Search

Oxidative stress and inflammation lead by dietary oxidised lipids, as oxysterols, have been linked to the loss of intestinal barrier integrity, a crucial event in the initiation and progression of intestinal disorders. In the last decade, probiotic lactobacilli have emerged as an interesting tool to improve intestinal health, thanks to their antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the ability of two commercial probiotic strains of lactobacilli (Lactiplantibacillus plantarum 299v® (DMS 9843) and Lacticaseibacillus casei DG® (CNCMI-1572)), both as live bacteria and intracellular content, to attenuate the oxysterols-induced alteration of intestinal epithelial Caco-2 cell monolayer permeability. Our investigation was focused on the modulation of tight junctions (TJs) proteins, occludin, ZO-1 and JAM-A, in relation to redox-sensitive MAPK p38 activation. Obtained results provided evidence on the ability of the two probiotics to counteract the alteration of monolayer permeability and loss of TJs proteins, at least in part, through the modulation of p38 pathway. The protective action was exerted by live bacteria, whose adhesion to Caco-2 cells was not altered by oxysterols, and bacterial intracellular components equally able to interact with the signaling pathway.

Aims: The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes, but dietary modification of the microbiota may promote glycaemic control. This study investigated whether differences in gut microbiota between control and diabetic mice influence the production of polyphenolic metabolites from wheat wholegrain (WW). Second, the study assessed whether changes in metabolite profiles affect pancreatic beta cell function. Methods: Faecal samples (1% (v/v)) from control or high‐fat high‐fructose fed (HFHF) mice were fermented in vitro with 0.1% (w/v) WW for 0, 6 and 24 h. Polyphenolic profiles were determined by UHPLC‐MS/MS and microbiota composition by bacterial 16S rRNA sequencing and qPCR. MIN6 beta cell apoptosis was assessed by measurement of caspase activity and insulin release by radioimmunoassay. Results: Levels of WW polyphenols were decreased in fermentation samples from HFHF with time and HFHF showed an overall dysbiotic microbiome profile (p 0.05, n=3). Insulin secretion was inhibited at 0 h by control, but not HFHF supernatant, and this effect was partly reverted at 24 h (p < 0.05, n=5). Conclusion: Our results suggest that a dysbiotic HFHF microbiota profile affects the production of polyphenolic metabolites with potential implications for beta cell function.

Online pornography, like other forms of cultural production, is increasingly subject to processes of platformization. While research has focused on the diffusion of online pornography and its broader implications, less attention has been paid to the algorithmic infrastructures through which platforms distribute and manage pornographic content, and how this might reiterate socially embedded views and perspectives. To fill this gap, we consider how Pornhub, currently the leading porn platform, establishes the gender identity of its users, and how this affects the structure of the platform and the distribution and recommendation of content within it. We collected data about 1.600 variations of Pornhub’s homepages, as well as data about 25.000 videos suggested to 10 accounts with differing self-declared gender identities. Through this data and an analysis of the signup procedure, we underline how Pornhub segments, distributes, and manages content based on the profiling of its users, increasingly following the logics of the platformization of content. Findings point to how Pornhub’s algorithmic suggestions and the structure of the platform concur to reiterate a heteronormative perspective on sexual desire, sexuality, and gender identities.

Wholegrain oats contain a variety of phenolic compounds thought to help maintain healthy vascular function, through the maintenance of local levels of the vasodilator nitric oxide (NO). Thus, the full molecular mechanisms involved are not yet clear. With this work we aim to understand the possible cellular mechanisms by which avenanthramides and ferulic acid derivatives, present in oats, may help maintain a healthy vascular function through the modulation of the NO pathway. Primary Human Umbilical Vein Endothelial Cells (HUVEC) were exposed to ferulic acid, isoferulic acid, hydroferulic acid, ferulic acid 4-O-glucuronide, isoferulic acid 3-O-sulfate, dihydroferulic acid 4-O-glucuronide, avenanthramide A, avenanthramide B and avenanthramide C (1 μM) or vehicle (methanol) for 24 h. Apocynin and Nω-Nitro-L-arginine (L-NNA) were additionally included as controls. NO and cyclic GMP (cGMP) levels, superoxide production and the activation of the Akt1/eNOS pathway were assessed. The statistical analysis was performed using one-way ANOVA followed by a Tukey post-hoc t-test. Apocynin and all phenolic compounds increased NO levels in HUVEC cells (increased DAF2-DA fluorescence and cGMP), and significantly reduced superoxide levels. Protein expression results highlighted an increase in the Akt1 activation state, and increased eNOS expression. Overall, our results indicated that the glucuronide metabolites do not enhance NO production through the Akt1/eNOS pathway, thus all compounds tested are able to reduce NO degradation through reduced superoxide formation.

Background Dietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this pilot study was to determine the concentration of the main dietary lignans in an oilseed mix, and explore the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women’s faecal samples. The lignan content and enterolignan production were measured by ultra‐high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS), and the faecal-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing. Results In vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp. Conclusions Despite the small sample size, our pilot study revealed that lignan-rich oilseeds could strongly influence the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. Further studies in larger cohorts are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to meet the cellular needs of endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors into enterolignans.

Algorithmic personalization is difficult to approach because it entails studying many different user experiences, with a lot of variables outside of our control. Two common biases are frequent in experiments: relying on corporate service API and using synthetic profiles with small regards of regional and individualized profiling and personalization. In this work, we present the result of the first crowdsourced data collections of YouTube’s recommended videos via YouTube Tracking Exposed (YTTREX). Our tool collects evidence of algorithmic personalization via an HTML parser, anonymizing the users. In our experiment we used a BBC video about COVID-19, taking into account 5 regional BBC channels in 5 different languages and we saved the recommended videos that were shown during each session. Each user watched the first five second of the videos, while the extension captured the recommended videos. We took into account the top20 recommended videos for each completed session, looking for evidence of algorithmic personalization. Our results showed that the vast majority of videos were recommended only once in our experiment. Moreover, we collected evidence that there is a significant difference between the videos we could retrieve using the official API and what we collected with our extension. These findings show that filter bubbles exist and that they need to be investigated with a crowdsourced approach.

BackgroundDietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this study was to determine the concentration of the main dietary lignans in an oilseed mix, and evaluate the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women’s faecal samples. The lignan content and enterolignan production were measured by ultra‐high-performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS), and the gut-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing.ResultsIn vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp. ConclusionsDespite the small sample size, our results revealed that lignan-rich oilseeds have a strong influence on the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. More studies are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to satisfy cellular needs for endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors to enterolignans.

Highlights • Commercial oat products contained ten phenolic acids and three avenanthramides. • Commercial oats provide 15.79–25.05 mg total phenolic acids in a 40 g serving of oats. • The concentrations and compositions in the products were broadly similar. • Major component was ferulic acid (58–78.1%) in all products. • Oatbran concentrate has the highest levels of phenolic acids and avenanthramides., Oats contain a range of phenolic acids and avenanthramides which may have health benefits. Analysis of 22 commercial oat products (oat bran concentrate, oat bran, flaked oats, rolled oats and oatcakes) using HPLC-DAD detected eleven bound and thirteen free + conjugated phenolic acids and avenanthramides. The oat products (excluding concentrate) provided between 15.79 and 25.05 mg total phenolic acids (9.9–19.33 mg bound, 4.96–5.72 mg free + conjugated) and between 1.1 and 2 mg of avenanthramides in a 40 g portion while an 11 g portion of oat concentrate provided 16.7 mg of total phenolic acids (15.17 mg bound, 1.53 mg free + conjugated) and 1.2 mg of avenanthramides. The compositions and concentrations of the components in the different products were broadly similar, with the major component being ferulic acid (58–78.1%). The results show that commercial oat products are a source of phenolic acids and avenanthramides for consumers.

Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular function; however, data relating to effects in the postprandial state are limited. The present study investigated the postprandial, time-dependent (0–7 h) impact of citrus flavanone intake on vascular function. An acute, randomised, controlled, double-masked, cross-over intervention study was conducted by including middle-aged healthy men (30–65 years, n 28) to assess the impact of flavanone intake (orange juice: 128·9 mg; flavanone-rich orange juice: 272·1 mg; homogenised whole orange: 452·8 mg; isoenergetic control: 0 mg flavanones) on postprandial (double meal delivering a total of 81 g of fat) endothelial function. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at 0, 2, 5 and 7 h. Plasma levels of naringenin/hesperetin metabolites (sulphates and glucuronides) and nitric oxide species were also measured. All flavanone interventions were effective at attenuating transient impairments in FMD induced by the double meal (7 h post intake; P

OBJECTIVES: Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan. However, oats contain an array of phenolics, including ferulic acid and avenanthramides, which may also contribute to the cardiovascular health benefits. We investigated whether daily consumption of oat phenolics leads to improvement of markers of CVDrisks in adults. METHODS: In a 3 arm crossover double-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (68.1 mg of phenolics); 2) oatbran concentrate + rice porridge/wheat cracker (38.9 mg of phenolics) or 3) rice porridge/wheat cracker (13.8 mg of phenolic acids) for 4 weeks. All treatments were matched in macro nutrients, energy (500 kcal) and total soluble fiber (4.8 g). The primary endpoint was flow mediated dilatation (FMD) and other cardiovascular endpoints were laser doppler imaging, 24 h blood pressure and LDL/HDL cholesterol. RESULTS: Consumption of high phenolic oats led to a significant improvement in 24-hour SBP (−1.16 mm Hg), night time SBP (−5.1 mm Hg) and night time DBP (−2.3 mm Hg) (P

At intestinal level, after acute or chronic exposure to iNOS-derived NO, a toxic mechanism of action leads to inflammation and degenerative diseases. The aim of this study was to investigate the effect of glucuronide and sulfate metabolites of the extra virgin olive oil phenols tyrosol (Tyr) and hydroxytyrosol (HT), in comparison with their parent compounds, on the release of NO following exposure to a pro-inflammatory stimulus, the bacterial lipopolysaccharide (LPS). Human colon adenocarcinoma cells (Caco-2), differentiated as normal enterocytes, were treated with pathological concentrations of LPS, in order to stimulate iNOS pathway, which involves NF-ĸB activation through IĸBα phosphorylation and subsequent degradation induced by Akt or MAPKs. All the tested metabolites inhibited NO release induced by LPS, acting as inhibitors of iNOS expression, with an efficacy comparable to that of the parent compounds. HT and Tyr metabolites were effective in the inhibition of IĸBα degradation. No one of the compounds was able to inhibit Akt activation, whereas they modulated p38 and ERK1/2 MAPK. Obtained data show that HT and Tyr metabolites are able to prevent a pathological NO overproduction at intestinal level, where they concentrate, thus significantly contributing to the protective activity exerted by their parent compounds against inflammation.

Brown seaweeds such asAscophyllum nodosumare a rich source of phlorotannins (oligomers and polymers of phloroglucinol units), a class of polyphenols that are unique to Phaeophyceae. At present, there is no information on the bioavailability of seaweed polyphenols and limited evidence on their bioactivityin vivo. Consequently, we investigated the gastrointestinal modificationsin vitroof seaweed phlorotannins fromA. nodosumand their bioavailability and effect on inflammatory markers in healthy participants.In vitro, some phlorotannin oligomers were identified after digestion and colonic fermentation. In addition, seven metabolites corresponding toin vitro-absorbed metabolites were identified. Urine and plasma samples contained a variety of metabolites attributed to both unconjugated and conjugated metabolites (glucuronides and/or sulphates). In both urine and plasma, the majority of the metabolites were found in samples collected at late time points (6–24 h), suggesting colonic metabolism of high-molecular-weight phlorotannins, with three phlorotannin oligomers (hydroxytrifuhalol A, 7-hydroxyeckol, C-O-C dimer of phloroglucinol) identified in urine samples. A significant increase of the cytokine IL-8 was also observed. Our study shows for the first time that seaweed phlorotannins are metabolised and absorbed, predominantly in the large intestine, and there is a large inter-individual variation in their metabolic profile. Three phlorotannin oligomers present in the capsule are excreted in urine. Our study is the first investigation of the metabolism and bioavailability of seaweed phlorotannins and the role of colonic biotransformation. In addition, IL-8 is a possible target for phlorotannin bioactivity.

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

Dietary habits have been strongly linked to the maintenance of intestinal epithelium homeostasis, whose alteration may contribute to the pathogenesis of inflammatory diseases and cancer. Polyphenols are among those dietary components suggested to be beneficial for gut health. Within a balanced Mediterranean type diet, a good portion of ingested polyphenols comes from olives and extra virgin olive oil (EVOO). Most of them reach the intestine, where they may be directly absorbed or metabolized under absorption. Others undergo an extensive gastrointestinal biotransformation, producing various metabolites that retain the potential beneficial effect of the parent compounds, or exert a more efficient biological action themselves. Ingested EVOO polyphenols (EVOOP) and their metabolites will be particularly concentrated in the intestinal lumen, where they might exert a significant local action. In this review we summarize the few studies that investigated the effect of EVOOP at the intestinal level, focusing on the possible mechanism of action in relation to their interaction with the microbiota, and their ability to potentially modulate the oxidative status of the intestinal epithelial layer, inflammation and immune response.

Background\ud Epidemiologic evidence suggests that a diet rich in (poly)phenols has beneficial effects on many chronic diseases. Brown seaweed is a rich source of (poly)phenols.\ud \ud Objective\ud The aim of this study was to investigate the bioavailability and effect of a brown seaweed (Ascophyllum nodosum) (poly)phenol extract on DNA damage, oxidative stress, and inflammation in vivo.\ud \ud Design\ud A randomized, double-blind, placebo-controlled crossover trial was conducted in 80 participants aged 30–65 y with a body mass index (in kg/m2) ≥25. The participants consumed either a 400-mg capsule containing 100 mg seaweed (poly)phenol and 300 mg maltodextrin or a 400-mg maltodextrin placebo control capsule daily for an 8-wk period. Bioactivity was assessed with a panel of blood-based markers including lymphocyte DNA damage, plasma oxidant capacity, C-reactive protein (CRP), and inflammatory cytokines. To explore the bioavailability of seaweed phenolics, an untargeted metabolomics analysis of urine and plasma samples after seaweed consumption was determined by ultra-high-performance liquid chromatography–high-resolution mass spectrometry.\ud \ud Results\ud Consumption of the seaweed (poly)phenols resulted in a modest decrease in DNA damage but only in a subset of the total population who were obese. There were no significant changes in CRP, antioxidant status, or inflammatory cytokines. We identified phlorotannin metabolites that are considered potential biomarkers of seaweed consumption including pyrogallol/phloroglucinol-sulfate, hydroxytrifurahol A-glucuronide, dioxinodehydroeckol-glucuronide, diphlorethol sulfates, C-O-C dimer of phloroglucinol sulfate, and C-O-C dimer of phloroglucinol.\ud \ud Conclusions\ud To the best of our knowledge, this work represents the first comprehensive study investigating the bioactivity and bioavailability of seaweed (poly)phenolics in human participants. We identified several potential biomarkers of seaweed consumption. Intriguingly, the modest improvements in DNA damage were observed only in the obese subset of the total population. The subgroup analysis should be considered exploratory because it was not preplanned; therefore, it was not powered adequately. Elucidation of the biology underpinning this observation will require participant stratification according to weight in future studies. This trial was registered at clinicaltrials.gov as NCT02295878.

Epidemiological evidence suggests an inverse correlation between wine consumption and the incidence of cardiovas- cular and neurodegenerative disorders. Although white wines are generally low in polyphenol content as compared to red wines, Champagne wine has been shown to contain relatively high amounts of phenolic acids that may exert protective cellular actions in vivo. Recent evidence suggest that Champagne phenolic acids may express their beneficial properties through their interaction with cellular signaling pathways and related machinery that mediate cell function under both normal and pathological condi- tions. In this review we aim to provide an overview of the role that Champagne consumption plays in maintaining cardiovascular health and cognitive function. We discuss epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and we consider how their biological mechanisms at the cellular level may underpin their physiological effects. Together, these data indicate that polyphenols present in Champagne may hold cardioprotective and neuroprotective potential in delaying the onset of degenerative disorders.

While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls.In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation.Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression.Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex.

Polyphenols have been reported to exert neuroprotective actions through the potential to protect neurons against neurotoxin-induced injury, neuroinflammation, and the potential to promote memory, learning and cognitive performances. Despite significant advances in our understanding of the biology of polyphenols, the exact molecular and cellular mechanisms underlying their biological effects are currently unclear. While historically polyphenols were regarded as powerful antioxidants, recent data suggest they do not act as conventional hydrogen-donating molecules in vivo, but rather exert modulatory actions in cells through the modulation of signalling pathways. Together, these processes act to maintain brain homeostasis and play important roles in neuronal stress adaptation and thus polyphenols have the ability to prevent the progression of neurodegenerative pathologies. This chapter will describe the potential of polyphenols to modulate brain functions and will summarise the latest information regarding the possible mechanisms implicated in such beneficial effects.

Oxidative stress is associated with the pathology of neurodegenerative diseases. Identification of small molecules capable of protecting against oxidative stress is therefore of significant importance. In this context, a library of 76 hydroxy flavones, methoxy flavones and their 4-thio analogues has been evaluated for neuroprotection against H2O2-induced oxidative stress. This revealed the synthetic 7,8-dihydroxy 4-thioflavones as neuroprotective compounds, with 14d and 18d showing highest neuroprotective effects at lower concentrations (0.3 μM). Neuroprotection was found to be mediated via activation of the anti-apoptotic cell survival proteins of the ERK1/2 and PI3K/Akt pathways. Structure-activity relationship analysis revealed the B-ring phenyl group as essential for greater neuroprotection. Replacing the 4-C=O moiety with a 4-C=S moiety also generally enhanced neuroprotection.

The moderate consumption of red wine has been proposed to reduce the incidence of colorectal cancer. Its anti-cancer action my in part be mediated by the actions of polyphenols on colon cancer epithelial cells. We show that a red wine phenolic (50 μg/ml) extract devoid of anthocyanins (removed to reflect polyphenol bioavailability to the large intestine) and the major red wine flavonols quercetin, myricetin, laricitrin and syringetin (50 μM) are capable of inhibiting the proliferation of colorectal epithelial adenocarcinoma cells. This anti-proliferative activity was partly mediated by the direct cytotoxic actions of flavonols and also their ability to cause a significant cell cycle blockage in G2/M. The anti-proliferative effects induced by flavonols were preceded, in most cases, by a strong and significant reduction of cyclooxygenase-2 (COX-2) and cyclin D1 expression. These results indicate that the observed inverse correlation between colon cancer and a moderate red wine intake may be partly mediated by the actions of red wine flavonols on the growth of cancer cells.

There is significant interest in the beneficial health properties of anthocyanins/anthocyanidins. Future investigations into their physiological effects will require human intervention with precise amounts of anthocyanins/anthocyanidins. We have investigated the total anthocyanin/anthocyanidin content of common berry fruits and designed an intervention diet intended to deliver a balanced profile of different anthocyanidins. Using acid hydrolysis and HPLC-diode array analysis we report the individual profile and total anthocyanidin profile/content of blueberry (148.76 mg/100 g FW), blackberry (76.78 mg/100 g FW), cranberry (19.30 mg/100 g FW), black grape (28.09 mg/100 g FW), raspberry (104.38 mg/100 g FW) and strawberry (41.09 mg/100 g FW). The measured anthocyanidin content in the various fruits was used to design an intervention diet (15 g of blueberry, 5 g of blackberry, 30 g cranberry, 20 g of grape, 5 g of raspberry and 25 g of strawberry; 100 g mixed fruit portion) capable of delivering high amounts of the six main anthocyanidins.

Polyphenols are found ubiquitously in plants and their regular consumption has been associated with a reduced risk of a number of chronic diseases, including cancer, cardiovascular disease (CVD) and neurodegenerative disorders. Rather than exerting direct antioxidant effects, the mechanisms by which polyphenols express these beneficial properties appear to involve their interaction with cellular signaling pathways and related machinery that mediate cell function under both normal and pathological conditions. We illustrate that their interactions with two such pathways, the MAP kinase (ERK, JNK, p38) and PI3 kinase/Akt signaling cascades, allow them to impact upon normal and abnormal cell function, thus influencing the cellular processes involved in the initiation and progression of cancer, CVD and neurodegeneration. For example, their ability to activate ERK in neurons leads to a promotion of neuronal survival and cognitive enhancements, both of which influence the progression of Alzheimer’s disease, whilst ERK activation by polyphenols in vascular endothelial cells influences nitric oxide production, blood pressure and ultimately CVD risk. The main focus of this review is to provide an overview of the role that polyphenols play in the prevention of cancer, cardiovascular disease and neurodegeneration. We present epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and in each case we consider how their actions at the cellular level may underpin their physiological effects.

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

Evidence suggests that a combination of oxidative stress, neuroinflammation and the formation of endogenous neurotoxins contribute to the underlying neuronal death associated with neurodegenerative diseases. In this study we have investigated the ability of the berry-derived flavonoids to protect against neuronal damage induced by neuroinflammation and the neurotoxin 5-S-cysteinyl-dopamine. The flavanols (+)-catechin and (-)-epicatechin, but not the anthocyanidin pelargonidin, were observed to attenuate LPS/IFN-?-induced TNF-a production in glial cells and associated neuronal injury. In contrast, pre-treatment of primary cortical neurons with pelargonidin, (+)-catechin and (-)-epicatechin (0.1 and 0.3 µM) resulted in concentration-dependant protection against 5-S-cysteinyl-dopamine-induced neurotoxicity. Together these data suggest that berry-derived flavonoids may offer some protection against the neuronal injury relevant to the aetiology of the Parkinson’s and Alzheimer’s diseases.

Extra virgin olive oil is rich in phenolic compounds which are believed to exert beneficial effects against many pathological processes, including the development of colon cancer. We show that one of the major polyphenolic constituents of extra virgin olive oil, hydroxytyrosol (HT), exerts strong antiproliferative effects against human colon adenocarcinoma cells via its ability to induce a cell cycle block in G2/M. These antiproliferative effects were preceded by a strong inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation and a downstream reduction of cyclin D1 expression, rather than by inhibition of p38 activity and cyclooxygenase-2 (COX-2) expression. These findings are of particular relevance due to the high colonic concentration of HT compared to the other olive oil polyphenols and may help explain the inverse link between colon cancer and olive oil consumption.

Olive oil, a typical ingredient of the Mediterranean diet, possesses many beneficial health effects. The biological activities ascribed to olive oil consumption are associated in part to its phenolics constituents, and mainly linked to the direct or indirect antioxidant activity of olive oil phenolics and their metabolites, which are exerted more efficiently in the gastrointestinal (GI) tract, where dietary phenolics are more concentrated when compared to other organs. In this regard, we present a brief overview of the metabolism, biological activities, and anticancer properties of olive oil phenolics in the GI tract.

Bioavailability studies in animals and humans fed with extravirgin olive oil demonstrated that hydroxytyrosol and tyrosol, the major simple phenolic compounds in extravirgin olive oil, are dose-dependently absorbed and excreted. Once absorbed, they undergo extensive metabolism; hydroxytyrosol and tyrosol concentrate mainly in the kidney, where they may exert an important role in the prevention of oxidative stress induced renal dysfunction. In this study we monitored the ability of hydroxytyrosol and tyrosol to protect renal cells (LLC-PK1) following oxidative damage induced by H2O2. Oxidative stress was evaluated by monitoring the changes of the membrane lipid fraction. Hydroxytyrosol exerted a significant antioxidant action, inhibiting the production of MDA, fatty acids hydroperoxides and 7-ketocholesterol, major oxidation products of unsaturated fatty acids and cholesterol, and thus protecting the cells from H2O2-induced damage. Tyrosol, instead, in this experimental model, did not exert any protective effect.

Myrtle (Myrtus communis L.), a culinary spice and flavouring agent for alcoholic beverages widespread in the Mediterranean area and especially in Sardinia, contains the structurally unique oligomeric non-prenylated acylphloroglucinols, semimyrtucommulone and myrtucommulone A, whose antioxidant activity was investigated during the oxidative modification of lipid molecules implicated in the onset of cardiovascular diseases. Both acylphloroglucinols showed powerful antioxidant properties during the thermal (140 degrees C), solvent-free degradation of cholesterol. Moreover, the pre-treatment with semimyrtucommulone and myrtucommulone A significantly preserved LDL from oxidative damage induced by Cu(2+) ions at 2h of oxidation, and showed remarkable protective effect on the reduction of polyunsaturated fatty acids and cholesterol, inhibiting the increase of their oxidative products (conjugated dienes fatty acids hydroperoxides, 7beta-hydroxycholesterol, and 7-ketocholesterol). Taking into account the widespread culinary use of myrtle leaves, the results of the present work qualify the natural compounds semimyrtucommulone and myrtucommulone A as interesting dietary antioxidants with potential antiatherogenicity.

This study investigated the effect of synthetic capsiate, a simplified analogue of capsiate, and vanillyl alcohol on the oxidative stress induced by tert-butyl hydroperoxide (TBH) in a line of fibroblasts derived from monkey kidney (Vero cells). In response to the TBH-mediated oxidative stress, a reduction of the levels of total unsaturated fatty acids and cholesterol was observed, and a rise in the concentrations of conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with both synthetic capsiate and vanillyl alcohol preserved Vero cells from oxidative damage and showed a remarkable protective effect on the reduction of the levels of total unsaturated fatty acids and cholesterol, inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides, and 7-ketocholesterol. Both compounds were effective against peroxidation of cell membrane lipids induced by TBH, with synthetic capsiate essentially acting as a pro-drug of vanillyl alcohol, its hydrophilic hydrolytic derivative.

Epidemiological evidences suggest an inverse correlation between wine consumption and the incidence of neurodegenerative disorders. Although wine is a complex matrix, such benefit is believed to be in large part attributable to the intake of specific polyphenols present in great quantity in wine. Red wines contain between 900 and 1400 mg/L of polyphenols; meanwhile white wines are generally lower in polyphenol content (50–300 mg/L). Nevertheless, Champagne wine has been shown to contain relatively high amounts of phenolic acids that may exert protective cellular actions in vivo. Recent evidences suggest that both red wine and Champagne polyphenols may express their beneficial properties through their interaction with cellular signalling pathways and related machinery that mediate cell function under both normal and pathological conditions. The use of grape-derived phenolic extracts and pure phenolic compounds constitutes a good approach to study the effects of wine consumption in neuroprotection. In this chapter, we aim to provide an overview of the role that wine consumption plays in maintaining cognitive function. We discuss epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and we consider how their biological mechanisms at the cellular level may underpin their physiological effects. Together, these data indicate that polyphenols present in wine may hold neuroprotective potential in delaying the onset of degenerative disorders.

White wines are generally low in polyphenol content as compared to red wines. However, Champagne wines have been shown to contain relatively high amounts of phenolic acids that may exert protective cellular actions in vivo. In this study, we have investigated the potential neuroprotective effects of Champagne wine extracts, and individual phenolics present in these extracts, against peroxynitrite-induced injury. Organic and aqueous Champagne wine extracts exhibited potent neuroprotective activity against peroxynitrite-induced injury at low concentrations (0.1 microg/mL). This protection appeared to be in part due to the cellular actions of individual components found in the organic extracts, notably tyrosol, caffeic acid, and gallic acid. These phenolics were observed to exert potent neuroprotection at concentrations between 0.1 and 10 microM. Together, these data suggest that polyphenols present in Champagne wine may induce a neuroprotective effect against oxidative neuronal injury.

We have conducted a detailed investigation into the absorption, metabolism and microflora-dependent transformation of hydroxytyrosol (HT), tyrosol (TYR) and their conjugated forms, such as oleuropein (OL). Conjugated forms underwent rapid hydrolysis under gastric conditions, resulting in significant increases in the amount of free HT and TYR entering the small intestine. Both HT and TYR transferred across human Caco-2 cell monolayers and rat segments of jejunum and ileum and were subject to classic phase I/II biotransformation. The major metabolites identified were an O-methylated derivative of HT, glucuronides of HT and TYR and a novel glutathionylated conjugate of HT. In contrast, there was no absorption of OL in either model. However, OL was rapidly degraded by the colonic microflora resulting in the formation of HT. Our study provides additional information regarding the breakdown of complex olive oil polyphenols in the GI tract, in particular the stomach and the large intestine.

The antioxidant activity of various extracts (MeOH, petroleum ether, EtOAc) from the aerial parts of Psoralea morisiana, an endemic Sardinian plant, was evaluated during autoxidation and iron-mediated oxidation of linoleic acid at 37 °C and during cholesterol oxidation at 140 °C, in the absence of solvent. The activity of erybraedin C, bitucarpin A and plicatin B, isolated from the extracts, was investigated under the same experimental conditions and compared to that of BHT and α-tocopherol. All the extracts, erybraedin C (major constituent of the extracts) and plicatin B showed powerful antioxidant properties. None of the extracts and pure compounds showed any prooxidant activity. The cytotoxicity of the extracts, erybraedin C, and plicatin B was further evaluated in VERO cells, a line of fibroblasts derived from monkey kidney. Erybraedin C, at non-cytotoxic concentrations, showed a strong inhibition of FeCl3-induced oxidation in VERO cells.

The activity of a single IP administration (15 or 30 mg/Kg body weight) of vanillyl nonanoate, a simplified analog of capsiate, on ferric nitrilotriacetate (Fe-NTA)-mediated oxidative damage was investigated. A sub-lethal dose of Fe-NTA (15 mg Fe/Kg body weight) was administered IP to rats; animals were sacrificed, and kidney and plasma were collected 1 h after injection. In response to the Fe-NTA administration, a reduction of the levels of total lipids, total unsaturated fatty acids and cholesterol was observed, accompanied by a rise in the concentrations of malondialdehyde (MDA), conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol in plasma and kidney 1 h after administration. A pre-treatment with synthetic capsiate (SCPT) showed remarkable protective effect on the reduction of the levels of total lipids, total unsaturated fatty acids and cholesterol, and the cellular antioxidant vitamin E, inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol in the plasma and kidney. The protective effect of SCPT and two analogues (vanillyl alcohol and vanillin) during the linoleic acid and cholesterol oxidation was investigated in in vitro systems, providing evidence of definite structure-activity relationships.

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

cope : Unlike other classes of polyphenols, there is a lack of knowledge regarding brown seaweed phlorotannins and their bioactivity. We investigated the impact of in vitro gastrointestinal digestion and colonic fermentation on the bioactivity of a seaweed phlorotannin extract from Ascophyllum nodosum and its high molecular weight (HMW) and low molecular weight (LMW) fractions. Methods and Results : The highest phlorotannin and total polyphenol (TP) concentration was observed in the HMW fraction. Antioxidant capacity broadly followed phlorotannin and TP levels, with HMW having the highest activity. Both gastrointestinal digestion (GID) and colonic fermentation (CF) significantly affected phlorotannin and TP levels, and antioxidant capacity of the extract and fractions. Despite this, in HT-29 cells, all GID extracts significantly inhibit cell growth, whereas CF extracts effectively counteracted H2O2 induced DNA damage. Conclusion : Although phlorotannins, TP levels and antioxidant power of the extracts were strongly reduced after in vitro digestion and fermentation, their anti-genotoxic activity and cell growth inhibitory effect in colon HT-29 cells was maintained and enhanced. HMW was the most effective fraction, indicating that the high molecular weight phlorotannins potentially exert a stronger beneficial effect in the colon. This article is protected by copyright. All rights reserved

The endogenous neurotoxin 5-S-cysteinyl-dopamine (CysDA) has been linked to the degeneration of dopaminergic neurons in the Substantia nigra. Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables that has been proposed as a potential chemopreventive agent, although its effects on other cells are less clear. This study was undertaken to investigate the protective effects of SFN against CysDA-induced injury in primary cortical neurons. The results indicate that SFN protects primary cortical neurons against CysDA-induced injury by a mechanism involving the increased nuclear translocation of Nrf2 and the increased activity of phase II enzymes such as glutathione-S-transferase, glutathione reductase, and thioredoxine reductase. Moreover, the protection exerted by SFN appears to be mediated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Akt/protein kinase B (PKB) pathways.