Cooking, Digestion, and In Vitro Colonic Fermentation of Nigerian Wholegrains Affect Phenolic Acid Metabolism and Gut Microbiota Composition.

Wholegrains contain both fibre and phenolic acids (PAs), and their gastrointestinal modifications are critical for their bioavailability and bioactivity. We evaluated the modifications on the PA profile and gut microbiota composition of selected Nigerian wholegrains, following cooking and gastrointestinal digestion. Red fonio, red millet, red sorghum, and white corn were cooked, digested, and fermented using an in vitro colonic model. A total of 26 PA derivatives were quantified in soluble and bound fractions using Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) analysis. DNA samples were analysed using 16S rRNA amplicon sequencing to profile the microbiota composition. The results show that cooking and digestion significantly affected the levels of PAs in all grains (p ≤ 0.05) compared to raw grains. Colonic fermentation resulted in a peak of total soluble PAs at 4-6 h for red sorghum and white corn and at 24 h for red millet and red fonio. Enterobacteriaceae genera were the most abundant at 24 h in all grains studied. 3-hydroxybenzaldehyde correlated positively with the relative abundance of Dorea and the mucus-degrader bacteria Akkermansia (p ≤ 0.05), whereas hydroferulic acid and isoferulic acid levels correlated negatively with Oscillospira and Ruminococcus (p ≤ 0.05), respectively. Our data indicate that cooking, digestion, and colonic fermentation affect the release of bound PAs from wholegrains and, consequently, their metabolic conversion. Furthermore, PA fermentation in the gut is associated with potentially relevant changes in the microbiota. This in vitro study provides the basis for the design of an in vivo human intervention study that can confirm the trends herein observed but also assess the impact on health outcomes.

Conjugated Metabolites of Hydroxytyrosol and Tyrosol Contribute to the Maintenance of Nitric Oxide Balance in Human Aortic Endothelial Cells at Physiologically Relevant Concentrations.

Nitric oxide (NO) is an important signaling molecule involved in many pathophysiological processes. NO mediates vasodilation and blood flow in the arteries, and its action contributes to maintaining vascular homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to the endothelium. Dietary antioxidants and their metabolites have been found to be directly and/or indirectly involved in the modulation of the intracellular signals that lead to the production of NO. The purpose of this study was to investigate the contribution of conjugated metabolites of hydroxytyrosol (HT) and tyrosol (TYR) to the release of NO at the vascular level, and the related mechanism of action, in comparison to their parental forms. Experiments were performed in human aortic endothelial cells (HAEC) to evaluate the superoxide production, the release of NO and production of cyclic guanosine monophosphate (cGMP), the activation of serine/threonine-protein kinase 1 (Akt1), and the activation state of endothelial nitric oxide synthase (eNOS). It was observed that the tested phenolic compounds enhanced NO and cGMP concentration, inhibiting its depletion caused by superoxide overproduction. Moreover, some of them enhanced the activation of Akt (TYR, HT metabolites) and eNOS (HT, HVA, TYR-S, HT-3S). Overall, the obtained data showed that these compounds promote NO production and availability, suggesting that HT and TYR conjugated metabolites may contribute to the effects of parental extra virgin olive oil (EVOO) phenolics in the prevention of cardiovascular diseases.

Impact of lignans in oilseed mix on gut microbiome composition and enterolignan production in younger healthy and premenopausal women: an in vitro pilot study.

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.

Gastrointestinal modifications and bioavailability of brown seaweed phlorotannins and effects on inflammatory markers.

Brown seaweeds such as Ascophyllum nodosum are 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 bioactivity in vivo. Consequently, we investigated the gastrointestinal modifications in vitro of seaweed phlorotannins from A. nodosum and 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 to in 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.

Flavanone-rich citrus beverages counteract the transient decline in postprandial endothelial function in humans: a randomised, controlled, double-masked, cross-over intervention study.

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<0·05), but no dose-response effects were observed. The effects on FMD coincided with the peak of naringenin/hesperetin metabolites in circulation (7 h) and sustained levels of plasma nitrite. In summary, citrus flavanones are effective at counteracting the negative impact of a sequential double meal on human vascular function, potentially through the actions of flavanone metabolites on nitric oxide.

Thioflavones as novel neuroprotective agents.

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 (0.3µM). 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-CO moiety with a 4-CS moiety also generally enhanced neuroprotection.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

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 and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

Probiotic lactobacilli attenuate oxysterols-induced alteration of intestinal epithelial cell monolayer permeability: Focus on tight junction modulation.

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.

Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes.

The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells.

Absorption and metabolism of olive oil secoiridoids in the small intestine.

The secoiridoids 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (3,4-DHPEA-EDA) account for approximately 55 % of the phenolic content of olive oil and may be partly responsible for its reported human health benefits. We have investigated the absorption and metabolism of these secoiridoids in the upper gastrointestinal tract. Both 3,4-DHPEA-EDA and 3,4-DHPEA-EA were relatively stable under gastric conditions, only undergoing limited hydrolysis. Both secoiridoids were transferred across a human cellular model of the small intestine (Caco-2 cells). However, no glucuronide conjugation was observed for either secoiridoid during transfer, although some hydroxytyrosol and homovanillic alcohol were formed. As Caco-2 cells are known to express only limited metabolic activity, we also investigated the absorption and metabolism of secoiridoids in isolated, perfused segments of the jejunum and ileum. Here, both secoiridoids underwent extensive metabolism, most notably a two-electron reduction and glucuronidation during the transfer across both the ileum and jejunum. Unlike Caco-2 cells, the intact small-intestinal segments contain NADPH-dependent aldo-keto reductases, which reduce the aldehyde carbonyl group of 3,4-DHPEA-EA and one of the two aldeydic carbonyl groups present on 3,4-DHPEA-EDA. These reduced forms are then glucuronidated and represent the major in vivo small-intestinal metabolites of the secoiridoids. In agreement with the cell studies, perfusion of the jejunum and ileum also yielded hydroxytyrosol and homovanillic alcohol and their respective glucuronides. We suggest that the reduced and glucuronidated forms represent novel physiological metabolites of the secoiridoids that should be pursued in vivo and investigated for their biological activity.

Ferulic Acid Derivatives and Avenanthramides Modulate Endothelial Function through Maintenance of Nitric Oxide Balance in HUVEC Cells.

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.

Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity.

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.

Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers.

Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

Modulation of LPS-induced nitric oxide production in intestinal cells by hydroxytyrosol and tyrosol metabolites: Insight into the mechanism of action.

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.

Composition and content of phenolic acids and avenanthramides in commercial oat products: Are oats an important polyphenol source for consumers?

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.

Protective effect of the oligomeric acylphloroglucinols from Myrtus communis on cholesterol and human low density lipoprotein oxidation.

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.

Protective effect of vanilloids against tert-butyl hydroperoxide-induced oxidative stress in vero cells culture.

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.

Protective effect of hydroxytyrosol and its metabolite homovanillic alcohol on H(2)O(2) induced lipid peroxidation in renal tubular epithelial cells.

We investigated the capacity of hydroxytyrosol (HT), 3,4-dihydroxyphenylethanol, and homovanillic alcohol (HVA), 4-hydroxy-3-methoxy-phenylethanol, to inhibit H(2)O(2) induced oxidative damage in LLC-PK1, a porcine kidney epithelial cell line, studying the effect of H(2)O(2) on specific cell membrane lipid targets, unsaturated fatty acids and cholesterol. Exposure to H(2)O(2) induced a significant increase of the level of MDA together with a disruption of the membrane structure, with the loss of unsaturated fatty acids, cholesterol and alpha-tocopherol, and the formation of fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with HT protected renal cells from oxidative damage: the level of membrane lipids was preserved and there was no significant detection of oxidation products. HVA exerted a comparable activity, thus both HT and HVA were able to prevent in renal cells the lipid peroxidation process that plays a central role in tubular cell injury.

Modulation of intestinal epithelium homeostasis by extra virgin olive oil phenolic compounds.

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.