Role of polyphenols and polyphenol-rich foods in the modulation of PON1 activity and expression

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme involved in the protection of low-density lipoprotein and HDLs against lipid peroxidation. Several studies documented the capacity of polyphenols to stimulate PON1 transcription activation. The objective of the present review is to provide the main evidence about the role and the potential mechanism of action of polyphenols and polyphenol-rich foods in the modulation of PON1 gene expression and activity. A total of 76 in vitro and in vivo studies were included in the review. Overall, while evidence obtained in vitro is limited to quercetin and resveratrol, those deriving from animal models seem more convincing for a wide range of polyphenols but only at pharmacological doses. Evidence from human studies is promising but deserves more substantiation about the role of polyphenol-rich foods in the regulation of PON1 activity and expression. Research focused on the understanding of the structure\u2013activity relationship of polyphenols with PON1 and on the mechanisms at the base of PON1 modulation is warranted. Well-designed human intervention studies are encouraged to corroborate the findings of polyphenols also at physiological doses

Different effects of anthocyanins and phenolic acids from wild blueberry (Vaccinium angustifolium) on monocytes adhesion to endothelial cells in a TNF-alpha stimulated proinflammatory environment

SCOPE: Monocyte adhesion to the vascular endothelium is a crucial step in the early stages of atherogenesis. This study aims to investigate the capacity of an anthocyanin (ACN) and phenolic acid (PA)-rich fraction (RF) of a wild blueberry, single ACNs (cyanidin, malvidin, delphinidin) and related metabolites (protocatechuic, syringic and gallic acid) to counteract monocytes (THP-1) adhesion to endothelial cells (HUVECs) in a tumor necrosis \u3b1 (TNF-\u3b1) mediated pro-inflammatory environment. METHODS AND RESULTS: HUVECs were incubated with different concentrations (from 0.01 to 10 \u3bcg mL-1 ) of the compounds for 24 h. Labelled monocytic THP-1 cells were added to HUVECs and their adhesion was induced by TNF-\u3b1 (100 ng mL-1 ). ACN-RF reduced THP-1 adhesion to HUVECs with a maximum effect at 10 \u3bcg mL-1 (-33%). PA-RF counteracted THP-1 adhesion at 0.01, 0.1 and 1 \u3bcg mL-1 (-45%, -48.7% and -27.6%, respectively), but not at maximum concentration. Supplementation with gallic acid reduced THP-1 adhesion to HUVECs with a maximum effect at 1 \u3bcg mL-1 (-29.9%), while malvidin-3-glucoside and syringic acid increased the adhesion. No effect was observed for the other compounds. CONCLUSION: These results suggest that ACNs/PA-RF may prevent atherogenesis while the effects of the single ACNs and metabolites are controversial and merit further exploration

The central role of iron in human nutrition : from folk to contemporary medicine

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today\u2019s knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal

Effect of short-term hazelnut consumption on DNA damage and oxidized LDL in children and adolescents with primary hyperlipidemia : a randomized controlled trial

Children with primary hyperlipidemia are prone to develop premature atherosclerosis, possibly associated with increased oxidative stress. Nutritional therapy is the primary strategy in the treatment of hyperlipidemia and associated conditions. Dietary interventions with bioactive-rich foods, such as nuts, may contribute to the modulation of both lipid profile and the oxidative/antioxidant status. Our study aimed to assess the impact of a dietary intervention with hazelnuts on selected oxidative stress markers in children and adolescents with primary hyperlipidemia. A single-blind, 8-week, randomized, controlled, three-arm, parallel-group study was performed. Children and adolescents diagnosed with primary hyperlipidemia (n=60) received dietary guidelines and were randomized into three groups: group 1 received hazelnuts with skin (HZN+S), and group 2 hazelnuts without skin (HZN-S), at equivalent doses (15-30 g/day, based on body weight); group 3 (controls) received only dietary recommendations (no nuts). At baseline and after 8 weeks, plasma oxidized low-density lipoprotein (ox-LDL) concentrations, oxidative levels of DNA damage in PBMCs and potential correlation with changes in serum lipids were examined. A reduction of endogenous DNA damage by 18.9%\ub151.3% (P=.002) and 23.1%\ub147.9% (P=.007) was observed after HZN+S and HZN-S, respectively. Oxidatively induced DNA strand breaks decreased by 16.0%\ub138.2% (P=.02) following HZN+S treatment. Ox-LDL levels did not change after HZN+S intervention but positively correlated with total cholesterol and LDL cholesterol. A short-term hazelnut intervention improves cell DNA protection and resistance against oxidative stress but not ox-LDL in hyperlipidemic pediatric patients. The trial was registered at ISRCTN.com, ID no. ISRCTN12261900

Role of Arginine 285 in the Active Site of Rhodotorula gracilis d-Amino Acid Oxidase A SITE-DIRECTED MUTAGENESIS STUDY

Abstract Arg285, one of the very few conserved residues in the active site of d-amino acid oxidases, has been mutated to lysine, glutamine, aspartate, and alanine in the enzyme from the yeast Rhodotorula gracilis (RgDAAO). The mutated proteins are all catalytically competent. Mutations of Arg285 result in an increase (≈300-fold) ofK m for the d-amino acid and in a large decrease (≈500-fold) of turnover number. Stopped-flow analysis shows that the decrease in turnover is paralleled by a similar decrease in the rate of flavin reduction (k 2), the latter still being the rate-limiting step of the reaction. In agreement with data from the protein crystal structure, loss of the guanidinium group of Arg285 in the mutated DAAOs drastically reduces the binding of several carboxylic acids (e.g. benzoate). These results highlight the importance of this active site residue in the precise substrate orientation, a main factor in this redox reaction. Furthermore, Arg285 DAAO mutants have spectral properties similar to those of the wild-type enzyme, but show a low degree of stabilization of the flavin semiquinone and a change in the redox properties of the free enzyme. From this, we can unexpectedly conclude that Arg285 in the free enzyme form is involved in the stabilization of the negative charge on the N(1)-C(2)=O locus of the isoalloxazine ring of the flavin. We also suggest that the residue undergoes a conformational change in order to bind the carboxylate portion of the substrate/ligand in the complexed enzyme

Effect of hazelnut on serum lipid profile and fatty acid composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia : a randomized controlled trial

Background & aim: Regular intake of nuts improves lipid profile and thus reduces the cardiovascular (CV) risk associated with hyperlipidemia. The aim of the study was to investigate the effect of a dietary intervention with hazelnuts (HZNs, 15-30 g/day, depending on patient weight) on serum lipid profile, anthropometric parameters and fatty acids (FAs) composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia. Methods: Eight-week randomized, single blind, controlled, three-arm, parallel-group study. Sixty-six subjects were enrolled and randomized in 3 groups receiving: 1) hazelnuts with skin (HZN+S); 2) hazelnuts without skin (HZN-S); 3) dietary advices for hyperlipidemia only (controls). Before and after intervention, clinical parameters were measured and blood samples were collected for the evaluation of serum lipid levels and phospholipid FA composition of erythrocytes. Results: Two-way ANOVA showed a significant effect of time on serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)/LDL-C ratio and non-HDL-C (p < 0.001), but not of treatment and time x treatment interaction. In particular, HZN+S and HZN-S significantly reduced the concentrations of LDL-C and increased HDL-C/LDL-C ratio. HZNs also had a favorable impact on FAs composition of erythrocyte phospholipids, as demonstrated by time x treatment interaction, with a significant increase of monounsaturated fatty acids (MUFAs) (p = 0.008) and MUFAs/saturated fatty acids (SFAs) ratio (p = 0.002) with respect to the control group. Conclusions: For the first time, we documented a positive effect of HZN consumption on lipid profile and FA composition of erythrocyte phospholipids in children with primary hyperlipidemia. Further studies are encouraged to better define HZN impact on the markers of CV risk in this population

Six-Week Consumption of a Wild Blueberry Powder Drink Increases Bifidobacteria in the Human Gut

Wild blueberries are a rich source of polyphenols and other compounds that are highly metabolized by the intestinal microbiota and may, at the same time, affect the intestinal environment itself. A repeated-measure, crossover dietary intervention on human volunteers was designed to study the effect of six week consumption of a wild blueberry (Vaccinium angustifolium) drink, versus a placebo drink, in modulating the intestinal microbiota. Relative to total eubacteria, Bifidobacterium spp. significantly increased following blueberry treatment (P 65 0.05), while Lactobacillus acidophilus increased after both treatments (P 65 0.05). No significant differences were observed for Bacteroides spp., Prevotella spp., Enterococcus spp., and Clostridium coccoides. Bifidobacteria, which have been largely proposed to be of benefit for the host, appeared to be selectively favored suggesting an important role for the polyphenols and fiber present in wild blueberries. Results obtained suggest that regular consumption of a wild blueberry drink can positively modulate the composition of the intestinal microbiota

Analysis of cadmium translocation, partitioning and tolerance in six barley (Hordeum vulgare L.) cultivars as a function of thiol metabolism

Six barley cultivars widely differing for cadmium (Cd) tolerance, partitioning, and translocation were analyzed in relation to their thiol metabolism. Results indicated that Cd tolerance was not clearly related to the total amount of Cd absorbed by plants, resulting instead closely dependent on the capacity of the cultivars to trap the metal into the roots. Such behaviors suggested the existence of root mechanisms preserving shoots from Cd-induced oxidative damages, as indicated by the analysis of thiobarbituric acid-reactive substances \u2014diagnostic indicators of oxidative stress\u2014whose increases in the shoots were negatively related to Cd root retention and tolerance. Cd exposure differentially affected glutathione (GSH) and phytochelatin (PC) levels in the tissues of each barley cultivar. The capacity to produce PCs appeared as a specific characteristic of each barley cultivar, since it did not depend on Cd concentration in the roots and resulted negatively related to the concentration of the metal in the shoots, indicating the existence of a cultivar-specific interference of Cd on GSH biosynthesis, as confirmed by the existence of close positive linear relationships between the effect of Cd on GSH levels and PC accumulation in both roots and shoots. The six barley cultivars also differed for their capacity to load Cd ions into the xylem, which was negatively related to PC content in the roots. Taken as a whole, these data indicated that the different capacity of each cultivar to maintain GSH homeostasis under Cd stress may strongly affect PC accumulation and, thus, Cd tolerance and translocation

Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors

Purpose Wild blueberries (WB) (Vaccinium angustifolium) are rich sources of polyphenols, such as flavonols, phenolic acids and anthocyanins (ACNs), reported to decrease the risk of cardiovascular and degenerative diseases. This study investigated the effect of regular consumption of a WB or a placebo (PL) drink on markers of oxidative stress, inflammation and endothelial function in subjects with risk factors for cardiovascular disease. Methods Eighteen male volunteers (ages 47.8 ? 9.7 years; body mass index 24.8 ? 2.6 kg/m2) received according to a cross-over design, a WB (25 g freeze-dried powder, providing 375 mg of ACNs) or a PL drink for 6 weeks, spaced by a 6-week wash-out. Endogenous and oxidatively induced DNA damage in blood mononuclear cells, serum interleukin levels, reactive hyperemia index, nitric oxide, soluble vascular adhesion molecule concentration and other variables were analyzed. In conclusion, the consumption of the WB drink for 6 weeks significantly reduced the levels of oxidized DNA bases and increased the resistance to oxidatively induced DNA damage. Future studies should address in greater detail the role of WB in endothelial functio