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Open AccessArticle In Vivo Protective Effects of Nootkatone against Particles-Induced Lung Injury Caused by Diesel Exhaust Is Mediated via the NF-κB Pathway

by Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Naserddine Hamadi and Badreldin H. Ali

Nutrients 2018, 10(3), 263; https://doi.org/10.3390/nu10030263

Received: 2 January 2018 / Revised: 18 January 2018 / Accepted: 23 January 2018 / Published: 26 February 2018

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Abstract

Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity

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Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects. Full article

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Open AccessArticle Association of Vitamin E Levels with Metabolic Syndrome, and MRI-Derived Body Fat Volumes and Liver Fat Content

by Sabina Waniek, Romina di Giuseppe, Sandra Plachta-Danielzik, Ilka Ratjen, Gunnar Jacobs, Manja Koch, Jan Borggrefe, Marcus Both, Hans-Peter Müller, Jan Kassubek, Ute Nöthlings, Tuba Esatbeyoglu, Sabrina Schlesinger, Gerald Rimbach and Wolfgang Lieb

Nutrients 2017, 9(10), 1143; https://doi.org/10.3390/nu9101143

Received: 21 July 2017 / Revised: 2 October 2017 / Accepted: 11 October 2017 / Published: 18 October 2017

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Abstract

We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposityrelated traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean

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We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposityrelated traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women). Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD), metabolic syndrome (MetS), and its individual components. The α- tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21–2.76 for 3rd vs. 1st tertile), and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23–2.84 for 3rd vs. 1st tertile). α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05). No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies. Full article

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Open AccessArticle The Effect of Consumption of Citrus Fruit and Olive Leaf Extract on Lipid Metabolism

by Nicola Merola, Julián Castillo, Obdulio Benavente-García, Gaspar Ros and Gema Nieto

Nutrients 2017, 9(10), 1062; https://doi.org/10.3390/nu9101062

Received: 5 July 2017 / Revised: 30 August 2017 / Accepted: 19 September 2017 / Published: 26 September 2017

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Abstract

Citrus fruit and olive leaves are a source of bioactive compounds such as biophenols which have been shown to ameliorate obesity-related conditions through their anti-hyperlipidemic and anti-inflammatory effect, and by regulating lipoproteins and cholesterol body levels. Citrolive™ is a commercial extract which is

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Citrus fruit and olive leaves are a source of bioactive compounds such as biophenols which have been shown to ameliorate obesity-related conditions through their anti-hyperlipidemic and anti-inflammatory effect, and by regulating lipoproteins and cholesterol body levels. Citrolive™ is a commercial extract which is obtained from the combination of both citrus fruit and olive leaf extracts; hence, it is hypothesised that Citrolive™ may moderate metabolic disorders that are related to obesity and their complications. Initially, an in vitro study of the inhibition of pancreatic lipase activity was made, however, no effect was found. Both preliminary and long-term evaluations of Citrolive™ on lipid metabolism were conducted in an animal model using Wistar rats. In the preliminary in vivo screening, Citrolive™ was tested on postprandial plasma triglyceride level after the administration of an oil emulsion, and a significant reduction in postprandial triacylglycerol (TAG) levels was observed. In the long-term study, Citrolive™ was administered for 60 days on Wistar rats that were fed a high-fat diet. During the study, several associated lipid metabolism indicators were analysed in blood and faeces. At the end of the experiment, the livers were removed and weighed for group comparison. Citrolive™ treatment significantly reduced the liver-to-body-weight ratio, as supported by reduced plasma transaminases compared with control, but insignificantly reduced plasma low density lipoprotein (LDL) and postprandial TAG plasma levels. In addition, faecal analysis showed that the treatment significantly increased total cholesterol excretion. On the other hand, no effect was found on faecal TAG and pancreatic lipase in vitro. In conclusion, treatment ameliorates liver inflammation symptoms that are worsened by the effects of high fat diet. Full article

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Open AccessArticle Comparison of Australian Recommended Food Score (ARFS) and Plasma Carotenoid Concentrations: A Validation Study in Adults

by Lee Ashton, Rebecca Williams, Lisa Wood, Tracy Schumacher, Tracy Burrows, Megan Rollo, Kristine Pezdirc, Robin Callister and Clare Collins

Nutrients 2017, 9(8), 888; https://doi.org/10.3390/nu9080888

Received: 24 July 2017 / Revised: 10 August 2017 / Accepted: 15 August 2017 / Published: 17 August 2017

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Abstract

Diet quality indices can predict nutritional adequacy of usual intake, but validity should be determined. The aim was to assess the validity of total and sub-scale score within the Australian Recommended Food Score (ARFS), in relation to fasting plasma carotenoid concentrations. Diet quality

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Diet quality indices can predict nutritional adequacy of usual intake, but validity should be determined. The aim was to assess the validity of total and sub-scale score within the Australian Recommended Food Score (ARFS), in relation to fasting plasma carotenoid concentrations. Diet quality and fasting plasma carotenoid concentrations were assessed in 99 overweight and obese adults (49.5% female, aged 44.6 ± 9.9 years) at baseline and after three months (198 paired observations). Associations were assessed using Spearman’s correlation coefficients and regression analysis, and agreement using weighted kappa (K_w). Small, significantly positive correlations were found between total ARFS and plasma concentrations of total carotenoids (r = 0.17, p < 0.05), β-cryptoxanthin (r = 0.18, p < 0.05), β-carotene (r = 0.20, p < 0.01), and α-carotene (r = 0.19, p < 0.01). Significant agreement between ARFS categories and plasma carotenoid concentrations was found for total carotenoids (K_w 0.12, p = 0.02), β-carotene (K_w 0.14, p < 0.01), and α-carotene (K_w 0.13, p < 0.01). In fully-adjusted regression models the only signification association with ARFS total score was for α-carotene (β = 0.19, p < 0.01), while ARFS meat and fruit sub-scales demonstrated significant relationships with α-carotene, β-carotene, and total carotenoids (p < 0.05). The weak associations highlight the issues with self-reporting dietary intakes in overweight and obese populations. Further research is required to evaluate the use of the ARFS in more diverse populations. Full article

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Open AccessArticle Effects of Pomegranate Juice Supplementation on Oxidative Stress Biomarkers Following Weightlifting Exercise

by Achraf Ammar, Mouna Turki, Omar Hammouda, Hamdi Chtourou, Khaled Trabelsi, Mohamed Bouaziz, Osama Abdelkarim, Anita Hoekelmann, Fatma Ayadi, Nizar Souissi, Stephen J. Bailey, Tarak Driss and Sourour Yaich

Nutrients 2017, 9(8), 819; https://doi.org/10.3390/nu9080819

Received: 9 June 2017 / Revised: 15 July 2017 / Accepted: 21 July 2017 / Published: 29 July 2017

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Abstract

The aim of this study was to test the hypothesis that pomegranate juice supplementation would blunt acute and delayed oxidative stress responses after a weightlifting training session. Nine elite weightlifters (21.0 ± 1 years) performed two Olympic-Weightlifting sessions after ingesting either the placebo

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The aim of this study was to test the hypothesis that pomegranate juice supplementation would blunt acute and delayed oxidative stress responses after a weightlifting training session. Nine elite weightlifters (21.0 ± 1 years) performed two Olympic-Weightlifting sessions after ingesting either the placebo or pomegranate juice supplements. Venous blood samples were collected at rest and 3 min and 48 h after each session. Compared to the placebo condition, pomegranate juice supplementation attenuated the increase in malondialdehyde (−12.5%; p < 0.01) and enhanced the enzymatic (+8.6% for catalase and +6.8% for glutathione peroxidase; p < 0.05) and non-enzymatic (+12.6% for uric acid and +5.7% for total bilirubin; p < 0.01) antioxidant responses shortly (3 min) after completion of the training session. Additionally, during the 48 h recovery period, pomegranate juice supplementation accelerated (p < 0.05) the recovery kinetics of the malondialdehyde (5.6%) and the enzymatic antioxidant defenses compared to the placebo condition (9 to 10%). In conclusion, supplementation with pomegranate juice has the potential to attenuate oxidative stress by enhancing antioxidant responses assessed acutely and up to 48 h following an intensive weightlifting training session. Therefore, elite weightlifters might benefit from blunted oxidative stress responses following intensive weightlifting sessions, which could have implications for recovery between training sessions. Full article

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Open AccessArticle Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated Apoptosis

by Chian Ju Jong, Takashi Ito, Howard Prentice, Jang-Yen Wu and Stephen W. Schaffer

Nutrients 2017, 9(8), 795; https://doi.org/10.3390/nu9080795

Received: 18 May 2017 / Revised: 18 July 2017 / Accepted: 19 July 2017 / Published: 25 July 2017

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Abstract

Taurine is a ubiquitous sulfur-containing amino acid found in high concentration in most tissues. Because of its involvement in fundamental physiological functions, such as regulating respiratory chain activity, modulating cation transport, controlling inflammation, altering protein phosphorylation and prolonging lifespan, taurine is an important

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Taurine is a ubiquitous sulfur-containing amino acid found in high concentration in most tissues. Because of its involvement in fundamental physiological functions, such as regulating respiratory chain activity, modulating cation transport, controlling inflammation, altering protein phosphorylation and prolonging lifespan, taurine is an important nutrient whose deficiency leads to severe pathology and cell death. However, the mechanism by which taurine deficiency causes cell death is inadequately understood. Therefore, the present study examined the hypothesis that overproduction of reactive oxygen species (ROS) by complex I of the respiratory chain triggers mitochondria-dependent apoptosis in hearts of taurine transporter knockout (TauTKO) mice. In support of the hypothesis, a 60% decrease in mitochondrial taurine content of 3-month-old TauTKO hearts was observed, which was associated with diminished complex I activity and the onset of mitochondrial oxidative stress. Oxidative damage to stressed mitochondria led to activation of a caspase cascade, with stimulation of caspases 9 and 3 prevented by treatment of 3-month-old TauTKO mice with the mitochondria specific antioxidant, MitoTempo. In 12 month-old, but not 3-month-old, TauTKO hearts, caspase 12 activation contributes to cell death, revealing a pathological role for endoplasmic reticulum (ER) stress in taurine deficient, aging mice. Thus, taurine is a cytoprotective nutrient that ensures normal mitochondrial and ER function, which is important for the reduction of risk for apoptosis and premature death. Full article

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Open AccessArticle Quercetin and Green Tea Extract Supplementation Downregulates Genes Related to Tissue Inflammatory Responses to a 12-Week High Fat-Diet in Mice

by Lynn Cialdella-Kam, Sujoy Ghosh, Mary Pat Meaney, Amy M. Knab, R. Andrew Shanely and David C. Nieman

Nutrients 2017, 9(7), 773; https://doi.org/10.3390/nu9070773

Received: 19 June 2017 / Revised: 7 July 2017 / Accepted: 13 July 2017 / Published: 19 July 2017

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Abstract

Quercetin (Q) and green tea extract (E) are reported to counter insulin resistance and inflammation and favorably alter fat metabolism. We investigated whether a mixture of E + Q (EQ) could synergistically influence metabolic and inflammation endpoints in a high-fat diet (HFD) fed

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Quercetin (Q) and green tea extract (E) are reported to counter insulin resistance and inflammation and favorably alter fat metabolism. We investigated whether a mixture of E + Q (EQ) could synergistically influence metabolic and inflammation endpoints in a high-fat diet (HFD) fed to mice. Male C57BL/6 mice (n = 40) were put on HFD (fat = 60%kcal) for 12 weeks and randomly assigned to Q (25 mg/kg of body weight (BW)/day), E (3 mg of epigallocatechin gallate/kg BW/day), EQ, or control groups for four weeks. At 16 weeks, insulin sensitivity was measured via the glucose tolerance test (GTT), followed by area-under-the-curve (AUC) estimations. Plasma cytokines and quercetin were also measured, along with whole genome transcriptome analysis and real-time polymerase chain reaction (qPCR) on adipose, liver, and skeletal muscle tissues. Univariate analyses were conducted via analysis of variance (ANOVA), and whole-genome expression profiles were examined via gene set enrichment. At 16 weeks, plasma quercetin levels were higher in Q and EQ groups vs. the control and E groups (p < 0.05). Plasma cytokines were similar among groups (p > 0.05). AUC estimations for GTT was 14% lower for Q vs. E (p = 0.0311), but non-significant from control (p = 0.0809). Genes for cholesterol metabolism and immune and inflammatory response were downregulated in Q and EQ groups vs. control in adipose tissue and soleus muscle tissue. These data support an anti-inflammatory role for Q and EQ, a result best captured when measured with tissue gene downregulation in comparison to changes in plasma cytokine levels. Full article

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Open AccessArticle Lack of Additive Effects of Resveratrol and Energy Restriction in the Treatment of Hepatic Steatosis in Rats

by Iñaki Milton-Laskibar, Leixuri Aguirre, Alfredo Fernández-Quintela, Anabela P. Rolo, João Soeiro Teodoro, Carlos M. Palmeira and María P. Portillo

Nutrients 2017, 9(7), 737; https://doi.org/10.3390/nu9070737

Received: 30 May 2017 / Revised: 3 July 2017 / Accepted: 5 July 2017 / Published: 11 July 2017

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Abstract

The aims of the present study were to analyze the effect of resveratrol on liver steatosis in obese rats, to compare the effects induced by resveratrol and energy restriction and to research potential additive effects. Rats were initially fed a high-fat high-sucrose diet

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The aims of the present study were to analyze the effect of resveratrol on liver steatosis in obese rats, to compare the effects induced by resveratrol and energy restriction and to research potential additive effects. Rats were initially fed a high-fat high-sucrose diet for six weeks and then allocated in four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy restricted group and a group submitted to energy restriction and treated with resveratrol. We measured liver triacylglycerols, transaminases, FAS, MTP, CPT1a, CS, COX, SDH and ATP synthase activities, FATP2/FATP5, DGAT2, PPARα, SIRT1, UCP2 protein expressions, ACC and AMPK phosphorylation and PGC1α deacetylation. Resveratrol reduced triacylglycerols compared with the controls, although this reduction was lower than that induced by energy restriction. The mechanisms of action were different. Both decreased protein expression of fatty acid transporters, thus suggesting reduced fatty acid uptake from blood stream and liver triacylglycerol delivery, but only energy restriction reduced the assembly. These results show that resveratrol is useful for liver steatosis treatment within a balanced diet, although its effectiveness is lower than that of energy restriction. However, resveratrol is unable to increase the reduction in triacylglycerol content induced by energy restriction. Full article

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Open AccessArticle Dietary Vitamin C, E and β-Carotene Intake Does Not Significantly Affect Plasma or Salivary Antioxidant Indices and Salivary C-Reactive Protein in Older Subjects

by Anna Gawron-Skarbek, Agnieszka Guligowska, Anna Prymont-Przymińska, Małgorzata Godala, Agnieszka Kolmaga, Dariusz Nowak, Franciszek Szatko and Tomasz Kostka

Nutrients 2017, 9(7), 729; https://doi.org/10.3390/nu9070729

Received: 1 June 2017 / Revised: 29 June 2017 / Accepted: 6 July 2017 / Published: 9 July 2017

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Abstract

It is not clear whether habitual dietary intake influences the antioxidant or inflammatory status. The aim of the present study was to assess the impact of antioxidative vitamins C, E, and β-carotene obtained from daily food rations on plasma and salivary Total Antioxidant

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It is not clear whether habitual dietary intake influences the antioxidant or inflammatory status. The aim of the present study was to assess the impact of antioxidative vitamins C, E, and β-carotene obtained from daily food rations on plasma and salivary Total Antioxidant Capacity (TAC), uric acid and salivary C-reactive protein (CRP). The study involved 80 older subjects (66.9 ± 4.3 years), divided into two groups: group 1 (n = 43) with lower and group 2 (n = 37) with higher combined vitamins C, E and β-carotene intake. A 24-h dietary recall was obtained from each individual. TAC was assessed simultaneously with two methods in plasma (Ferric Reducing Ability of Plasma—FRAP, 2.2-diphenyl-1-picryl-hydrazyl—DPPH) and in saliva (FRAS and DPPHS test). Lower vitamin C intake corresponded to higher FRAS. There were no other correlations between vitamins C, E or β-carotene intake and antioxidant indices. Salivary CRP was not related to any antioxidant indices. FRAS was decreased in group 2 (p < 0.01) but no other group differences for salivary or for plasma antioxidant parameters and salivary CRP were found. Habitual, not extra supplemented dietary intake does not significantly affect plasma or salivary TAC and salivary CRP. Full article

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Open AccessArticle Ferulic Acid on Glucose Dysregulation, Dyslipidemia, and Inflammation in Diet-Induced Obese Rats: An Integrated Study

by Norma Julieta Salazar-López, Humberto Astiazarán-García, Gustavo A. González-Aguilar, Guadalupe Loarca-Piña, Josafat-Marina Ezquerra-Brauer, J. Abraham Domínguez Avila and Maribel Robles-Sánchez

Nutrients 2017, 9(7), 675; https://doi.org/10.3390/nu9070675

Received: 26 May 2017 / Revised: 20 June 2017 / Accepted: 21 June 2017 / Published: 29 June 2017

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Abstract

Obesity is considered to be a low-grade chronic inflammatory process, which is associated with cardiovascular and metabolic diseases. An integral evaluation of the effects of ferulic acid on biomarkers of glucose dysregulation, dyslipidemia, inflammation, and antioxidant potential induced by a high-fat diet (HFD)

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Obesity is considered to be a low-grade chronic inflammatory process, which is associated with cardiovascular and metabolic diseases. An integral evaluation of the effects of ferulic acid on biomarkers of glucose dysregulation, dyslipidemia, inflammation, and antioxidant potential induced by a high-fat diet (HFD) in rats was carried out. Three groups of male Wistar rats (six per group) consumed a basal diet (BD), which was supplemented with either lard at 310 g/kg (HFD) or lard and ferulic acid at 2 g/kg (HFD + FA), ad libitum for eight weeks. Body weight gain, hyperplasia, and hypertrophy in abdominal fat tissues were higher in the HFD group than in the HFD+FA group. The rats fed a HFD + FA significantly inhibited the increase in plasma lipids and glucose, compared with the HFD group. Biomarkers associated with inflammation were found at higher concentrations in the serum of rats fed a HFD than the HFD + FA group. Plasma antioxidant levels were lower in HFD rats compared to rats fed the HFD + FA. These results suggest that ferulic acid improves the obesogenic status induced by HFD, and we elucidated the integral effects of ferulic acid on a biological system. Full article

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Open AccessArticle Lipid Accumulation in HepG2 Cells Is Attenuated by Strawberry Extract through AMPK Activation

by Tamara Y. Forbes-Hernández, Francesca Giampieri, Massimiliano Gasparrini, Sadia Afrin, Luca Mazzoni, Mario D. Cordero, Bruno Mezzetti, José L. Quiles and Maurizio Battino

Nutrients 2017, 9(6), 621; https://doi.org/10.3390/nu9060621

Received: 9 May 2017 / Revised: 12 June 2017 / Accepted: 13 June 2017 / Published: 16 June 2017

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Abstract

Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on

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Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2). For such purpose, the lipid profile and the expression of proteins metabolically related to AMPK were determined on cells lysates. The results demonstrated that strawberry methanolic extract decreased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides levels (up to 0.50-, 0.30-, and 0.40-fold, respectively) while it stimulated the p-AMPK/AMPK expression (up to 3.06-fold), compared to the control. AMPK stimulation led to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively. Strawberry treatment also entailed a 4.34-, 2.37-, and 2.47-fold overexpression of LDL receptor, sirtuin 1 (Sirt1), and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), respectively, compared to control. The observed results were counteracted by treatment with compound C, an AMPK pharmacological inhibitor, confirming that multiple effects of strawberries on lipid metabolism are mediated by the activation of this protein. Full article

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Open AccessArticle Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage

by Massimiliano Gasparrini, Tamara Y. Forbes-Hernandez, Sadia Afrin, Patricia Reboredo-Rodriguez, Danila Cianciosi, Bruno Mezzetti, Josè L. Quiles, Stefano Bompadre, Maurizio Battino and Francesca Giampieri

Nutrients 2017, 9(6), 605; https://doi.org/10.3390/nu9060605

Received: 15 May 2017 / Revised: 5 June 2017 / Accepted: 8 June 2017 / Published: 14 June 2017

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Abstract

Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema,

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Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 μg/mL)-based formulations supplemented with Coenzyme Q₁₀ (100 μg/mL) and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS) production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q₁₀ provided a significant (p < 0.05) photoprotective effect, reducing cell death and ROS, increasing antioxidant defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents. Full article

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Open AccessArticle Alpha- and Gamma-Tocopherol and Telomere Length in 5768 US Men and Women: A NHANES Study

by Larry A. Tucker

Nutrients 2017, 9(6), 601; https://doi.org/10.3390/nu9060601

Received: 7 June 2017 / Revised: 7 June 2017 / Accepted: 8 June 2017 / Published: 13 June 2017

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Abstract

Antioxidants have a number of potential health benefits. The present investigation was designed to determine the relationship between serum alpha- and gamma-tocopherol levels (powerful antioxidants), and leukocyte telomere length (a biomarker of biological aging). A cross-sectional design was employed to study 5768 adults

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Antioxidants have a number of potential health benefits. The present investigation was designed to determine the relationship between serum alpha- and gamma-tocopherol levels (powerful antioxidants), and leukocyte telomere length (a biomarker of biological aging). A cross-sectional design was employed to study 5768 adults from the National Health and Nutrition Examination Survey (NHANES). DNA was obtained via blood samples. Telomere length was assessed using the quantitative polymerase chain reaction method. Serum concentrations of alpha- and gamma-tocopherol were measured using high performance liquid chromatography (HPLC). Results showed that for each one-year increase in age, telomeres were 15.6 base pairs shorter (F = 410.4, p < 0.0001). After adjusting for differences in the demographic covariates, for each µg/dL higher level of gamma-tocopherol, telomeres were 0.33 base pairs shorter (F = 7.1, p = 0.0126). Telomeres were approximately 1 year shorter (15.6 base pairs) for each increment of 47.3 to 55.7 µg/dL of gamma-tocopherol in the blood, depending on the variables controlled. Adults at the 75th percentile of gamma-tocopherol had 2.8–3.4 years greater cellular aging than those at the 25th percentile, depending on the covariates in the model. However, alpha-tocopherol was not related to telomere length. Evidently, gamma-tocopherol levels, but not alpha-tocopherol, account for meaningful increases in biological aging. Full article

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Open AccessArticle Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition

by Juhyun Song and Oh Yoen Kim

Nutrients 2017, 9(6), 593; https://doi.org/10.3390/nu9060593

Received: 30 April 2017 / Revised: 6 June 2017 / Accepted: 8 June 2017 / Published: 10 June 2017

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Abstract

Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival

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Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling. Full article

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Open AccessArticle Curcumin Anti-Apoptotic Action in a Model of Intestinal Epithelial Inflammatory Damage

by Claudia Loganes, Sara Lega, Matteo Bramuzzo, Liza Vecchi Brumatti, Elisa Piscianz, Erica Valencic, Alberto Tommasini and Annalisa Marcuzzi

Nutrients 2017, 9(6), 578; https://doi.org/10.3390/nu9060578

Received: 24 April 2017 / Revised: 27 May 2017 / Accepted: 1 June 2017 / Published: 6 June 2017

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Abstract

The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to

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The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to undergo apoptotic changes that can reproduce the damage of intestinal epithelia exposed to inflammatory cytokines. In this model, we measured the effect of curcumin (curcuminoid from Curcuma Longa) added as a pre-treatment at different time intervals before stimulation with IFNγ. Curcumin administration to HT29 culture before the inflammatory stimulus IFNγ reduced the cell apoptosis rate. This effect gradually declined with the reduction of the curcumin pre-incubation time. This anti-apoptotic action by curcumin pre-treatment was paralleled by a reduction of secreted IL7 in the HT29 culture media, while there was no relevant change in the other cytokine levels. Even though curcumin pre-administration did not impact the activation of the NF-κB pathway, a slight effect on the phosphorylation of proteins in this inflammatory signaling pathway was observed. In conclusion, curcumin pre-treatment can protect intestinal cells from inflammatory damage. These results can be the basis for studying the preventive role of curcumin in inflammatory bowel diseases. Full article

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Open AccessArticle Different Intestinal Microbial Profile in Over-Weight and Obese Subjects Consuming a Diet with Low Content of Fiber and Antioxidants

by Tania Fernández-Navarro, Nuria Salazar, Isabel Gutiérrez-Díaz, Clara G. de los Reyes-Gavilán, Miguel Gueimonde and Sonia González

Nutrients 2017, 9(6), 551; https://doi.org/10.3390/nu9060551

Received: 18 April 2017 / Revised: 18 May 2017 / Accepted: 23 May 2017 / Published: 27 May 2017

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Abstract

Obesity has been related to an increased risk of multiple diseases in which oxidative stress and inflammation play a role. Gut microbiota has emerged as a mediator in this interaction, providing new mechanistic insights at the interface between fat metabolism dysregulation and obesity

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Obesity has been related to an increased risk of multiple diseases in which oxidative stress and inflammation play a role. Gut microbiota has emerged as a mediator in this interaction, providing new mechanistic insights at the interface between fat metabolism dysregulation and obesity development. Our aim was to analyze the interrelationship among obesity, diet, oxidative stress, inflammation and the intestinal microbiota in 68 healthy adults (29.4% normal-weight). Diet was assessed through a food frequency questionnaire and converted into nutrients and dietary compounds using food composition tables. The intestinal microbiota was assessed by quantitative PCR, fecal short chain fatty acids by gas chromatography and serum biomarkers by standard protocols. Higher levels of malondialdehyde (MDA), C reactive protein (CRP), serum leptin, glucose, fat percentage and the intestinal Lactobacillus group were found in the obese people. Cluster analysis of body mass index, fat mass, glucose, LDL/HDL ratio, leptin, MDA and CRP classified the subjects into two groups. The levels of the intestinal Bacteroides-Prevotella-Porphyromonas group were lower in the cluster and linked to a higher pro-oxidant and pro-inflammatory status, whose individuals also had lower intake of fruits, dried fruits, and fish. These results could be useful for designing strategies targeted to obesity prevention. Full article

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Open AccessArticle Improvement of Antioxidant Defences and Mood Status by Oral GABA Tea Administration in a Mouse Model of Post-Stroke Depression

by Maria Daglia, Arianna Di Lorenzo, Seyed Fazel Nabavi, Antoni Sureda, Sedigheh Khanjani, Akbar Hajizadeh Moghaddam, Nady Braidy and Seyed Mohammad Nabavi

Nutrients 2017, 9(5), 446; https://doi.org/10.3390/nu9050446

Received: 26 February 2017 / Revised: 2 April 2017 / Accepted: 24 April 2017 / Published: 29 April 2017

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Abstract

Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing

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Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation. Methods: Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo. Results: GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity. Conclusions: Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD. Full article

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Open AccessArticle Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

by Mandy M. Liu, Kevin M. Huang, Steven Yeung, Andy Chang, Suhui Zhang, Nan Mei, Cyrus Parsa, Robert Orlando and Ying Huang

Nutrients 2017, 9(3), 300; https://doi.org/10.3390/nu9030300

Received: 9 February 2017 / Revised: 12 March 2017 / Accepted: 12 March 2017 / Published: 18 March 2017

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Abstract

Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous

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Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT’s activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF)-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in ‘Sensitivity to Carcinogenesis’ (SENCAR) mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA), and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB. Full article

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Open AccessArticle Enantioselective Modulatory Effects of Naringenin Enantiomers on the Expression Levels of miR‐17‐3p Involved in Endogenous Antioxidant Defenses

by Valeria Curti, Arianna Di Lorenzo, Daniela Rossi, Emanuela Martino, Enrica Capelli, Simona Collina and Maria Daglia

Nutrients 2017, 9(3), 215; https://doi.org/10.3390/nu9030215

Received: 28 November 2016 / Accepted: 24 February 2017 / Published: 28 February 2017

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Abstract

Naringenin is a flavanone present in citrus fruit as a mixture of chiral isomers. The numerous biological properties attributed to this compound include antioxidant and anti‐inflammatory activities, even though the molecular mechanisms of these remain unknown. This study aims to evaluate the effects

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Naringenin is a flavanone present in citrus fruit as a mixture of chiral isomers. The numerous biological properties attributed to this compound include antioxidant and anti‐inflammatory activities, even though the molecular mechanisms of these remain unknown. This study aims to evaluate the effects of racemic and enantiomeric naringenin on the expression levels of miR‐17‐3p, miR‐25‐5p and relative mRNA targets, to elucidate the mechanisms underlying these antioxidant and anti‐inflammatory properties. Caco‐2 cells, a well characterized in vitro model which mimics the intestinal barrier, were treated with subtoxic concentrations of racemate and enantiomers. The expression levels of miR‐17‐3p and miR‐25‐5p were determined by Real‐Time PCR and were found to be decreased for both miRNAs. miR‐17‐3p behavior was in agreement with the increased levels of target mRNAs coding for two antioxidant enzymes, manganese‐dependent superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPx2), while expression levels of miR‐25‐5p were not in agreement with its target mRNAs, coding for two pro‐inflammatory cytokines, Tumor necrosis factor‐alpha (TNF‐α) and Interleukin‐6 (IL‐6). These results lead to the conclusion that naringenin could exert its antioxidant activity through epigenetic regulation operated by miRNAs, while anti‐inflammatory activity is regulated by other miRNAs and/or mechanisms. Full article

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Open AccessArticle The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

by Tingting Ren, Juanjuan Zhu, Lili Zhu and Mingliang Cheng

Nutrients 2017, 9(3), 198; https://doi.org/10.3390/nu9030198

Received: 17 December 2016 / Revised: 14 February 2017 / Accepted: 21 February 2017 / Published: 27 February 2017

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Abstract

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be

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Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway via PPAR-α. Full article

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Open AccessArticle Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q₁₀ Addition

by Alfonso Varela-López, Julio J. Ochoa, José M. Llamas-Elvira, Magdalena López-Frías, Elena Planells, MCarmen Ramirez-Tortosa, Cesar L. Ramirez-Tortosa, Francesca Giampieri, Maurizio Battino and José L. Quiles

Nutrients 2017, 9(2), 176; https://doi.org/10.3390/nu9020176

Received: 11 November 2016 / Revised: 24 January 2017 / Accepted: 13 February 2017 / Published: 22 February 2017

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Abstract

During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil

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During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q₁₀ (CoQ₁₀), to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA)-based diet for bone mineral density (BMD) preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F₂-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ₁₀ respect than their younger counterparts, whereas older animals receiving CoQ₁₀ showed the highest BMD. F₂-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ₁₀ prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ₁₀ supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals. Full article

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Open AccessArticle Oxyresveratrol Supplementation to C57bl/6 Mice Fed with a High-Fat Diet Ameliorates Obesity-Associated Symptoms

by Hui Yuan Tan, Iris Mei Ying Tse, Edmund Tsze Shing Li and Mingfu Wang

Nutrients 2017, 9(2), 147; https://doi.org/10.3390/nu9020147

Received: 16 January 2017 / Revised: 6 February 2017 / Accepted: 13 February 2017 / Published: 16 February 2017

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Abstract

Oxyresveratrol has been proven effective in inhibiting adipogenesis in a 3T3-L1 cell model. We investigated the preventive effect of oxyresveratrol supplementation on obesity development in high-fat diet-fed mice. Male C57bl/6 mice were randomly subjected to control (5% fat by weight, LF), high-fat (30%

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Oxyresveratrol has been proven effective in inhibiting adipogenesis in a 3T3-L1 cell model. We investigated the preventive effect of oxyresveratrol supplementation on obesity development in high-fat diet-fed mice. Male C57bl/6 mice were randomly subjected to control (5% fat by weight, LF), high-fat (30% fat by weight, HF), and high-fat supplemented with 0.25% and 0.5% oxyresveratrol (OXY1 and OXY2, respectively) diet groups for eight weeks. Oxyresveratrol supplementation effectively alleviated obesity-associated symptoms such as insulin resistance, hyperglycemia, and hepatic steatosis in high-fat diet-fed mice. Compared to the high-fat diet group, oxyresveratrol supplementation suppressed expression of glucose-6-phosphatase, sterol regulatory element-binding proteins 1, fatty acid synthase and CCAAT/Enhancer-binding proteins α, and elevated AMP-activated protein kinase (α2-catalytic subunit) level in liver, upregulated insulin-dependent glucose transporter type 4 level in adipose tissue, and increased expression of insulin receptor substrate 1, insulin-dependent glucose transporter type 4, AMP-activated protein kinase α, peroxisome proliferator-activated receptor γ coactivator-1α, and sirtuin 1 in muscle to regulate lipid and glucose homeostasis in these tissues. This study demonstrated that oxyresveratrol supplementation effectively ameliorated obesity-associated symptoms in high-fat diet-fed mice, presumably attributed to mediating critical regulators involved in lipid and glucose homeostasis in liver, visceral fat, and muscle. Full article

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Open AccessArticle Effects of an Encapsulated Fruit and Vegetable Juice Concentrate on Obesity-Induced Systemic Inflammation: A Randomised Controlled Trial

by Evan J. Williams, Katherine J. Baines, Bronwyn S. Berthon and Lisa G. Wood

Nutrients 2017, 9(2), 116; https://doi.org/10.3390/nu9020116

Received: 20 December 2016 / Revised: 23 January 2017 / Accepted: 24 January 2017 / Published: 8 February 2017

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Abstract

Phytochemicals from fruit and vegetables reduce systemic inflammation. This study examined the effects of an encapsulated fruit and vegetable (F&V) juice concentrate on systemic inflammation and other risk factors for chronic disease in overweight and obese adults. A double-blinded, parallel, randomized placebo-controlled trial

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Phytochemicals from fruit and vegetables reduce systemic inflammation. This study examined the effects of an encapsulated fruit and vegetable (F&V) juice concentrate on systemic inflammation and other risk factors for chronic disease in overweight and obese adults. A double-blinded, parallel, randomized placebo-controlled trial was conducted in 56 adults aged ≥40 years with a body mass index (BMI) ≥28 kg/m². Before and after eight weeks daily treatment with six capsules of F&V juice concentrate or placebo, peripheral blood gene expression (microarray, quantitative polymerase chain reaction (qPCR)), plasma tumour necrosis factor (TNF)α (enzyme-linked immunosorbent assay (ELISA)), body composition (Dual-energy X-ray absorptiometry (DEXA)) and lipid profiles were assessed. Following consumption of juice concentrate, total cholesterol, low-density lipoprotein (LDL) cholesterol and plasma TNFα decreased and total lean mass increased, while there was no change in the placebo group. In subjects with high systemic inflammation at baseline (serum C-reactive protein (CRP) ≥3.0 mg/mL) who were supplemented with the F&V juice concentrate (n = 16), these effects were greater, with decreased total cholesterol, LDL cholesterol and plasma TNFα and increased total lean mass; plasma CRP was unchanged by the F&V juice concentrate following both analyses. The expression of several genes involved in lipogenesis, the nuclear factor-κB (NF-κB) and 5′ adenosine monophosphate-activated protein kinase (AMPK) signalling pathways was altered, including phosphomevalonate kinase (PMVK), zinc finger AN1-type containing 5 (ZFAND5) and calcium binding protein 39 (CAB39), respectively. Therefore, F&V juice concentrate improves the metabolic profile, by reducing systemic inflammation and blood lipid profiles and, thus, may be useful in reducing the risk of obesity-induced chronic disease. Full article

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Open AccessArticle Preventive Effects of Drinking Hydrogen-Rich Water on Gingival Oxidative Stress and Alveolar Bone Resorption in Rats Fed a High-Fat Diet

by Toshiki Yoneda, Takaaki Tomofuji, Muneyoshi Kunitomo, Daisuke Ekuni, Koichiro Irie, Tetsuji Azuma, Tatsuya Machida, Hisataka Miyai, Kouhei Fujimori and Manabu Morita

Nutrients 2017, 9(1), 64; https://doi.org/10.3390/nu9010064

Received: 29 November 2016 / Revised: 10 January 2017 / Accepted: 11 January 2017 / Published: 13 January 2017

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Abstract

Obesity induces gingival oxidative stress, which is involved in the progression of alveolar bone resorption. The antioxidant effect of hydrogen-rich water may attenuate gingival oxidative stress and prevent alveolar bone resorption in cases of obesity. We examined whether hydrogen-rich water could suppress gingival

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Obesity induces gingival oxidative stress, which is involved in the progression of alveolar bone resorption. The antioxidant effect of hydrogen-rich water may attenuate gingival oxidative stress and prevent alveolar bone resorption in cases of obesity. We examined whether hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption in obese rats fed a high-fat diet. Male Fischer 344 rats (n = 18) were divided into three groups of six rats each: a control group (fed a regular diet and drinking distilled water) and two experimental groups (fed a high-fat diet and drinking distilled water or hydrogen-rich water). The level of 8-hydroxydeoxyguanosine was determined to evaluate oxidative stress. The bone mineral density of the alveolar bone was analyzed by micro-computerized tomography. Obese rats, induced by a high-fat diet, showed a higher gingival level of 8-hydroxydeoxyguanosine and a lower level of alveolar bone density compared to the control group. Drinking hydrogen-rich water suppressed body weight gain, lowered gingival level of 8-hydroxydeoxyguanosine, and reduced alveolar bone resorption in rats on a high-fat diet. The results indicate that hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption by limiting obesity. Full article

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Open AccessArticle Coenzyme Q10 and Oxidative Stress: Inflammation Status in Hepatocellular Carcinoma Patients after Surgery

by Hsiao-Tien Liu, Shao-Bin Cheng, Yi-Chia Huang, Yin-Tzu Huang and Ping-Ting Lin

Nutrients 2017, 9(1), 29; https://doi.org/10.3390/nu9010029

Received: 25 November 2016 / Revised: 27 December 2016 / Accepted: 28 December 2016 / Published: 4 January 2017

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Abstract

(1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the

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(1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the purpose of this study was to investigate the correlations between the level of coenzyme Q10, oxidative stress, and inflammation in patients with HCC after surgery; (2) Methods: 71 primary HCC patients were recruited. Levels of coenzyme Q10, vitamin E, oxidative stress (malondialdehyde), antioxidant enzymes activity (superoxidase dismutase, catalase, and glutathione peroxidase), and inflammatory markers (high sensitivity C-reactive protein; tumor necrosis factor-α; and interleukin-6) were measured; (3) Results: Patients with HCC had a significantly lower levels of coenzyme Q10 (p = 0.01) and oxidative stress (p < 0.01), and significantly higher levels of antioxidant enzymes activities and inflammation after surgery (p < 0.05). The level of coenzyme Q10 was significantly positively correlated with antioxidant capacity (vitamin E and glutathione peroxidase activity) and negatively correlated with inflammation markers after surgery; (4) Conclusion: Hepatocarcinogenesis is associated with oxidative stress, and coenzyme Q10 may be considered an antioxidant therapy for patients with HCC, particularly those with higher inflammation after surgery. Full article

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Open AccessArticle Impact of Proteins on the Uptake, Distribution, and Excretion of Phenolics in the Human Body

by Richard Draijer, Ferdi A. van Dorsten, Yvonne E. Zebregs, Boudewijn Hollebrands, Sonja Peters, Guus S. Duchateau and Christian H. Grün

Nutrients 2016, 8(12), 814; https://doi.org/10.3390/nu8120814

Received: 4 November 2016 / Revised: 6 December 2016 / Accepted: 8 December 2016 / Published: 15 December 2016

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Abstract

Polyphenols, a complex group of secondary plant metabolites, including flavonoids and phenolic acids, have been studied in depth for their health-related benefits. The activity of polyphenols may, however, be hampered when consumed together with protein-rich food products, due to the interaction between polyphenols

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Polyphenols, a complex group of secondary plant metabolites, including flavonoids and phenolic acids, have been studied in depth for their health-related benefits. The activity of polyphenols may, however, be hampered when consumed together with protein-rich food products, due to the interaction between polyphenols and proteins. To that end we have tested the bioavailability of representatives of a range of polyphenol classes when consumed for five days in different beverage matrices. In a placebo-controlled, randomized, cross-over study, 35 healthy males received either six placebo gelatine capsules consumed with 200 mL of water, six capsules with 800 mg polyphenols derived from red wine and grape extracts, or the same dose of polyphenols incorporated into 200 mL of either pasteurized dairy drink, soy drink (both containing 3.4% proteins) or fruit-flavoured protein-free drink . At the end of the intervention urine and blood was collected and analysed for a broad range of phenolic compounds using Gas Chromatography–Mass Spectrometry (GC-MS), Liquid Chromatography–Multiple Reaction Monitoring–Mass Spectrometry (LC-MRM-MS), and Nuclear Magnetic Resonance (NMR) spectroscopy techniques. The plasma and urine concentrations of the polyphenols identified increased with all formats, including the protein-rich beverages. Compared to capsule ingestion, consumption of polyphenol-rich beverages containing either dairy, soy or no proteins had minor to no effect on the bioavailability and excretion of phenolic compounds in plasma (118% ± 9%) and urine (98% ± 2%). We conclude that intake of polyphenols incorporated in protein-rich drinks does not have a major impact on the bioavailability of a range of different polyphenols and phenolic metabolites. Full article

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Open AccessArticle Regressive Effect of Myricetin on Hepatic Steatosis in Mice Fed a High-Fat Diet

by Shu-Fang Xia, Guo-Wei Le, Peng Wang, Yu-Yu Qiu, Yu-Yu Jiang and Xue Tang

Nutrients 2016, 8(12), 799; https://doi.org/10.3390/nu8120799

Received: 9 October 2016 / Revised: 4 December 2016 / Accepted: 5 December 2016 / Published: 11 December 2016

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Abstract

Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard

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Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet, w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway. Full article

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Open AccessArticle Curcumin and Boswellia serrata Modulate the Glyco-Oxidative Status and Lipo-Oxidation in Master Athletes

by Nino Cristiano Chilelli, Eugenio Ragazzi, Romina Valentini, Chiara Cosma, Stefania Ferraresso, Annunziata Lapolla and Giovanni Sartore

Nutrients 2016, 8(11), 745; https://doi.org/10.3390/nu8110745

Received: 21 October 2016 / Revised: 10 November 2016 / Accepted: 15 November 2016 / Published: 21 November 2016

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Abstract

Background: Chronic intensive exercise is associated with a greater induction of oxidative stress and with an excess of endogenous advanced glycation end-products (AGEs). Curcumin can reduce the accumulation of AGEs in vitro and in animal models. We examined whether supplementation with curcumin and

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Background: Chronic intensive exercise is associated with a greater induction of oxidative stress and with an excess of endogenous advanced glycation end-products (AGEs). Curcumin can reduce the accumulation of AGEs in vitro and in animal models. We examined whether supplementation with curcumin and Boswellia serrata (BSE) gum resin for 3 months could affect plasma levels of markers of oxidative stress, inflammation, and glycation in healthy master cyclists. Methods. Forty-seven healthy male athletes were randomly assigned to Group 1, consisting of 22 subjects given a Mediterranean diet (MD) alone (MD group), and Group 2 consisted of 25 subjects given a MD plus curcumin and BSE (curcumin/BSE group). Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), high-sensitivity c-reactive protein (hs-CRP), total AGE, soluble receptor for AGE (sRAGE), malondialdehyde (MDA), plasma phospholipid fatty acid (PPFA) composition, and non-esterified fatty acids (NEFA) were tested at baseline and after 12 weeks. Results: sRAGE, NEFA, and MDA decreased significantly in both groups, while only the curcumin/BSE group showed a significant decline in total AGE. Only the changes in total AGE and MDA differed significantly between the curcumin/BSE and MD groups. Conclusions. Our data suggest a positive effect of supplementation with curcumin and BSE on glycoxidation and lipid peroxidation in chronically exercising master athletes. Full article

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Open AccessArticle Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

by Davide Grassi, Richard Draijer, Casper Schalkwijk, Giovambattista Desideri, Anatolia D’Angeli, Sandro Francavilla, Theo Mulder and Claudio Ferri

Nutrients 2016, 8(11), 727; https://doi.org/10.3390/nu8110727

Received: 13 September 2016 / Revised: 3 November 2016 / Accepted: 7 November 2016 / Published: 16 November 2016

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Abstract

(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and

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(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001). Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001). Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest. Full article

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Open AccessArticle Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

by Miao Long, Yi Liu, Yu Cao, Nan Wang, Meng Dang and Jianbin He

Nutrients 2016, 8(10), 656; https://doi.org/10.3390/nu8100656

Received: 29 August 2016 / Revised: 5 October 2016 / Accepted: 14 October 2016 / Published: 21 October 2016

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Abstract

Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect

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Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue. Full article

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Open AccessReview Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

by Herson Antonio González-Ponce, Ana Rosa Rincón-Sánchez, Fernando Jaramillo-Juárez and Han Moshage

Nutrients 2018, 10(2), 117; https://doi.org/10.3390/nu10020117

Received: 7 December 2017 / Revised: 14 December 2017 / Accepted: 14 December 2017 / Published: 24 January 2018

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Abstract

Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase

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Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy. Full article

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Open AccessReview Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

by Jorge G. Farías, Víctor M. Molina, Rodrigo A. Carrasco, Andrea B. Zepeda, Elías Figueroa, Pablo Letelier and Rodrigo L. Castillo

Nutrients 2017, 9(9), 966; https://doi.org/10.3390/nu9090966

Received: 4 July 2017 / Revised: 17 August 2017 / Accepted: 18 August 2017 / Published: 1 September 2017

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Abstract

Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes,

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Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability to scavenge these ROS by endogenous antioxidant systems, where ROS overwhelms the antioxidant capacity. Excessive presence of ROS results in irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases related to hypoxia, cardiotoxicity and ischemia–reperfusion. Here, we describe the participation of OS in the pathophysiology of cardiovascular conditions such as myocardial infarction, anthracycline cardiotoxicity and congenital heart disease. This review focuses on the different clinical events where redox factors and OS are related to cardiovascular pathophysiology, giving to support for novel pharmacological therapies such as omega 3 fatty acids, non-selective betablockers and microRNAs. Full article

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Open AccessReview Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity

by María Herranz-López, Mariló Olivares-Vicente, José Antonio Encinar, Enrique Barrajón-Catalán, Antonio Segura-Carretero, Jorge Joven and Vicente Micol

Nutrients 2017, 9(8), 907; https://doi.org/10.3390/nu9080907

Received: 31 July 2017 / Revised: 11 August 2017 / Accepted: 14 August 2017 / Published: 20 August 2017

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Abstract

Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different

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Improper diet can alter gene expression by breaking the energy balance equation and changing metabolic and oxidative stress biomarkers, which can result in the development of obesity-related metabolic disorders. The pleiotropic effects of dietary plant polyphenols are capable of counteracting by modulating different key molecular targets at the cell, as well as through epigenetic modifications. Hibiscus sabdariffa (HS)-derived polyphenols are known to ameliorate various obesity-related conditions. Recent evidence leads to propose the complex nature of the underlying mechanism of action. This multi-targeted mechanism includes the regulation of energy metabolism, oxidative stress and inflammatory pathways, transcription factors, hormones and peptides, digestive enzymes, as well as epigenetic modifications. This article reviews the accumulated evidence on the multiple anti-obesity effects of HS polyphenols in cell and animal models, as well as in humans, and its putative molecular targets. In silico studies reveal the capacity of several HS polyphenols to act as putative ligands for different digestive and metabolic enzymes, which may also deserve further attention. Therefore, a global approach including integrated and networked omics techniques, virtual screening and epigenetic analysis is necessary to fully understand the molecular mechanisms of HS polyphenols and metabolites involved, as well as their possible implications in the design of safe and effective polyphenolic formulations for obesity. Full article

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Open AccessReview The Role of MicroRNAs in the Chemopreventive Activity of Sulforaphane from Cruciferous Vegetables

by Christopher Dacosta and Yongping Bao

Nutrients 2017, 9(8), 902; https://doi.org/10.3390/nu9080902

Received: 13 July 2017 / Revised: 14 August 2017 / Accepted: 15 August 2017 / Published: 19 August 2017

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Abstract

Colorectal cancer is an increasingly significant cause of mortality whose risk is linked to diet and inversely correlated with cruciferous vegetable consumption. This is likely to be partly attributable to the isothiocyanates derived from eating these vegetables, such as sulforaphane, which is extensively

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Colorectal cancer is an increasingly significant cause of mortality whose risk is linked to diet and inversely correlated with cruciferous vegetable consumption. This is likely to be partly attributable to the isothiocyanates derived from eating these vegetables, such as sulforaphane, which is extensively characterised for cytoprotective and tumour-suppressing activities. However, its bioactivities are likely to extend in complexity beyond those currently known; further insight into these bioactivities could aid the development of sulforaphane-based chemopreventive or chemotherapeutic strategies. Evidence suggests that sulforaphane modulates the expression of microRNAs, many of which are known to regulate genes involved at various stages of colorectal carcinogenesis. Based upon existing knowledge, there exist many plausible mechanisms by which sulforaphane may regulate microRNAs. Thus, there is a strong case for the further investigation of the roles of microRNAs in the anti-cancer effects of sulforaphane. There are several different types of approach to the wide-scale profiling of microRNA differential expression. Array-based methods may involve the use of RT-qPCR or complementary hybridisation probe chips, and tend to be relatively fast and economical. Cloning and deep sequencing approaches are more expensive and labour-intensive, but are worth considering where viable, for their greater sensitivity and ability to detect novel microRNAs. Full article

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Open AccessReview Food-Derived Antioxidant Polysaccharides and Their Pharmacological Potential in Neurodegenerative Diseases

by Haifeng Li, Fei Ding, Lingyun Xiao, Ruona Shi, Hongyu Wang, Wenjing Han and Zebo Huang

Nutrients 2017, 9(7), 778; https://doi.org/10.3390/nu9070778

Received: 31 May 2017 / Revised: 10 July 2017 / Accepted: 13 July 2017 / Published: 19 July 2017

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Abstract

Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over

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Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities. Full article

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Open AccessReview Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress

by Mustapha Umar Imam, Shenshen Zhang, Jifei Ma, Hao Wang and Fudi Wang

Nutrients 2017, 9(7), 671; https://doi.org/10.3390/nu9070671

Received: 4 June 2017 / Revised: 20 June 2017 / Accepted: 22 June 2017 / Published: 28 June 2017

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Abstract

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants

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Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions. Full article

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Open AccessReview Dietary Sources and Bioactivities of Melatonin

by Xiao Meng, Ya Li, Sha Li, Yue Zhou, Ren-You Gan, Dong-Ping Xu and Hua-Bin Li

Nutrients 2017, 9(4), 367; https://doi.org/10.3390/nu9040367

Received: 21 January 2017 / Revised: 14 March 2017 / Accepted: 31 March 2017 / Published: 7 April 2017

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Abstract

Insomnia is a serious worldwide health threat, affecting nearly one third of the general population. Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. During the last decades, melatonin has been widely identified

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Insomnia is a serious worldwide health threat, affecting nearly one third of the general population. Melatonin has been reported to improve sleep efficiency and it was found that eating melatonin-rich foods could assist sleep. During the last decades, melatonin has been widely identified and qualified in various foods from fungi to animals and plants. Eggs and fish are higher melatonin-containing food groups in animal foods, whereas in plant foods, nuts are with the highest content of melatonin. Some kinds of mushrooms, cereals and germinated legumes or seeds are also good dietary sources of melatonin. It has been proved that the melatonin concentration in human serum could significantly increase after the consumption of melatonin containing food. Furthermore, studies show that melatonin exhibits many bioactivities, such as antioxidant activity, anti-inflammatory characteristics, boosting immunity, anticancer activity, cardiovascular protection, anti-diabetic, anti-obese, neuroprotective and anti-aging activity. This review summaries the dietary sources and bioactivities of melatonin, with special attention paid to the mechanisms of action. Full article

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Open AccessReview Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

by Masutaka Furue, Hiroshi Uchi, Chikage Mitoma, Akiko Hashimoto-Hachiya, Takahito Chiba, Takamichi Ito, Takeshi Nakahara and Gaku Tsuji

Nutrients 2017, 9(3), 223; https://doi.org/10.3390/nu9030223

Received: 1 February 2017 / Revised: 24 February 2017 / Accepted: 28 February 2017 / Published: 3 March 2017

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Abstract

Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are

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Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation. Full article

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Open AccessReview Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

by Virginie Lam, Mark Hackett and Ryusuke Takechi

Nutrients 2016, 8(12), 828; https://doi.org/10.3390/nu8120828

Received: 15 November 2016 / Revised: 16 December 2016 / Accepted: 16 December 2016 / Published: 20 December 2016

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Abstract

A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects

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A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB) is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms. Full article

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Open AccessReview Fish Consumption and Age-Related Macular Degeneration Incidence: A Meta-Analysis and Systematic Review of Prospective Cohort Studies

by Wei Zhu, Yan Wu, Yi-Fang Meng, Qian Xing, Jian-Jun Tao and Jiong Lu

Nutrients 2016, 8(11), 743; https://doi.org/10.3390/nu8110743

Received: 22 August 2016 / Revised: 2 October 2016 / Accepted: 11 November 2016 / Published: 22 November 2016

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Abstract

The association between fish consumption and risk of age-related macular degeneration (AMD) is still unclear. The aim of the current meta-analysis and systematic review was to quantitatively evaluate findings from observational studies on fish consumption and the risk of AMD. Relevant studies were

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The association between fish consumption and risk of age-related macular degeneration (AMD) is still unclear. The aim of the current meta-analysis and systematic review was to quantitatively evaluate findings from observational studies on fish consumption and the risk of AMD. Relevant studies were identified by searching electronic databases (Medline and EMBASE) and reviewing the reference lists of relevant articles up to August, 2016. Prospective cohort studies that reported relative risks (RRs) and 95% confidence intervals (CIs) for the link between fish consumption and risk of AMD were included. A total of 4202 cases with 128,988 individuals from eight cohort studies were identified in the current meta-analysis. The meta-analyzed RR was 0.76 (95% CI, 0.65–0.90) when any AMD was considered. Subgroup analyses by AMD stages showed that fish consumption would reduce the risk of both early (RR, 0.83; 95% CI, 0.72–0.96) and late (RR; 0.76; 95% CI, 0.60–0.97) AMD. When stratified by the follow-up duration, fish consumption was a protective factor of AMD in both over 10 years (n = 5; RR, 0.81; 95% CI, 0.67–0.97) and less than 10 years (n = 3; RR, 0.70; 95% CI, 0.51 to 0.97) follow-up duration. Stratified analyses by fish type demonstrated that dark meat fish (RR, 0.68, 95% CI, 0.46–0.99), especially tuna fish (RR, 0.58; 95% CI, 95% CI, 0.47–0.71) intake was associated with reduced AMD risk. Evidence of a linear association between dose of fish consumption and risk of AMD was demonstrated. The results of this meta-analysis demonstrated that fish consumption can reduce AMD risk. Advanced, well-designed, randomized clinical trials are required in order to validate the conclusions in this study. Full article

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