each of the wines and their components increased the enzymatic activities of the mitochondrial complex (I-IV) and citrate synthase, which play very important roles in oxidative phosphorylation and ATP synthesis, some of the groups were more complex-specific in inducing the activity compared to the other groups. Cardioprotective ability was further confirmed by increased expression of phospho-Akt, Bcl-2, eNOS, iNOS, COX-1, COX-2, Trx-1, Trx-2, and HO-1. The results of this study suggest that white wine can provide cardioprotection similar to red wine if it is rich in tyrosol and hydroxytyrosol.

This study was conducted to determine whether the daily consumption for 84 days of tyrosol and hydroxytyrosol, the main olive oil phenolic compounds, and olive oil mill wastewater (OMWW), a byproduct of olive oil production, rich in micronutrients, may improve bone loss in ovariectomized rats (an experimental model of postmenopausal osteoporosis) and in ovariectomized rats with granulomatosis inflammation (a model set up for senile osteoporosis). As expected, an induced chronic inflammation provoked further bone loss at total, metaphyseal, and diaphyseal sites in ovariectomized rats. Tyrosol and hydroxytyrosol prevented this osteopenia by increasing bone formation ( p < 0.05), probably because of their antioxidant properties. The two doses of OMWW extracts had the same protective effect on bone ( p < 0.05), whereas OMWW did not reverse established osteopenia. In conclusion, polyphenol consumption seems to be an interesting way to prevent bone loss.

The paper presents a review of the scientific publications on Rhodiola rosea L. known for its adaptogenic characteristics. Biologically active substances salidroside, rosin, rosavin, rosarin and tyrosol, which are mainly found in plant rhizomes, demonstrate therapeutic effect. These active components effect the central nervous system by increasing the ability to concentrate, the mental and physical power; they are efficient in the asthenic states and improve general resistance of the cells and the organism against the harmful outer influence. They also prevent the heart system from stress and arrhythmias, and posses some antioxidant activity. Some data confirm that the Rhodiola rosea L. preparations stop the growth of the malignant tumors and metastases in the liver. Some preclinical and clinical data of the golden root preparations are discussed in the survey. The interaction of the herb with other medicines, its usage and effect, recommended doses, and its side effects are also reviewed in the paper.

In the present study, the antioxidant profile of olive oil antioxidants was investigated. Hydroxytyrosol and oleuropein are potent scavengers of hydroxyl radicals (OH*), peroxynitrite (ONOOH), and superoxide radicals (O(2)*(-)). Homovanillic alcohol, one of the main metabolites of hydroxytyrosol, and tyrosol are less potent scavengers of these reactive species. None of the olive oil antioxidants are good hypochlorous acid (HOCl) or hydrogen peroxide (H(2)O(2)) scavengers. Hydroxytyrosol efficiently protects against LDL oxidation in vitro and in vivo. However, no protective effect of hydroxytyrosol is usually demonstrated ex vivo against the oxidation of LDL isolated from humans after hydroxytyrosol consumption. The present study shows that this controversy is due to the isolation of LDL, which greatly reduces the protective effect of hydroxytyrosol against LDL oxidation. Hydroxytyrosol is an efficient scavenger of several free radicals. The physiological relevance of the high intrinsic antioxidant activity of hydroxytyrosol is illustrated by its protection against LDL oxidation.

Recent in vitro and in vivo studies suggest that the anti-inflammatory properties of extra virgin olive oil may be involved in the prevention of chronic degenerative diseases. In this study, the ability of olive oil phenols to influence the release of superoxide anions (O2-), prostaglandin E2 (PGE2) and tumor necrosis factor α (TNFα) and the expression of cyclooxygenase2 (COX2) in human monocytes, freshly isolated from healthy donors, was investigated. O2- were measured by superoxide dismutase-inhibitable cytochrome c reduction and PGE2 and TNFα production were determined in culture medium with appropriate enzyme immunoassay kits. COX2 mRNA and protein were evaluated by quantitative reverse transcription-polymerase chain reaction and Western immunoblotting, respectively. Treatment of monocytes for 24 h with 100 μM of hydroxytyrosol (3,4-DHPEA), tyrosol (p-HPEA) and their secoiridoid derivatives (3,4-DHPEA and p-HPEA linked to the dialdehydic form of elenolic acid: 3,4-DHPEA-EDA and p-HPEA-EDA, respectively) significantly (P<.05) inhibited the production of O2(-) as follows: 3,4-DHPEA (40%,), p-HPEA (9%), 3,4-DHPEA-EDA (25%) and p-HPEA-EDA (36%). Hydroxytyrosol also considerably reduced the expression of COX2 at both the mRNA and protein level (P<.05) and caused a clear dose-dependent reduction of PGE2 released into the culture medium (45% and 71% at 50 and 100 μM, respectively, P<.05). The COX2 mRNA was also efficiently inhibited by the secoiridoids. Moreover, it was shown that hydroxytyrosol increased the monocytes TNFα production. In addition to other chemopreventive properties, these results suggest that the health effects of olive oil phenols may be related to their ability to modulate the production of pro-inflammatory molecules, a property common to non-steroidal anti-inflammatory drugs.