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Leaves of Vitis vinifera cv. Greco di Tufo, a precious waste made in the Campania Region (Italy), after vintage harvest, underwent reduction, lyophilization, and ultrasound-assisted maceration in ethanol. The alcoholic extract, as evidenced by a preliminary UHPLC-HR-MS analysis, showed a high metabolic complexity. Thus, the extract was fractionated, obtaining, among others, a fraction enriched in flavonol glycosides and glycuronides. Myricetin, quercetin, kaempferol, and isorhamnetin derivatives were tentatively identified based on their relative retention time and TOF-MS 2 data. As the localization of saccharidic moiety in glycuronide compounds proved to be difficult due to the lack of well-established fragmentation pattern and/or the absence of characteristic key fragments, to obtain useful MS information and to eliminate matrix effect redundancies, the isolation of the most abundant extract's compound was achieved. HR-MS/MS spectra of the compound, quercetin-3- O -glucuronide, allowed us to thoroughly rationalize its fragmentation pattern, and to unravel the main differences between MS/MS behavior of flavonol glycosides and glycuronides. Furthermore, cytotoxicity assessment on the (poly)phenol rich fraction and the pure isolated compound was carried out using central nervous system cell lines. The chemoprotective effect of both the (poly)phenol fraction and quercetin-3- O -glucuronide was evaluated., Competing Interests: The authors declare no conflicts of interest.

A series of chemical and biochemical parameters of edible hemp resources (seeds, oil, and flour) from the monoecious EU registered hemp genotype Fedora, was determined, including fatty acid profile, phytosterol composition, total phenolics, antioxidant activity, macro- and micro-elements. The fatty acid ω-3/ω-6 approached the nutritionally optimal 3/1 ratio. β-sitosterol and other phytosterols sterols dominated the unsaponifiable fraction. Hemp seeds, flour, and oil contained 767 ± 41, 744 ± 29, and 21 ± 5 mg GAE kg -1 total polyphenols, respectively. The antioxidant potential of Fedora flour and seeds, evaluated through the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay, was higher than that of oil. K and Mg were the most abundant macro-elements, particularly in flour, while the concentration of trace elements was Fe > Cu > Ni > Mn. The presence of an array of bioactive compound candidate Fedora products as health-promoting food matrices. The ATR-FTIR spectra of hemp-derived products indicated the proximate composition of macro-nutrients.

In this study, a hydroalcoholic chestnut shell extract was characterized and tested on six different human cell lines. Gallic, ellagic, and syringic acids were the most abundant non-condensed compounds in the chestnut extract, as determined by high performance liquid chromatography (HPLC). Tannins were mainly represented by condensed monomeric units of epigallocatechin and catechin/epicatechin. After 48 h of treatment, only the human hepatoblastoma HepG2 cells reached an inhibition corresponding to IC 50 with an increase of apoptosis and mitochondrial depolarization. The cytokinome evaluation before and after treatment revealed that the vascular endothelial growth factor (VEGF) and the tumor necrosis factor (TNF)-α decreased after the treatment, suggesting a potential anti-angiogenic and anti-inflammatory effect of this extract. Moreover, the metabolome evaluation by ¹H-NMR evidenced that the polyphenols extracted from chestnut shell (PECS) treatment affected the levels of some amino acids and other metabolites. Overall, these data highlight the effects of biomolecules on cell proliferation, apoptosis, cell cycle and mitochondrial depolarization, and on cytokinomics and metabolomics profiles.

Chewing gums may be particularly effective means for delivering and maintaining bioactive molecules, included in the gum formulation, able to have an anti-cariogenic effect. The purposes of this study were: to develop novel chewing gums containing quercetin (Qt); to evaluate their release using in vivo trial; finally, to test their in vivo antibacterial effect against oral Streptococcus mutans strains. A preliminary study was performed to produce new gums, enriched with the polyphenol quercetin. Then, a first in vivo experimental study was assessed to test the percentages of Qt released in the saliva of young volunteers. Moreover, a second clinical trial was performed to analyze the antibacterial capability of these enriched chewing gums against S. mutans strains after 14 days of daily consumption. The release analysis showed that a more effective release of Qt occurs in the first minutes of chewing, and it does not change saliva pH values. Moreover, Qt included in gums demonstrates an effective antibacterial activity, showing a reduction of the concentration of S. mutans strains in saliva samples, especially after 7 days. Qt included in experimental chewing gums could be efficiently released into the oral cavity and could promote an effective anti-caries concentration in volunteer's saliva, without changing salivary pH values.

Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract.

In this work, we characterized conjugated linolenic acids (e.g., punicic acid) as the major components of the hydrophilic fraction (80% aqueous methanol extract) from pomegranate (Punica granatum L.) seed oil (PSO) and evaluated their anti-inflammatory potential on some human colon (HT29 and HCT116), liver (HepG2 and Huh7), breast (MCF-7 and MDA-MB-231) and prostate (DU145) cancer lines. Our results demonstrated that punicic acid and its congeners induce a significant decrease of cell viability for two breast cell lines with a related increase of the cell cycle G0/G1 phase respect to untreated cells. Moreover, the evaluation of a great panel of cytokines expressed by MCF-7 and MDA-MB-231 cells showed that the levels of VEGF and nine pro-inflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IP-10, MIP-1α, MIP-1β, MCP-1 and TNF-α) decreased in a dose dependent way with increasing amounts of the hydrophilic extracts of PSO, supporting the evidence of an anti-inflammatory effect. Taken together, the data herein suggest a potential synergistic cytotoxic, anti-inflammatory and anti-oxidant role of the polar compounds from PSO.

The need to explore new alternative therapeutic strategies and chemoprevention methods for hepatocellular carcinoma is growing significantly. Selenium is a trace element that plays a critical role in physiological processes, and is used in cancer chemoprevention. The aim of this work was to test in vitro the effect of sodium selenite on the human hepatoma cell lines, HepG2 and Huh7, to assess its effect on the expression of GPX1, SELK and SELENBP1 and also to evaluate its action on inflammation determinants such as cytokines. Our results show that: (i) the increase observed for the GPX1 and SELK expression is correlated with an increase in the sodium selenite concentration, also evidencing an inverse association between the levels of these two proteins and SELENBP1; (ii) the selenium concentrations evaluated in protein extracts increase in proportional way with the selenite concentrations used in the treatment, suggesting that other selenoproteins can also be modulated and should be evaluated in further studies, and (iii) some cytokines, VEGF and three pro-inflammatory cytokines, i.e., IL-6, IL-8, and IL-17, decreased with an increasing selenite concentration. Finally, interactomic studies show that GPX1 and SELK, and the four pro-inflammatory cytokines are functionally correlated evidencing a putative anti-inflammatory role for the selenite.