100% Orange Juice Consumption is Associated with Socioeconomic Status, Improved Nutrient Adequacy, and Higher Bioactive Compounds Intake: Results from Brazilian National Dietary Survey 2017-2018.

OBJECTIVE: The consumption of 100% orange juice (OJ) has been associated with nutrient adequacy and better diet quality. To date, there are few analyses exploring 100% OJ consumption patterns across populations, with no data from Brazil. We aimed to explore the associations between 100% OJ consumption, sociodemographic factors, and nutrient intake in a representative sample of the Brazilian general population aged 10 years or older. METHODS: Data were obtained from the National Dietary Survey 2017-2018, a cross-sectional study including data on individual food intake of 46,164 subjects aged ≥10 years collected using two 24-h dietary recalls. RESULTS: 100% OJ was consumed by 11% of the population, with a mean intake of 43.0 ml/d. Males were more frequent consumers compared to females, and the percentage of consumers increased with education and income. 100% OJ consumption was associated with higher intakes of energy, vitamin C, folate, calcium, magnesium, potassium, polyphenols, and carotenoids. There is no significant difference in fiber intake between consumers and non-consumers. 100% OJ consumers had a higher percentage of the population meeting the Estimated Average Requirement for vitamin A, vitamin C, vitamin D, folate, calcium, and magnesium. CONCLUSION: Our results suggest that 100% OJ could be a component of a healthy diet, helping individuals to achieve nutrient recommendations.

HDAC specificity and kinase off-targeting by purine-benzohydroxamate anti-hematological tumor agents.

A series of hybrid inhibitors, combining pharmacophores of known kinase inhibitors bearing anilino-purines (ruxolitinib, ibrutinib) and benzohydroxamate HDAC inhibitors (nexturastat A), were generated in the present study. The compounds have been synthesized and tested against solid and hematological tumor cell lines. Compounds 4d-f were the most promising in cytotoxicity assays (IC50 ≤ 50 nM) vs. hematological cells and displayed moderate activity in solid tumor models (EC50 = 9.3-21.7 µM). Compound 4d potently inhibited multiple kinase targets of interest for anticancer effects, including JAK2, JAK3, HDAC1, and HDAC6. Molecular dynamics simulations showed that 4d has stable interactions with HDAC and members of the JAK family, with differences in the hinge binding energy conferring selectivity for JAK3 and JAK2 over JAK1. The kinase inhibition profile of compounds 4d-f allows selective cytotoxicity, with minimal effects on non-tumorigenic cells. Moreover, these compounds have favorable pharmacokinetic profiles, with high stability in human liver microsomes (e.g., see t1/2: >120 min for 4f), low intrinsic clearance, and lack of significant inhibition of four major CYP450 isoforms.

1,3-Diphenylureido hydroxamate as a promising scaffold for generation of potent antimalarial histone deacetylase inhibitors.

We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a-d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro, mechanistic studies demonstrated target activity for PfHDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c, 7c, and 8c, identified as the most active in phenotypic assays and PfHDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of PfHDAC1, with an IC50 value of 0.74 µM in the phenotypic screening on Pf3D7 and 0.8 µM against multidrug-resistant PfDd2 parasites. Despite its potent inhibition of PfHDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with PfHDAC1 and that this compound series could bind as well as in HsHDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs.

Bioactive compounds intake in the Brazilian population: Trends and determinants of socioeconomic inequalities between 2008 and 2018.

OBJECTIVE: The present study aims at evaluating trends and determinants of socioeconomic inequalities in consumption of bioactive compounds in representative sample of the Brazilian population the period from 2008-2009 to 2017-2018. METHODS: Data from two cross-sectional population-based surveys were analyzed in the study, using descriptive analysis and estimation of inequalities in consumption. Trends in polyphenol and carotenoid intake were estimated using food consumption data from National Dietary Survey (NDS) 2008-2009 (n = 34,003) and 2017-2018 (n = 46,164). Evolution and determinants of inequalities in bioactive compounds intake were identified using analysis of inequality based on concentration index. RESULTS: Consumption of total polyphenols, phenolic acids, flavonoids and carotenoid classes (except for zeaxanthin) was significantly associated with per capita income after adjustment for potential confounders, being higher income associated with higher intake of bioactive compounds. Disaggregation of inequalities showed that education was the main factor associated with consumption of flavonoids, other polyphenols and ß-cryptoxanthin in 2008-2009; whilst income was the main barrier to intake of polyphenols and carotenoids in 2017-2018. CONCLUSION: Income level and educational attainment have been important determinants to inequalities in bioactive compounds intake in the Brazilian population throughout the period of analysis, being higher intake of bioactive compounds-rich foods and beverages associated with higher income.

Bioactive Compounds Intake of the Brazilian Population According to Geographic Region.

Studies have been conducted in order to estimate bioactive compound consumption across populations, with substantial disparities according to the origin of the cohort examined. In this sense, Brazil is a continental country with marked differences in food plant availability across geographic regions. We aimed to estimate the bioactive compound intake according to Brazilian geographic region, as well as to determine the major contributors. Data were obtained from the National Dietary Survey 2017-2018, a cross-sectional population-based study including data on the individual food intake of 46,164 subjects aged ≥10 years. The consumption of polyphenols (total and classes) was significantly higher in the South compared with other regions (p = 0.0001). Total carotenoid intake was higher in the Midwest, followed by the Southeast (p = 0.0001). Tea was the main supplier of total polyphenol intake in the South, whereas coffee contributed the most to total polyphenol intake in other Brazilian regions. Açaí, caja juice, mango and corn were important suppliers of carotenoid intake in the North and Northeast. Bioactive compound intake presented variations according to Brazilian region, and individuals living in the South, Midwest and Southeast may experience higher bioactive-dense diets. We highlight the potential of many food plants for sustained explorations to the development of marketable products, possibly increasing the bioactive compound intake.

Estimated polyphenol intake and major food sources of the Brazilian population: changes between 2008-2009 and 2017-2018.

Assessing the dietary intake of polyphenols and their major food sources is the first step towards documenting the associations with health outcomes. Considering recent changes in dietary patterns of the Brazilian population, continuous monitoring of polyphenol intake is important. Thus, the present study was conducted to estimate the polyphenol intake and major food sources in the diet of the Brazilian population using data from the most recent National Dietary Survey (NDS, 2017-2018), to characterise the intake changes according to demographic characteristics and to compare the intake over the past decade in Brazil. Data from two cross-sectional population-based surveys were analyzed in the study. Trends in polyphenol intake and major food sources were estimated using food consumption data from NDS 2008-2009 (n 34 003) and 2017-2018 (n 46 164). The median (25-75th percentiles) of energy-adjusted polyphenol intake in 2017-2018 was 216·3 mg (125·3-495·2 mg) per 1000 kcal/d (4184 kJ/d), representing an increase of 12·3 mg/d from 2008-2009. However, unadjusted polyphenol intakes were similar between the surveys (medians: 364·3 mg/d in 2008-2009 and 366·9 mg/d in 2017-2018). The main food sources of total and polyphenol intake classes presented some variations between 2008-2009 and 2017-2018, with greater contribution of beans preparations, salads and tea to polyphenol intake, and decrease of orange contribution. Our study provided an updated information on polyphenol intake and its major food sources. The median intake remains lower than the reported by other populations. Furthermore, the results may contribute to future studies investigating temporal trends in polyphenol intake and disease risk.

Ingestion of orange juice prevents hyperglycemia and increases plasma miR-375 expression.

BACKGROUND & AIMS: The intake of high-fat, high-carbohydrate (HFHC) meals is associated with an increased risk of type 2 diabetes. There is evidence that the association of orange juice to a HFHC meal can modulate the expression of microRNAs (miRNAs) linked to pancreatic ß-cell function such as miR-375. We evaluated the effect of a commercial orange juice intake with HFHC meal on plasma miRNAs expression in twelve healthy subjects in a crossover design study. METHODS: Subjects ingested water, orange juice, or an isocaloric beverage along with a 1037 kcal HFHC meal. Blood glucose and miRNAs were evaluated at baseline and 1, 3, and 5 h after the intake. RESULTS: The area under the curve (AUC) for glycemia after ingestion of HFHC + orange juice did not differ from ingestion of HPHC + glucose or HFHC + water. However, the AUC was higher in HFHC meal + glucose compared to HFHC meal + water (p = 0.034). Glucose and insulin concentrations were significantly higher in HFHC meal + glucose group after 1 h, when compared with other groups and times (p < 0.001). There was an increase in plasma miR-375 expression after 3 h of ingestion of HFHC + orange juice versus water (p = 0.026), and a decrease in plasma miR-205-5p expression after HFHC meal + glucose versus water (p = 0.023). CONCLUSIONS: A single HFHC meal + orange juice modulated plasma miR-375 expression, which is a biomarker of pancreatic ß-cell function, and contributed to preventing hyperglycemia.

Assessment of dietary intake of bioactive food compounds according to income level in the Brazilian population.

There is an inverse association between bioactive compounds intake and disease risk. The knowledge of its consumption according to socio-economic strata is important, which allows identification of potential intervention targets. Thus, we aimed to investigate bioactive compounds intake according to income level in Brazilian population. Data were obtained from the Brazilian Household Budget Survey, a cross-sectional survey which included data on individual food intake of 34,003 subjects aged 10 years and over collected using two 24-h dietary records. Polyphenol and carotenoid content of foods was identified using published databases. Total polyphenol and carotenoid intake were determined according to per capita income, as well as main food sources. Total polyphenols and flavonoids intake increased with income level, and subjects with lower income showed higher phenolic acids intake than individuals in highest income (p = 0.0001). Total carotenoids and classes intake (with exception to ß-cryptoxanthin and zeaxanthin) were higher among subjects in highest income quartile, compared to the lowest quartile (p = 0.0001). Coffee was major source to total polyphenols and phenolic acids intake, and orange juice was main flavonoid provider in individuals from all income levels. In the upper income quartile, total carotenoid was supplied mainly by tomato and kale, and fruits had important contribution to carotenoid intake in the lowest income quartile. There is important influence of income level on diet quality regarding intake of foods with bioactive compounds, and individuals with lower income may experience lower quality diets due to less availability of foods with bioactive compounds.

Purple grumixama anthocyanins (Eugenia brasiliensis Lam.) attenuate obesity and insulin resistance in high-fat diet mice.

Some polyphenols have been reported to modulate the expression of several genes related to lipid metabolism and insulin signaling, ameliorating metabolic disorders. We investigated the potential for the polyphenols of two varieties of grumixama, the purple fruit rich in anthocyanins and the yellow fruit, both also rich in ellagitannins, to attenuate obesity-associated metabolic disorders. Mice were fed a high fat and high sucrose diet, supplemented daily with yellow and purple extracts (200 mg per kg of body weight) for eight weeks. Purple grumixama supplementation was found to decrease body weight gain, improve insulin sensitivity and glucose-induced hyperinsulinemia, and reduce hepatic triglyceride accumulation. A decrease in intrahepatic lipids in mice treated with the purple grumixama extract was associated with lipid metabolism modulation by the PPAR signaling pathway. LPL, ApoE, and LDLr were found to be down-regulated, while Acox1 and ApoB were found to be upregulated. Some of these genes were also modulated by the yellow extract. In addition, both extracts decreased oGTT and plasma LPS. The results were associated with the presence of phenolic acids and urolithins. In conclusion, most likely the anthocyanins from the purple grumixama phenolic extract is responsible for reducing obesity and insulin resistance.

Estimated dietary polyphenol intake and major food sources of the Brazilian population.

Epidemiological studies have suggested an inverse association between polyphenol intake and the risk of chronic diseases. However, the lack of comprehensive data on population-level intakes, especially in Latin American countries, has limited research on this topic. We aimed to estimate total and individual polyphenol intakes and determine the major dietary contributors in a representative sample of the Brazilian population. Data were obtained from the Brazilian Household Budget Survey, a cross-sectional survey which included data on individual food intake of 34 003 subjects aged 10 years and over collected using two 24-h dietary records. Polyphenol content of foods was identified using the Phenol-Explorer database and Brazilian Food Composition Database. Total and individual polyphenol intake was calculated, as well as the intake distribution by socio-demographic factors. The median and 25-75th percentiles of polyphenol intake were 364·3 and 200·9-1008 mg/d, respectively. After energy adjustment, the median and 25-75th percentiles of polyphenol intake were 204 and 111·4-542·1 mg/1000 kcal/d (4184 kJ/d), respectively. Non-alcoholic beverages and fruits were the major polyphenol suppliers, and coffee and orange juice the main individual food contributors to polyphenol intake. The individual compounds most consumed were isomers of chlorogenic acid (5-caffeoylquinic acid, 4-caffeoylquinic acid, 3-caffeoylquinic acid), naringenin and hesperetin. The present study provides, for the first time, data on dietary intake of total and individual polyphenols by the Brazilian population and illustrates the low quality of their diet. These results will facilitate the study of associations between polyphenol class intake and health outcomes, and will also be useful for future dietary intake recommendations.

Citrus flavanone metabolites protect pancreatic-ß cells under oxidative stress induced by cholesterol.

Cholesterol is one of the triggers of oxidative stress in the pancreatic-ß cell, generating high levels of reactive oxygen species, which leads to impairment of insulin synthesis and secretion. Bioactive compounds, such as citrus flavanones, which possess anti-inflammatory and antioxidant activities, could reduce oxidative stress in ß-cells and improve their function. We describe for the first time the protective effects of the phase-II flavanone metabolites [naringenin 7-O-glucuronide, hesperetin 3'-O-glucuronide, and hesperetin 7-O-glucuronide], and two flavanones-catabolites derived from gut microbiota metabolism [hippuric acid and 3-(4-hydroxyphenyl)propionic acid], on pancreatic ß-cell line MIN6 under oxidative stress, at physiologically relevant concentration. Cholesterol reduced cell viability in a dose and time-dependent manner, with an improvement in the presence of the metabolites. Moreover, flavanone metabolites attenuated oxidative stress by reducing levels of lipid peroxides, superoxide anions, and hydrogen peroxide. In response to the reduction of reactive oxygen species, a decrease in superoxide dismutase and glutathione peroxidase activities was observed; these activities were elevated by cholesterol. Moreover, all the flavanone metabolites improved mitochondrial function and insulin secretion, and reduced apoptosis. Flavanone metabolites were found uptake by ß-cells, and therefore could be responsible for the observed protective effects. These results demonstrated that circulating phase-II hesperetin and naringenin metabolites, and also phenolics derived from gut microbiota, protect pancreatic-ß cells against oxidative stress, leading to an improvement in ß-cell function and could be the bioactive molecules derived from the citrus consumption.

Human urine metabolomic signature after ingestion of polyphenol-rich juice of purple grumixama (Eugenia brasiliensis Lam.).

Polyphenol intake has been associated with health promotion because of its interaction with several metabolic pathways. This study investigates changes in the urine metabolome following acute intake of polyphenol-rich juice, purple grumixama juice. Grumixama (Eugenia brasiliensis Lam.) is a cherry native to Brazil that is known to be a rich source of anthocyanins and ellagitannins. In this research 15 healthy subjects consumed a single dose of grumixama juice. Urine samples were collected before grumixama juice intake, 0-1, 1-2, 2-4 h, with fasting at 24 h after intake. Plasma samples were also collected before intake, 30' and at 1 h, 2 h and 4 h, with fasting at 24 h after juice intake. The urine primary metabolites were analysed by a metabolomic approach using gas chromatography mass spectrometry with methyl chloroformate derivatisation for amino acids and organic acids. Also, an oxygen radical absorbance capacity method was carried out to evaluate the plasma samples antioxidant capacity changes. Subjects showed increase in plasma antioxidant capacity after juice intake (p-values < .05). A total of 114 metabolites were assessed in urine (1-2 h and 2-4 h), including 17 amino acids, 47 organic acids and several other metabolites. Among the 114 metabolites, 25 were significantly changed during the first 4 h following juice intake, as shown by the Orthogonal Partial Least Squares Discriminant Analysis (0.5 > p(corr) > 0.3) and univariate analysis (p-values < .05). Some metabolites were related to mitochondrial metabolism, such as glyoxylic acid and oxalic acid. Metabolites related to amino acid metabolism were also changed, such as beta-alanine, l-phenylalanine and l-tyrosine. In conclusion, results suggest that acute intake of grumixama juice could affect amino acid metabolism and mitochondrial metabolism, but the related health implications should be explored in further studies using additional approaches.

Effect of Pasteurization on Flavonoids and Carotenoids in Citrus sinensis (L.) Osbeck cv. 'Cara Cara' and 'Bahia' Juices.

Orange juice is considered an excellent dietary source of several bioactive compounds with beneficial properties for human health. Citrus sinensis Osbeck cv. 'Cara Cara' is a bud mutation originated from 'Washington' navel orange, also known as 'Bahia' navel orange. The ascorbic acid, flavonoid, and carotenoid contents in pasteurized and nonpasteurized Bahia and Cara Cara juices using two LC-MS/MS platforms were investigated. Higher ascorbic acid content was observed in Bahia compared to Cara Cara in both pasteurized and nonpasteurized juices. Total flavanones content as well as hesperidin levels were higher in Cara Cara with respect to Bahia pasteurized juice. Cara Cara was also characterized by a significantly higher and diversified carotenoid content compared to Bahia juice with a mixture of (Z)-isomers of lycopene, all-E-ß-carotene, phytoene, and phytofluene isomers accounting for the highest carotenoid proportion. The exceptionally high carotenoid content of Cara Cara may be particularly interesting for nutritional or functional studies of uncommon carotenes in a citrus food matrix.

Phenolics and antioxidant properties of fruit pulp and cell wall fractions of postharvest banana (Musa acuminata Juss.) cultivars.

Banana fruits are important foods, but there have been very few studies evaluating the phenolics associated with their cell walls. In the present study, (+) catechin, gallocatechin, and (-) epicatechin, as well as condensed tannins, were detected in the soluble extract of the fruit pulp; neither soluble anthocyanidins nor anthocyanins were present. In the soluble cell wall fraction, two hydroxycinnamic acid derivatives were predominant, whereas in the insoluble cell wall fraction, the anthocyanidin delphinidin, which is reported in banana cell walls for the first time, was predominant. Cell wall fractions showed remarkable antioxidant capacity, especially after acid and enzymatic hydrolysis, which was correlated with the total phenolic content released after the hydrolysis of the water-insoluble polymer, but not for the posthydrolysis water-soluble polymer. The acid hydrolysis released various monosaccharides, whereas enzymatic hydrolysis released one peak of oligosaccharides. These results indicate that banana cell walls could be a suitable source of natural antioxidants and that they could be bioaccessible in the human gut.