Bioavailable Phenolic Compounds from Olive Pomace Present Anti-Neuroinflammatory Potential on Microglia Cells.

The neuroinflammatory process is considered one of the main characteristics of central nervous system diseases, where a pro-inflammatory response results in oxidative stress through the generation of reactive oxygen and nitrogen species (ROS and RNS). Olive (Olea europaea L.) pomace is a by-product of olive oil production that is rich in phenolic compounds (PCs), known for their antioxidant and anti-inflammatory properties. This work looked at the antioxidant and anti-neuroinflammatory effects of the bioavailable PC from olive pomace in cell-free models and microglia cells. The bioavailable PC of olive pomace was obtained through the process of in vitro gastrointestinal digestion of fractionated olive pomace (OPF, particles size < 2 mm) and micronized olive pomace (OPM, particles size < 20 µm). The profile of the PC that is present in the bioavailable fraction as well as its in vitro antioxidant capacity were determined. The anti-neuroinflammatory capacity of the bioavailable PC from olive pomace (0.03-3 mg L-1) was evaluated in BV-2 cells activated by lipopolysaccharide (LPS) for 24 h. The total bioavailable PC concentration and antioxidant activity against peroxyl radical were higher in the OPM than those observed in the OPF sample. The activation of BV-2 cells by LPS resulted in increased levels of ROS and nitric oxide (NO). The bioavailable PCs from both OPF and OPM, at their lowest concentrations, were able to reduce the ROS generation in activated BV-2 cells. In contrast, the highest PC concentration of OPF and OPM was able to reduce the NO levels in activated microglial cells. Our results demonstrate that bioavailable PCs from olive pomace can act as anti-neuroinflammatory agents in vitro, independent of particle size. Moreover, studies approaching ways to increase the bioavailability of PCs from olive pomace, as well as any possible toxic effects, are needed before a final statement on its nutritional use is made.

Antiproliferative Effect of Colonic Fermented Phenolic Compounds from Jaboticaba (Myrciaria trunciflora) Fruit Peel in a 3D Cell Model of Colorectal Cancer.

Jaboticaba is a Brazilian native berry described as a rich source of phenolic compounds (PC) with health promoting effects. PC from jaboticaba peel powder (JPP) have low intestinal bio-accessibility and are catabolized by gut microbiota. However, the biological implication of PC-derived metabolites produced during JPP digestion remains unclear. This study aimed to evaluate the antiproliferative effects of colonic fermented JPP (FJPP) in a 3D model of colorectal cancer (CRC) composed by HT29 spheroids. JPP samples fermented with human feces during 0, 2, 8, 24 or 48 h were incubated (10,000 µg mL-1) with spheroids, and cell viability was assessed after 72 h. Chemometric analyses (cluster and principal component analyses) were used to identify the main compounds responsible for the bioactive effect. The antiproliferative effect of FJPP in the CRC 3D model was increased between 8 h and 24 h of incubation, and this effect was associated with HHDP-digalloylglucose isomer and dihydroxyphenyl-γ-valerolactone. At 48 h of fermentation, the antiproliferative effect of FJPP was negligible, indicating that the presence of urolithins did not improve the bioactivity of JPP. These findings provide relevant knowledge on the role of colonic microbiota fermentation to generate active phenolic metabolites from JPP with positive impact on CRC.

New insights into the phenolic compounds and antioxidant capacity of feijoa and cherry fruits cultivated in Brazil.

Acca sellowiana (feijoa) and Eugenia involucrata (cherry) are fruits species of Brazilian biodiversity (Myrtaceae family). In this study, a sampling process was used with three different harvesting sites. The composition of phenolic compounds of these fruits was determined by HPLC-DAD-MS/MS. Moreover, the antioxidant capacity of hydroethanolic extracts against hydrogen peroxide (H2O2), hydroxyl (OH), peroxyl (ROO-) and ABTS radicals was evaluated. Thirty and twenty-seven phenolic compounds were identified in feijoa and cherry, respectively. The major phenolic compounds found were pedunculagin isomer (5040.87, 3443.66 and 1324.95 µg·g-1) in feijoa and procyanidin (1406.54, 1888.00 and 1380.64 µg·g-1) in cherry. Hydroethanolic extract of these fruits was a potent scavenger of free radicals and excellent source of phenolic compounds. In hydroethanolic extracts of feijoa, the phenolic content increased by around 50%, while in the cherry the content was similar to that found in the fruit. For ORAC method, sample 2 of feijoa and cherry showed values of 383 and 126 µM·TE·g-1, respectively, featuring the highest antioxidant capacity. This study is the first to report the identification of castalagin, catechin and epicatechin in feijoa, and rutin in cherry. Besides, the health benefits, these fruits can contribute to biodiversity conservation.

Ochratoxin A presence in Cabernet Sauvignon wine changes antioxidant activity in vitro and oxidative stress markers in vivo.

Ochratoxin A (OTA) is a mycotoxin found in grape products and oxidative stress has been reported as an important mechanism involved in its toxicity, classified as possible carcinogenic to humans. Conversely, phenolics are known bioactive compounds in grapes and display great antioxidant properties. However, the biological effects of the concomitant presence of phenolic compounds and OTA remains unclear. The aim of this study was to evaluate, for the first time, the effect of OTA presence in Cabernet Sauvignon wine on antioxidant activity in vitro and on oxidative stress markers in vivo. In addition, the phenolic composition of wine was evaluated by LC-DAD-MS/MS. In vitro assays were based on spectrophotometric methods, while in vivo assays were performed evaluating oxidative stress markers in the nematode Caenorhabditis elegans, an alternative model to animal testing. A total of 23 phenolic compounds were identified in the Cabernet sauvignon red wine, including the anthocyanins delphinidin-3-O-glicoside and malvidin-3-O-glicoside, the flavonol quercetin-3-O-glucuronide and the phenolic acids caffeic, verbascoside and caftaric. Trans-resveratrol and trans-piceid were the only stilbenes found in the samples. OTA presence in the red wine was accompanied by reduction in GSH content and increase in hydroxyl radical generation in vitro. The presence of OTA in wine also increased lipoperoxidation and induced overexpression of the antioxidant enzymes superoxide dismutase and catalase in vivo. This study demonstrates that OTA presence in red wine can reduce its antioxidant potential in vitro and induces oxidative stress in vivo, without affecting the phenolic compounds levels in the samples. Thus, this work provides insights into the negative effects of the presence of OTA in wine, not only by its known toxicity, but also by prejudicing the antioxidant potential of wine. It is important to be aware of these effects when developing a complete description of OTA toxicity in humans.

Effect of Aspergillus carbonarius on ochratoxin a levels, volatile profile and antioxidant activity of the grapes and respective wines.

Aspergillus carbonarius can produce a possibly carcinogenic mycotoxin named ochratoxin A (OTA). The metabolism of this fungus can also impact grape and wine quality as it influences the volatile and phenolic profiles, which are related to aroma and antioxidant activity, respectively. The objective of this study was to evaluate the effect of A. carbonarius on OTA levels and for the first time on volatile profile and antioxidant activity of grapes and their respective wines. Cabernet Sauvignon (CS, red) grapes presented higher susceptibility to A. carbonarius than Moscato Italico (MI, white) grapes and OTA levels in their respective musts were in accordance with this same trend. However, vinification of red grapes resulted in 67% reduction of OTA, while the reduction observed with white wines was 45%. The presence of acids (hexanoic, octanoic, nonanoic and decanoic, fatty odor) was found to be an indicative of the fungus incidence in grapes. These acids were precursors of esters that might impart negative aroma (methyl nonanoate and isoamyl octanoate, fatty odor) or provide desirable fruity characteristics (ethyl hexanoate, ethyl octanoate and methyl octanoate) for wine. In addition, terpenes were detected only in wines produced with grapes (CS and MI) inoculated with A. carbonarius. The presence of A. carbonarius increased the antioxidant activity of CS grapes. For MI grapes and both wines (CS and MI) no differences were verified in the antioxidant activity of the samples affected or not affected by this fungus. Although A. carbonarius occurrence has shown no influence on the antioxidant activity of wines, it produced OTA and has negatively influenced the wine odor profile, due to the production of some volatiles that impart a deleterious effect on wine aroma.

Efeito da ocratoxina A em suco de uva tinto sobre sobrevivência e geração de EROs em Caenoaerbiditis elegans / Effects of ochratoxin A in red grape juice on survival rate and ROs generation in Caenoaerbiditis elegans

O consumo do suco de uva vem crescendo ao longo dos anos em função das suas propriedades funcionais. No entanto, este produto não está livre de contaminantes como a ocratoxina A (OTA). O presente trabalho teve por objetivo avaliar o efeito da presença de OTA em suco de uva Concord sobre geração de espécies reativas de oxigênio (EROs) e taxa de sobrevivência em Caenoarbiditis elegans. Os vermes foram expostos por 30 minutos ao suco na presença de OTA (0, 1, 2 e 4 µg∙L-1). O suco em presença de OTA não afetou a sobrevivência do C. Elegans. A adição de suco livre de OTA reduziu a sobrevivência dos nematoides, embora não tenha influenciado a geração de EROs. Contudo o suco com a concentração mais elevada de OTA reduziu a geração de EROs. Assim, são necessários maiores estudos para entender os mecanismos de toxicidade da OTA neste modelo vivo.

Composição fenólica e perfil antioxidante do suco de uva Concord / Phenolic composition and antioxidant profile of Concord grape juice

O suco de uva apresenta na constituição química uma diversidade de substâncias com ações benéficas, especialmente compostos fenólicos. O trabalho teve como objetivo analisar a composição fenólica e a capacidade antioxidante in vitro do suco de uva Concord. A atividade antioxidante foi avaliada pelos métodos de oxidação da GSH, geração do radical ABTS e ensaio da desoxirribose. A análise da composição fenólica foi realizada utilizando HPLC-DAD-MS. O suco reduziu a geração dos radicais ABTS e hidroxil bem como elevou o conteúdo de GSH. Os compostos fenólicos majoritários no suco de uva Concord foram antocianinas, ácidos fenólicos e flavonols. Os resultados obtidos demonstram o potencial antioxidante do suco da variedade Concord, possivelmente associado à sua composição fenólica.

Bioactive compounds and protective effect of red and black rice brans extracts in human neuron-like cells (SH-SY5Y).

Rice bran is obtained from the rice polishing process, and this by-product contains many bioactive compounds. In this study, the composition of phenolic compounds from red and black rice brans was determined by HPLC-DAD-MS. Additionally, the neuroprotective ability of these brans in SH-SY5Y cells insulted with hydrogen peroxide (H2O2) was evaluated. The phenolic constituents of rice bran were separated into hydrophilic and pellet fractions. The major phenolic compound in both samples was ferulic acid. Cyanidin 3-glucoside was the main anthocyanin in black rice bran. The hydrophilic and pellet fractions showed a protective effect (38-94%) on SH-SY5Y cells insulted by H2O2 in DCFH-DA assay. No extract showed cytotoxicity in the SRB assay. These results suggest a neuroprotective effect of red and black rice brans extracts due to their high antioxidant capacity, along with the absence of cytotoxicity. Thus, they may potentially be used as sources of bioactive compounds.

The Hepatoprotective Effect of Jaboticaba Peel Powder in a Rat Model of Type 2 Diabetes Mellitus Involves the Modulation of Thiol/Disulfide Redox State through the Upregulation of Glutathione Synthesis.

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzyme δ-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

Microcystin-LR exposure induces oxidative damage in Caenorhabditis elegans: Protective effect of lutein extracted from marigold flowers.

Microcystin-LR (MIC-LR) is a hepatotoxin, with toxicity mechanisms linked to oxidative stress. Besides, neurotoxic effects of MIC-LR have recently been described. Herein, we evaluated the effects of environmentally important concentrations of MIC-LR (1, 10, 100, 250, and 500 µg/L) on oxidative stress markers and the survival rate of the nematode Caenorhabditis elegans (C. elegans). In addition, a possible protective effect of the carotenoid lutein (LUT) extracted from marigold flowers against MIC-LR toxicity was investigated. Higher concentrations (250 and 500 µg/L) of MIC-LR induced the generation of reactive oxygen species (ROS) and resulted in a survival loss in C elegans. Meanwhile, all MIC-LR concentrations caused an increase in the superoxide dismutase (SOD) expression, while catalase (CAT) expression was only affected at 500 µg/L. The carotenoid LUT prevented the ROS generation, impairment in the CAT expression, and the survival loss induced by MIC-LR in C. elegans. Our results confirm the toxicity of MIC-LR even in a liver-lacking invertebrate and the involvement of oxidative events in this response. Additionally, LUT appears to be able to mitigate the MIC-LR toxic effects.

Hydroethanolic extracts from different genotypes of açaí (Euterpe oleracea) presented antioxidant potential and protected human neuron-like cells (SH-SY5Y).

Fruit breeding programs have resulted in bioactive compounds increase and health effects. Thus, this study aimed to evaluate the antioxidant activity and neuroprotective effects of the hydroethanolic extracts from six açaí (Euterpe oleracea) genotypes using ABTS, deoxyribose, and glutathione oxidation assays, as well as, SH-SY5Y cells insulted with H2O2. L22P13 genotype showed the highest total content of anthocyanins, while L06P13 showed a high content of total carotenoids. However, the genotypes showed no difference in the antioxidant activity by ABTS and deoxyribose assays. The hydroethanolic extracts from different genotypes of açaí showed a protective effect (13-62%) on SH-SY5Y cells insulted by H2O2 at a concentration of 50µg/mL by DCFH-DA assay. Except L04P16, no genotypes showed cytotoxicity in the SRB assay. These results indicate that açaí genotypes have antioxidant effect against reactive species generated in SH-SY5Y cells, suggesting a neuroprotective effect of the hydroethanolic extracts from these fruits.

Imbalance in superoxide dismutase/thioredoxin reductase activities in hypercholesterolemic subjects: relationship with low density lipoprotein oxidation.

BACKGROUND: There is a relationship among hypercholesterolemia, oxidative stress and inflammation in the atherogenesis. Thus, the objective of the present study was to assess paraoxonase (PON1), superoxide dismutase (SOD) and thioredoxin reductase (TrxR-1) activities and their relationship with lipids, oxidative stress and inflammation in subjects with different low density lipoprotein-cholesterol (LDL) levels. METHODS: Serum lipids, highly sensitive C-reactive protein (hs-CRP), lipid and protein oxidation, oxidized LDL (LDLox) and LDLox autoantibodies (LDLoxAB) levels and enzymes activities were measured in a total of 116 subjects that were divided into the following groups according to their LDL levels: low-LDL group (LDL < 100 mg/dL, n = 23), intermediate-LDL group (LDL 100-160 mg/dL, n = 50) and high-LDL group (LDL > 160 mg/dL, n = 43). RESULTS: The LDLox and hs-CRP levels increased in the high-LDL group (2.7- and 3.7- fold, respectively), whereas the intermediate and high-LDL groups had higher LDLoxAB (2.2- and 3.1-fold) when compared to low-LDL group (p < 0.05). Similarly, SOD activity, the atherogenic index (AI) and protein oxidation were also higher in the intermediate (1.3-, 1.3- and 1.2-fold) and high-LDL (1.6-, 2.3- and 1.6-fold) groups when compared to the low-LDL group (p < 0.05). Lipid oxidation and SOD/TrxR-1 ratio increased only in the high-LDL group (1.3- and 1.6-fold) when compared to the low-LDL group (p < 0.05). The SOD/TrxR-1 ratio was positively correlated to TBARS (r = 0.23, p < 0.05), LDLox (r = 0.18, p < 0.05), LDLoxAB (r = 0.21, p < 0.05), LDL (r = 0.19, p < 0.05) and AI (r = 0.22, p < 0.05). PON1 and TrxR-1 activities were similar among groups. CONCLUSIONS: Some oxidative events initiate when LDL levels are clinically acceptable. Moreover, hypercholesterolemic patients have an imbalance in SOD and TrxR-1 activities that is positively associated to LDL oxidation.

Dimethyl sulfoxide and ebselen prevent convulsions induced by 5-aminolevulinic acid.

We investigated whether intrastriatal (i.s.) administration of 5-aminolevulinic acid (ALA) induces oxidative damage and whether behavioral alterations induced by i.s. administration of ALA could be affected by antioxidants. Unilateral injection of ALA (6 micromol/striatum) increased (approximately 30%) thiobarbituric acid-reactive substances (TBARS), but did not affect striatal content of total thiol groups. ALA-induced body asymmetry was not prevented by pretreatment with ascorbic acid (100 mg/kg, s.c.), dimethyl sulfoxide (DMSO, 0.5 microl/striatum, i.s.) or ebselen (10 nmol/striatum, i.s.). ALA-induced convulsions were not prevented by ascorbic acid, but were partially prevented by DMSO and completely prevented by ebselen. Ebselen completely prevented the increase of striatal TBARS induced by ALA. Results obtained suggest the involvement of reactive species in ALA-induced convulsions and may be of value in understanding the physiopathology of neurological dysfunctions associated to ALA overload.