The catalytic efficiency of birnessite in the removal of catechol, hydroxytyrosol, methylcatechol and m-tyrosol, four phenols commonly present in polluted wastewaters, was studied in mono-substrate solutions or in mixtures of two, three, and four substrates. In single phenolic solutions the transformation order of phenols was catechol>hydroxytyrosol)methylcatechol>m-tyrosol. With phenolic mixtures different responses were observed and the amount of each phenol transformed and the crossing effects among the various phenols depended on the type and number of phenols present in the mixture. In particular, general inhibitory effects were observed for hydroxytyrosol and m-tyrosol that were transformed less when present in combination with the other phenols. By contrast the effects by the presence of more than one phenol were basically annulled for catechol and methylcatechol at 24 h incubation in all the mixtures. A simultaneous, but often no stoichiometric, release of soluble Mn2+ in the reaction mixtures occurred. The multi-substrate systems were designed to mimic birnessite-mediated oxidative processes that could occur under field conditions. Therefore they could be of great interest to environmental and soil science. The use of birnessite as a potential tool for an effective detoxification and recovery of phenol-polluted systems could be also envisaged.

The aim of the present study is to highlight volatile and targeted non-volatile bioactive compounds in Nuragus wines, as a part of Italian DOC (Controlled Origin Designation) white wines. So far there has not been any systematic study of the chemical compositions and antioxidant activity of this monovarietal wine. Phenolic compounds, volatiles and organic acids were analysed and antioxidant capacity was assessed by spectrophotometric assays. Chromaticity coordinates and technological parameters (alcohol, reducing sugars, pH, total and volatile acidity) were also evaluated. Gallic acid (128±87mg/L), trans-caftaric acid (81±27mg/L) and tyrosol (25±8mg/L) were the most abundant phenolic compounds. The major headspace volatiles were isoamyl alcohol (35.8-76.6%) and 2-phenylethanol (5.9-24.9%). In the wine extracts, the most abundant were 2-phenylethanol (12.3-40.0%), 4-hydroxy-2-phenylethanol (12.5-33.3%), diethyl succinate (5.8-30.3%), (Z)-octadec-9-en-1-ol (5.9-18.3%) and tryptophol (2.8-15.6%). Nuragus wines exhibited an excellent antioxidant capacity. The data obtained may help Nuragus wine producers to promote this monovarietal wine as a valid complement associated with the Mediterranean diet.

In this study we elucidate antioxidative properties of the mushroom Ganoderma applanatum (Pers.) Pat. enhanced by submerged culture with para-hydroxyphenolic compounds and tea leaf extracts. The tea extract has been shown to increase to different extents the antioxidative efficiency of para-substituted phenolics, with the most profound effect for 2-(4-hydroxyphenyl)ethane-1-ol (tyrosol). Within the range of physiological concentrations, the symbatic correlation of the antioxidative action of the fungal samples with the volume of tea extract in the submerged culture medium was observed. We propose an approach to obtain, through the use of black tea extracts as the nutrient medium component, large amounts of G. applanatum seeding mycelia; the extract exerts a profound positive effect on the level of phenolic-type antioxidants.

The effect of phenolic antioxidants (dihydroquercetin, p-tyrosol, dibornol) on the morphology, functions, and redox processes in the reproductive cells of male rats was studied on the model of experimental pathospermia. All antioxidants reduced the percentage of degenerative forms of spermatozoa. Dibornol was most effective. Dihydroquercetin and p-tyrosol did not increase the total number of spermatozoa and the percentage of their mobile forms. These indicators were improved only by dibornol. After administration of all test drugs, the antioxidant potential of spermatozoa increased and did not significantly differ from the baseline values.

Major phenolic compounds from olive oil (ArOH-EVOO), oleuropein (Ole), tyrosol (Tyr), and p-coumaric acid (p-Cou), are known for their antioxidant and neuroprotective properties. We previously demonstrated that their combination could potentiate their antioxidant activity in vitro and in cellulo. To further our knowledge of their electron-transfer properties, Ole, Tyr, and p-Cou underwent a spectroelectrochemical study, performed either individually or in equimolar mixtures. Two mixtures (Mix and Mix-seq) were prepared in order to determine whether distinct molecules could arise from their simultaneous or sequential oxidation. The comparison of Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS²) profiles highlighted the presence of specific oxidized products found in the mixes. We hypothesized that they derived from the dimerization between Tyr and Ole or p-Cou, which have reacted either in their native or oxidized forms. Moreover, Ole regenerates when the Mix undergoes oxidation. Our study also showed significant neuroprotection by oxidized Ole and oxidized Mix against H₂O₂ toxicity on SK-N-SH cells, after 24 h of treatment with very low concentrations (1 and 5 nM). This suggests the putative relevant role of oxidized Ole products to protect or delay neuronal death.

Tyrosol is a pharmacologically active phenolic compound widely used in the pharmaceutical and chemical industries. Microbial fermentation has potential value as an environmentally friendly approach to tyrosol production but suffers from low tyrosol yields and the need for expensive media additives. In this study, Escherichia coli MG1655 was modified by integrating an E. coli codon-optimized version of the Saccharomyces cerevisiae phenylpyruvate decarboxylase gene, named ARO10*, into the lacI locus. The resulting strain (YMGA*) produced 0.14 mM tyrosol from 2% glucose without the need for expensive media supplements. Subsequent deletion of E. coli genes designed to eliminate competing metabolic pathways (feaB, pheA, tyrB) or undesirable gene regulation (tyrR) produced a strain (YMGA*R) that produced 3.11 mM tyrosol. Tyrosol production was then increased to 10.92 mM by increasing the ARO10* copy number to five copies (strain YMG5A*R). Finally, tyrosol production was increased to 28 mM (ca. 3.9 g/L) by optimizing fermentation conditions in a 5-L fermenter. Engineering a productive E. coli strain with high tyrosol titer from glucose using a medium that does not require added amino acids, inducer, or antibiotic, which provides a solid basis to produce tyrosol through microbial fermentation.

In this work, different commercial extra-virgin olive oils (EVOO) were subjected to in vitro gastrointestinal digestion and the changes in bioactive compounds were evaluated by ultra-high-pressure liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, using untargeted metabolomics. As expected, raw EVOO samples were abundant in total sterols (on average: 3007.4 mg equivalents/kg) and tyrosol equivalents (on average: 334.1 mg equivalents/kg). However, the UHPLC-QTOF screening allowed us to annotate 310 compounds, with a large abundance of sterols (219 compounds), followed by polyphenols (67 compounds) and terpenoids. The in vitro gastrointestinal digestion was found to affect the phytochemical composition of the different EVOO samples. In particular, both unsupervised and supervised statistics depicted the modifications of the bioactive profile following gastric and pancreatic phases. Overall, the compounds which resulted as the most affected by the in vitro digestion were flavonoids (cyanidin and luteolin equivalents), whilst relatively high % bioaccessibility values were recorded for tyrosol equivalents during the pancreatic phase (on average, 66%). In this regard, oleuropein-aglycone (i.e., the major phenolic compound in EVOO) was converted to hydroxytyrosol, moving from an average value of 1.3 (prior to the in vitro digestion) up to 9.7 mg equivalents/kg during the pancreatic step. As proposed in the literature, the increase in hydroxytyrosol might be the result of the combined effect of lipase(s) activity and acidic conditions. Taken together, the present findings corroborate the suitability of untargeted metabolomics coupled to in vitro digestion methods to investigate the bioaccessibility of phenolic compounds. In this regard, a significant impact of in vitro gastrointestinal digestion on polyphenolic profiles has been detected, thus suggesting the need to account for actual bioaccessibility values rather than just considering the amounts in the raw commodity.

Interleukin 1 beta (IL-1β) induced platelet activating factor (PAF) synthesis in U-937 cells through stimulation of acetyl-CoA:lysoPAF-acetyltransferase (lyso PAF-AT) at 3 h and DTT-independentCDP-choline-1-alkyl-2-acetyl-sn-glycerol cholinophosphotransferase (PAF-CPT) at 0.5 h. The aim of this study was to investigate the effect of tyrosol (T), resveratrol (R) and their acetylated derivatives(AcDs) which exhibit enhanced bioavailability, on PAF synthesis in U-937 after IL-1β stimulation. The specific activity of PAF enzymes and intracellular levels were measured in cell homogenates. T and R concentration capable of inducing 50% inhibition in IL-1β effect on lyso PAF-AT was 48 μΜ ± 11 and 157 μΜ ± 77, for PAF-CPT 246 μΜ ± 61 and 294 μΜ ± 102, respectively. The same order of concentration was also observed on inhibiting PAF levels produced by IL-1β. T was more potent inhibitor than R (p<0.05). AcDs of T retain parent compound inhibitory activity, while in the case of R only two AcDs retain the activity. The observed inhibitory effect by T,R and their AcDs, may partly explain their already reported beneficial role.

In continuation of our search for new antibacterial and antioxidant metabolites from sponge-derived fungi, one new tyrosol derivative, hypocrol A (1), together with four known congeners, trichodenol B (2), 4-hydroxyphenethyl acetate (3), 4-hydroxyphenethyl tetradecanoate (4) and 1-oleyltyrosol (5), was isolated from the strain Hypocrea koningii PF04. Their planar structures were unequivocally elucidated by spectroscopic methods and comparison with the literature data. All the compounds displayed weak antibacterial activities against Staphylococcus aureus, methicillin-resistant S. aureus and Escherichia coli, whereas compounds 1 and 2 exhibited a moderate antioxidant efficacy in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay with IC50 values of 48.5 and 97.4 μg/mL, respectively.

Nanocomposites containing antimicrobial agents and calcium phosphates have been developed. Thus, this study assessed the effects of two compounds containing silver nanoparticles (AgNPs) and β-calcium glycerophosphate (CaGP), associated or not with tyrosol (TYR), against planktonic cells and biofilms of Candida albicans and Streptococcus mutans. The nanocompounds were synthesized through chemical and 'green' processes and characterized by scanning electron microscopy. The minimum and fractional inhibitory concentrations of each compound were determined for planktonic cells. Next, 24-h single biofilms of C. albicans and S. mutans were treated for 24 h with the nanocompounds alone or in combination with TYR, and the antibiofilm effect was assessed through enumeration of colony forming units. Biofilm data were statistically examined using one-way ANOVA and the Kruskal-Wallis test (α = 0.05). The chemically synthesized nanocompound in combination with TYR demonstrated a synergistic effect against planktonic cells of C. albicans and S. mutans. For the nanocompound obtained through the 'green' route associated with TYR, a synergistic effect was observed only against C. albicans. For biofilms, only the combination obtained through the 'green' route + TYR demonstrated a synergistic effect against C. albicans. Our results may contribute to the development of oral care products containing AgNPs-CaGP and TYR to combat oral infections.

The number of effective therapeutic strategies against biofilms is limited; development of novel therapies is urgently needed to treat a variety of biofilm-associated infections. Quorum sensing is a special form of microbial cell-to-cell communication that is responsible for the release of numerous extracellular molecules, whose concentration is proportional with cell density. Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) have a pivotal role in morphogenesis, biofilm formation, and virulence. Farnesol can mediate the hyphae-to-yeast transition, while tyrosol has the opposite effect of inducing transition from the yeast to hyphal form. A number of questions regarding Candida quorum sensing remain to be addressed; nevertheless, the literature shows that farnesol and tyrosol possess remarkable antifungal and anti-biofilm effect at supraphysiological concentration. Furthermore, previous in vitro and in vivo data suggest that they may have a potent adjuvant effect in combination with certain traditional antifungal agents. This review discusses the most promising farnesol- and tyrosol-based in vitro and in vivo results, which may be a foundation for future development of novel therapeutic strategies to combat Candida biofilms.

Keywords: Candida; biofilm; combination; farnesol; therapy; tyrosol.

Tyrosol galactoside (TG) is a new candidate anti-fatigue agent under development. In order to have a good understanding of its pharmacokinetic characters, the paper describes the dose-dependent pharmacokinetics of TG in rats after oral and intravenous administration. TG was rapidly absorbed after oral administration and cleared with first-order rate, for the plasma half-life was independent of dose. C(max) and AUC(0-infinity) after both intravenous and oral dosing were all linearly correlated with the dose, as the regression correlation coefficient (R) was 0.998, 0.989 and 0.994 for AUC(0-infinity) (i.v., P < 0.01) AUC(0-infinity) (i.g., P < 0.01) and C(max) (i. g., P < 0.01), respectively. However, these parameters increased less than proportionally with increasing dose. In addition, the apparent volume of distribution (Vd) and the apparent clearance (Cl) seemed to be affected by the dose.

In this study, the effects of some additives [manganese (III) oxide (Mn3O4), Cu(+2), Fe(0) and potassium iodate (KIO3)] and some radical scavengers [sodium carbonate (Na2CO3), perfluorohexane (C6F14) and t-butyl alcohol (C4H10O)] on the sonication of olive mill effluent wastewater (OMW) were investigated since the wastewaters of this industry are removed with low efficiencies. The maximum total phenol and total aromatic amines (TAAs) removal efficiencies were 88% and 79%, respectively, at 60°C with only 150 min sonication. The maximum phenol removal was found as 98% with 19 mg L(-1) perfluorohexane and 5 mg L(-1) Fe(0) while the maximum TAAs removal was 99% with 16 mg L(-1) KIO3. Catechol, tyrosol, quercetin, caffeic acid, 4-methyl catechol, 2-phenylphenol (2-PHE) and 3-phenyl phenol (3-PHE) were detected as phenol intermediates while trimethlyaniline, aniline, o-toluidine, o-anisidine, dimethylaniline, ethylbenzene and durene were identified as TAAs in the OMW. The maximum acute toxicity removals were 96% and 99% in Vibrio fischeri and Daphnia magna, respectively. Total phenol, TAAs and the toxicity in an OMW were removed efficiently and cost-effectively through sonication.

Zirconium dioxide (zirconia, ZrO2)-doped TiO2 (TiO2/ZrO2) nanocomposite was used for the photocatalytic oxidation of pollutant parameters [COD components (CODtotal, CODdissolved and CODinert)], polyphenols (catechol, 3-hydroxybenzoic acid, tyrosol and 4-hydroxybenzoic acid) and total polyaromatic amines [aniline, 4-nitroaniline, o-toluidine and o-anisidine] from the olive mill effluent wastewaters at different operational conditions such as at different mass ratios of ZrO2 (50, 25, 14, 10 and 5 wt%) in the TiO2/ZrO2 nanocomposite, at different TiO2/ZrO2 photocatalyst concentrations (1, 4, 15 and 50 mg/L) and pH values (4.0-7.0-10.0) under 300 W UV irradiations, respectively. Under the optimized conditions (pH = 4.6, 15 mg/L ZrO2/TiO2 nanocomposite with a ZrO2 mass ratio of 14 wt%, 300 W UV light, after 60 min photooxidation time, at 21°C), the maximum CODdissolved, total phenol and total aromatic amines photooxidation yields were 99%, 89% and 95%, respectively. High pollutant removal (89%) yields after sequential five times utilization of ZrO2/TiO2 nanocomposite show that this catalyst can be effectively used commercially in the treatment of olive mill effluent.

Oleuropein, tyrosol, squalene and the fraction of sterols and triterpenoid dialcohols from the unsaponifiable fraction obtained from virgin olive oil have been tested for possible cytostatic activity against McCoy cells, using 6-mercaptopurine as a positive control. The samples of sterols and triterpenic dialcohols showed a strong activity.

To explore the utility of glycosyltransferases as novel biocatalysts, we isolated the glycosyltransferase genes CaUGT2 and SbUGTA1 from Catharanthus roseus and Starmerella bombicola, respectively and heterologously expressed them in Escherichia coli. The purified recombinant proteins were assayed with a variety of small molecule substrates. Carvacrol and its phenol isomer thymol are efficiently glucosylated by CaUGT2. The Vmax/Km ratios show that CaUGT2 exhibits the highest specificity towards carvacrol, followed by thymol, geraniol, eugenol, vanillin, menthol, and tyrosol. In contrast, SbUGTA1 accepts ω-hydroxy fatty acids and 1-alkanols as substrates. The Vmax/Km ratios indicate that SbUGTA1 exhibits the highest specificity towards 16-hydroxy palmitic acid, followed by octanol, decanol, and hexadecanol. In biotransformation experiments 23, 88 and 99% of octanol, 16-hydroxy palmitic acid, and decanol, respectively is converted into the corresponding β-glucosides by E. coli cells expressing SbUGTA1 whereas those cells expressing CaUGT2 glucosylate 18, 61, 77 and 97% of applied eugenol, thymol, vanillin, and carvacrol, respectively. To optimize the biotransformation rate, the effects of the concentration of IPTG, glucose, and substrate on the production of glucosides were tested. Taken together, this procedure is a simple operation, environmentally friendly, and is useful for the preparation of glycosides as additives for food and cosmetics.

The main causes of food spoilage come from the process of oxidation and the contamination by microorganisms. For the purpose of increasing food shelf-life the industries employ different techniques, being the addition of preservatives, one of the most used. The aim of this contribution was to investigate the potential antioxidant properties of tyrosol (4-hydroxyphenethyl alcohol, 4-OH) and tyrosol derived isomers (2-hydroxyphenethyl alcohol, 2-OH and 3-hydroxyphenethyl alcohol, 3-OH) against reactive oxygen species (ROS) and the antimicrobial effect on Staphylococcus aureus and Escherichia coli. Furthermore, the type of antioxidant effect of substrates and commercial antioxidants mixtures was studied. Upon visible-light, the substrates interacted with the vitamin B2 and different ROS were generated. All the compounds deactivated O₂(¹Δ_g) and O₂^●-, whereas only 2-OH and 3-OH inhibited H₂O₂ and HO^●. The substrates exhibited a synergistic antioxidant effect when combined with commercial antioxidants. 2-OH showed antimicrobial activity against strains tested.

Keywords: (±)-6-Hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox) (PubChem CID: 40634); 2-Hydroxyphenethyl alcohol (PubChem CID: 82200); 3-Hydroxyphenethyl alcohol (PubChem CID: 83404); 4-Hydroxyphenethyl alcohol (PubChem CID: 10393); Antimicrobials; Catalase from bovine liver (BRENDA: EC1.11.1.6); Phenolic antioxidants; Photodegradation; Reactive oxygen species; Riboflavin; Sodium azide (PubChem CID: 4427778); Sodium benzoate (PubChem CID: 517055); Superoxide dismutase (BRENDA: EC1.15.1.1); Vitamin B2; l-Ascorbic acid (PubChem CID: 54670067).

Candida lusitaniae is an emerging opportunistic yeast and an attractive model to discover new virulence factors in Candida species by reverse genetics. Our goal was to create a dpp3Δ knockout mutant and to characterize the effects of this gene inactivation on yeast in vitro and in vivo interaction with the host. The secretion of two signaling molecules in Candida species, phenethyl alcohol (PEA) and tyrosol, but not of farnesol was surprisingly altered in the dpp3Δ knockout mutant. NO and reactive oxygen species (ROS) production as well as tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) secretion were also modified in macrophages infected with this mutant. Interestingly, we found that the wild-type (WT) strain induced an increase in IL-10 secretion by zymosan-activated macrophages without the need for physical contact, whereas the dpp3Δ knockout mutant lost this ability. We further showed a striking role of PEA and tyrosol in this modulation. Last, the DPP3 gene was found to be an essential contributor to virulence in mice models, leading to an increase in TNF-α secretion and brain colonization. Although reinsertion of a WT DPP3 copy in the dpp3Δ knockout mutant was not sufficient to restore the WT phenotypes in vitro, it allowed a restoration of those observed in vivo. These data support the hypothesis that some of the phenotypes observed following DPP3 gene inactivation may be directly dependent on DPP3, while others may be the indirect consequence of another genetic modification that systematically arises when the DPP3 gene is inactivated.

We investigated the effects of tyrosol (Tyr) on anterior chamber paracentesis (ACP)-induced anterior uveitis in beagle dogs, as determined by protein and prostaglandin E2 (PGE2) concentrations in the aqueous humor (AH). Tyr at a dose of 100 or 200 mg/kg or 2.2 mg/kg of carprofen as a positive control was administered orally twice daily from 2.5 days before paracentesis. The initial ACP was performed in one eye of individual dogs and 0.5 ml AH was aspirated. The secondary AH was collected 60 min later. Pretreatment with 200 mg/kg of Tyr and carprofen significantly decreased aqueous protein and PGE2 concentrations compared to the control group. Overall, these findings suggested that Tyr was useful for the management of canine anterior uveitis.

Background: Calcium is a preservative and firming agent largely used in the table olive industry. Foliar applications of calcium (CaCl₂ ) before harvest have been proposed in other fruits to increase firmness and reduce physiological disorders or internal damage. However, there is still a shortage of information regarding the source, the concentration, the number and the period of calcium application onto the canopy to get an effective response of olive quality. In this study, we aimed to investigate the effect of two concentrations of CaCl₂ foliar treatments (0.5% and 1.0%), applied at different stages of fruit development (at the end of fruit set, end of pit hardening, and prior to harvesting) on olive quality for two varieties ('Manzanilla de Sevilla' and 'Ascolanta tenera'), cultivated in two different geographical areas (Spain and Italy, respectively).

Results: The applied Ca concentrations enhanced the fruit calcium content and decreased sodium and potassium. They also improved the mechanical properties without modifying fruit morphology, cuticle thickness nor causing phytotoxicity. Foliar treatments increased the oil content in the pulp (dry weight basis) and the amount of hydroxytyrosol, tyrosol and oleuropein, among other phenols.

Conclusion: Calcium foliar applications during fruit development effectively increase olive quality. This article is protected by copyright. All rights reserved.

Keywords: firmness; fruit damage; phenolic compounds; ‘Ascolana tenera’; ‘Manzanilla de Sevilla’.

Colletotrichum lupini is the causal agent of lupin (Lupinus albus L.) anthracnose, a destructive seed-borne disease affecting stems and pods. Despite that several biological studies have been carried out on this pathogen, the production of secondary metabolites has not yet been investigated. Thus, a strain of C. lupini, obtained from symptomatic stems of L. albus, has been grown in vitro to evaluate its ability to produce bioactive compounds. From its culture filtrates, a 3-substituted indolinone, named lupindolinone, and a 5,6-disubstituted tetrahydro-α-pyrone, named lupinlactone, were isolated together with the known (3R)-mevalonolactone and tyrosol. Lupindolinone and lupinlactone were characterized as 3-ethylindolin-2-one and 5-hydroxy-6-methyltetrahydropyran-2-one by spectroscopic methods (essentially nuclear magnetic resonance [NMR] and high-resolution electrospray ionization mass spectrometry [HR ESI-MS]). The R absolute configuration (AC) at C-5 of lupinlactone was determined by applying the modified Mosher's method. Thus, considering its relative stereochemistry assigned by NMR spectroscopy, the AC of lupinlactone could be formulated as 5R,6S. Lupindolinone was isolated as racemic mixture as shown by investigation using chiroptical methods. The metabolites were assayed in different biological tests and proved to have some activities at the used concentration.