Long-term supplementation with phenolic compounds from jaboticaba (Plinia jaboticaba (Vell.) Berg) reduces adiposophaty and improves glucose, lipid, and energy metabolism.

Obesity is a critical public health problem worldwide that has been associated to non-communicable diseases (NCD), such as type 2 diabetes (T2DM), non-alcoholic fatty lipid diseases (NAFLD) and inflammatory diseases. Polyphenols from several food sources have been studied as one option against these health problems. Sabara jaboticaba (Plinia jaboticaba (Vell.) Berg) is a Brazilian berry rich in ellagic acid derivatives and anthocyanins. Here we investigated the effects of a phenolic-rich extract from Sabara jaboticaba (PEJ) in a diet-induced obesity animal model. PEJ at two doses, 50 mg gallic acid equivalent (GAE)/kg body weight (BW) and 100 mg GAE/kg BW, were administered by daily gavage to obese C57BL/6J mice for 14 weeks. PEJ prevented the excessive body weight and adiposity, adipocyte hypertrophy, inflammation, hyperglycemia, glucose intolerance, insulin resistance, hypercholesterolemia, and hepatic lipid accumulation, as well as increased energy expenditure. In conclusion, polyphenols from Sabara jaboticaba presented several powerful therapeutic properties relevant for fighting obesity and associated health problems.

Postprandial glucose-lowering effect of cagaita (Eugenia dysenterica DC) fruit juice in dysglycemic subjects with metabolic syndrome: An exploratory study.

Cagaita (Eugenia dysenterica DC) is an ellagitannin-containing Myrtaceae fruit from Cerrado biome. This fruit seems to be a promising candidate for an adjuvant in glucose regulation in healthy subjects. However, it is not known whether cagaita juice would have the same effect on dysglycemic subjects with metabolic syndrome (MetS). Therefore, the present work aimed to evaluate the effect of cagaita fruit juice on postprandial glycemia in dysglycemic subjects with MetS, and whether cagaita ellagitannins could be metabolized to urolithins. To evaluate glycemic effects, two different meals were consumed by volunteers (n = 12) with a 1-week interval among them. The first one consisted of white bread (50 g) plus water (300 mL) as a control; the second one, white bread (50 g) plus clarified cagaita juice (300 mL). Bioavailability was assessed in 24 h urine, after the consumption of a single amount of 300 mL of cagaita juice by healthy (n = 16) and MetS subjects (n = 7). The results showed that dysglycemic subjects with MetS presented a 53% reduction of incremental area under the curve (iAUC) of glucose, 38% reduction of insulin, 78% reduction of GIP (glucose-dependent insulinotropic polypeptide), and 58% reduction of C-peptide (p < 0.05), after the consumption of cagaita juice along with bread, in comparison to control water. However, both GLP-1 (glucagon-like peptide-1) and glucagon were not affected by cagaita juice ingestion. Concerning bioavailability, it was observed, for the first time, the metabolization of cagaita ellagitannins to urolithins by healthy and dysglycemic individuals with MetS, with a prevalence of metabotype B in both groups (44% and 42%, respectively), followed by metabotype A (37% and 29%, respectively), and metabotype 0 (19% and 29%, respectively).

Phenolic compounds from jaboticaba (Plinia jaboticaba (Vell.) Berg) ameliorate intestinal inflammation and associated endotoxemia in obesity.

Jaboticaba (Plinia jaboticaba (Vell.) Berg) is a Brazilian native fruit belonging to the Myrtaceae family. Previously it was demonstrated that phenolic-rich extracts from jaboticaba (PEJ) possess health-beneficial properties in diet-induced obesity; however, whether PEJ modulates the obesity-associated intestinal inflammatory status remains unclear. Thus, male C57BL/6J obese mice were fed a high-fat-sugar (HFS) diet and received PEJ at two doses, 50 mg gallic acid equivalent (GAE)/kg body weight (BW) (PEJ1 group), and 100 mg GAE/kg BW (PEJ2 group), or water (HFS group) by oral gavage for 14 weeks. PEJ groups presented a reduced body weight gain and adiposity and were protected against insulin resistance and dyslipidemia. In addition, PEJ prevented metabolic endotoxemia linked to an attenuation of the HFS diet-induced intestinal inflammation via down-regulation of pro-inflammatory mediators such as tumor necrosis factor (TNF-α), membrane transporter toll-like receptor-4 (TLR-4) and nuclear factor-κB (NF-κB) in the colon. These anti-inflammatory effects appear to be involved, at least in part, with an inhibition of the colonic inflammasome pathway of obese mice.

Polyphenols of cambuci (Campomanesia phaea (O. Berg.)) fruit ameliorate insulin resistance and hepatic steatosis in obese mice.

Polyphenols from cambuci (CBC) (Campomanesia phaea (O. Berg.)), a Brazilian native fruit, were investigated on therapeutic actions mitigating insulin resistance and hepatic steatosis in high-fat-sucrose diet (HFS) induced obese mice. For this, C57BL/6J mice fed with a obesogenic and diabetogenic HFS diet were administered with either water or two CBC doses (36 or 74 mg gallic acid equivalent (GAE)/kg body weight) by gavage from week 6 to week 14 (end-point) of HFS feeding. CBC reduced body weight gain, inflammation, hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance in liver and skeletal muscle of obese mice, and such effects were associated with activation of Akt and AMPK in these tissues. In conclusion, polyphenols from CBC show important therapeutic actions ameliorating obesity-associated complications.

Response surface optimization of phenolic compounds from jabuticaba (Myrciaria cauliflora [Mart.] O.Berg) seeds: Antioxidant, antimicrobial, antihyperglycemic, antihypertensive and cytotoxic assessments.

The aim of this study was to evaluate the effects of different solvents and maximize the extraction of bioactive compounds from jabuticaba (Myrciaria cauliflora) seeds. In general, the solvent system composed of water and propanone (52:48 v/v) modified the extract polarity and increased extraction yield of bioactive compounds. The optimized extract presented antioxidant capacity measured by different chemical and biological assays. The optimized extract exerted antiproliferative and cytotoxic effects against A549 and HCT8 cells, antimicrobial and antihemolytic effects, inhibited α-amylase/α-glucosidase activities and presented in vitro antihypertensive effect. Nonetheless, the optimized extract showed no cytotoxicity in a human cell model (IMR90). Vescalagin, castalagin and ellagic acid were the major phenolic compounds in the optimized extract. Our results show that jabuticaba seed may be a potential ingredient for the development of potentially functional foods.

Clitoria ternatea L. petal bioactive compounds display antioxidant, antihemolytic and antihypertensive effects, inhibit α-amylase and α-glucosidase activities and reduce human LDL cholesterol and DNA induced oxidation.

The purpose of this study was to use a statistical approach to optimise the experimental conditions regarding the extraction of bioactive compounds, and to analyse the in vitro functional properties of crude lyophilized extracts (CLE) and partially purified (PPE) extracts of Clitoria ternatea petals. The results showed that the factors of temperature and time influenced the extraction of phenolic compounds, antioxidant activity and the physicochemical parameters. Simultaneous optimisation showed that the same levels of bioactive compounds were extracted when using temperatures from 11.7 to 68.3 °C and times from 8.47 to 51.12 min. Principal component analysis revealed the experimental conditions that provided the extraction producing the highest level of phenolic content (40 °C/30 min). The CLE showed antimicrobial activity; protective effect against hemolysis of erythrocytes; inhibition of α-amylase, α-glucosidase and angiotensin-I-converting (ACE-I) enzymes; and inhibition of lipid peroxidation. The CLE and PPE demonstrated oxygen radical absorption capacity; inhibition of DNA strand scission; inhibition of LDL cholesterol oxidation; intracellular antioxidant activity against reactive oxygen species (>100 µg/mL); and no cytotoxicity (IC50, GI50 and LC50 > 900 µg/mL) against A549, HCT8 and IMR90 cell lines.

Impact of combining acerola by-product with a probiotic strain on a gut microbiome model.

In this study, we first investigated the survival of three probiotic strains, individually and combined with acerola by-product during simulated gastrointestinal conditions. Next, we investigated the effects of acerola by-product combined with Bifidobacterium longum BB-46 on a gut microbiota model (SHIME®). Chemical composition, total phenolic compounds, antioxidant activity of the acerola by-product and microbial counts, denaturing gradient gel electrophoresis (DGGE), ammonium ions ( NH4+ ) and short-chain fatty acids (SCFAs) analysis of the SHIME® samples were performed. Acerola by-product revealed high protein and fibre, reduced lipid contents, and showed to be an excellent source of total phenolic compounds with high in vitro antioxidant activity. A decreased amount of NH4+ in the ascending colon and an increase (p < .05) in SCFAs were observed in the three regions of colon during treatment with BB-46 and acerola by-product. BB-46 combined with acerola by-product showed positive effects on the gut microbiota metabolism in SHIME® model.

Cagaita fruit (Eugenia dysenterica DC.) and obesity: Role of polyphenols on already established obesity.

Polyphenol-rich cagaita (Eugenia dysenterica DC.) extracts (PCE) have previously shown to prevent body weight and adiposity induced by high-fat/high-sucrose (HFS) diet. Whether PCE also exerts protective effects in already developed obesity is unknown. In order to test this hypothesis, male C57BL/6J obese mice (previously feed with a HFS diet for six weeks) were treated with PCE at two doses, 7mg gallic acid equivalent (GAE)/kg body weight (PCE I group), and 14mg GAE/kg body weight (PCE II group) or water (HFS and Chow groups) by oral gavage for eight weeks. PCE did not affect body weight and adiposity of obese mice. However, PCE did protect against dyslipidemia, fasting hyperglycemia, and glucose intolerance, and attenuated both hepatic gluconeogenesis and inflammation as observed by the expression of tumor necrosis factor-α and transcriptional factor NF-κB. These results indicate that PCE improves glucose homeostasis of obese mice by attenuating hepatic gluconeogenesis and inflammation.

Effect of clarified Brazilian native fruit juices on postprandial glycemia in healthy subjects.

Brazilian native fruits have been shown as excellent sources of polyphenols which are associated with multiple biological activities including inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase. Postmeal blood glucose elevations and high glycemic index diets can play a major role in the development of type 2 diabetes, therefore alternative approaches to reduce postprandial hyperglycemia are of growing interest in order to reduce diabetes risk. Here we investigated the effect of six Brazilian native clarified fruit juices from Amazon, Savannah and Atlantic Forest biomes on postprandial glycemia after consumption of a carbohydrate meal. For this, 23 healthy subjects were selected to consume seven meal tests, with a 1-week interval among them, consisting in 50g white bread plus 300mL of water (control) or cambuci, cagaita, maracujá-alho, cupuaçu, camu-camu and jaboticaba clarified fruit juices. The results showed that serum glucose concentrations were significantly lower after consumption of cambuci, cagaita, camu-camu and jaboticaba juices, whereas maracujá-alho and cupuaçu juices did not decrease the amount of glucose absorbed, compared to control (p<0.05). In addition, cagaita, cambuci, cupuaçu and jaboticaba juices increased the oxygen radical absorbance capacity in plasma, whereas all juices augmented the ferric reducing ability of plasma, except for cambuci (p<0.05). These results indicate that juices from Brazilian native fruits may be considered as adjuvant treatment for reduction of postprandial glycemia in healthy subjects.

Effects of Spray-Drying Parameters on In Vitro Functional Properties of Camu-Camu (Myrciaria dubia Mc. Vaugh): A Typical Amazonian Fruit.

Camu-camu (Myrciaria dubia) fruit is a rich source of bioactive compounds but its shelf life is rather short. Therefore, this study was aimed to evaluate the effect of inlet air temperature (T) and concentration (C) of maltodextrin and arabic gum on the spray-drying process of commercial camu-camu pulps (São Paulo and Manaus). Moisture, solubility, total phenolics (TP), ascorbic acid (AA), and proanthocyanidins (PAC) contents, and in vitro antioxidant capacity of the powders (FRAP, DPPH, Folin-Ciocalteu's reducing capacity were measured). Arabic gum resulted in better yields (22% to 30%), powder solubility (84% to 90%), and lower losses of analyzed compounds than the powders manufactured with maltodextrin. Overall, inlet air temperature had a lower impact on the responses studied than the concentration of carrier agents. Polynomial equations were generated for AA (R2 = 0.993), TP (R2 = 0.735), PAC (R2 = 0.946), and for the antioxidant capacity assays (0.867 ≤ R2  ≤ 0.963). In addition, principal component analysis showed that the lowest concentration of carrier agents (6%) in spray drying resulted in the lowest losses of bioactive compounds and, consequently, the highest antioxidant capacity.

Physicochemical variability of cambuci fruit (Campomanesia phaea) from the same orchard, from different locations and at different ripening stages.

BACKGROUND: The present study evaluated the variability of cambuci fruit (Campomanesia phaea) cultivated in São Paulo State in the towns of Mogi das Cruzes, Paraibuna, Paranapiacaba and Rio Grande da Serra, and characterized it at different maturity stages with respect to size, firmness, soluble solids content, titratable acidity, phenolic content, ethylene production, respiration rate and in vitro antioxidant capacity. RESULTS: Ripe fruit from the same locality, Paraibuna, showed large variations in size and acidity. Ripe fruit from different towns showed significant variation of total phenolics and, consequently, variation in antioxidant capacity. During maturation, the phenolic content and firmness decreased from unripe to ripe stages. The total soluble solids/titratable acidity ratio can be used as a parameter to differentiate cambuci at different maturity stages. However, the decrease in firmness combined with the absence of an ethylene climacteric peak does not allow us to conclude whether cambuci is climacteric or non-climacteric. CONCLUSION: Genetic and soil composition studies are needed to assess the reasons for the differences found among fruit from the same location, as well as the variability among fruit harvested in four localities. The best parameters for assessing the maturity stages of cambuci comprise the rounding of its corners and its firmness because the more mature the pulp, the softer is the fruit. © 2016 Society of Chemical Industry.

Antioxidant effects of proanthocyanidin-rich natural extracts from grape seed and cupuassu on gastrointestinal mucosa.

BACKGROUND: The gastrointestinal tract (GI) is constantly exposed to reactive species released by the GI tract itself, and those present in food and beverages. Phenolic compounds may help in protecting the GI tract against damage produced by the reactive species. In this paper we have analyzed the effects of a grape seed proanthocyanidin extract (GSPE) on reactive oxygen species (ROS) production in two different intestinal cell types: the absorptive cell line Caco-2 and the enteroendocrine cell line STC-1. RESULTS: We show that GSPE prevents tert-butylhydroperoxide-induced oxidative stress in both cell lines, and that the effects are dose and time dependent. We have also analyzed whether GSPE has any in vivo effect, and found that 25 mg kg(-1) body weight cannot counteract the increase in intestinal ROS induced by the cafeteria diet. However, an acute (1 h) treatment of 1 g GSPE kg(-1) body weight reduced ROS in fasted animals and also decreased ROS induction by food. These effects were found only after a short-term treatment. Furthermore, we have compared the in vitro GSPE effects with those of another proanthocyanidin-rich extract from cupuassu seeds, though it has compounds with different structures. Cupuassu extract also shows antioxidant effects in both cell types, which suggests different mechanisms from those of GSPE. CONCLUSION: Natural proanthocyanidin-rich extracts have an antioxidant effect in the GI tract, acting on absorptive cells and enterohormone-secreting cells, although the effects depend on the dose and period of treatment. © 2015 Society of Chemical Industry.

Effects of time and extraction temperature on phenolic composition and functional properties of red rooibos (Aspalathus linearis).

This work was aimed at assessing the time-temperature effects on the phenolic compounds and in vitro functional properties of aqueous extracts from red rooibos (Aspalathus linearis). The major phenolic composition (tannins, flavonoids, flavonols, ortho-diphenols, total phenolic content), antioxidant (ABTS and DPPH) and reducing capacities (FRAP and total reducing capacity), antimicrobial effects and inhibition of α-amylase/α-glucosidase were measured. Phenolic compounds were also determined by LC-ESI-MS/MS. Aqueous extracts did not inhibit the growth of Escherichia coli, Staphylococcus aureus, and Candida albicans between 7.81 and 1000mgL-1. Rooibos extracted at 85°C for 10min showed a beneficial interaction with the human erythrocytes, reducing the hemolysis. The correlation analysis showed that the phenolic compounds responsible for the inhibition of α-amylase (IC50) were isohrmanetin, isoquercitrin, luteolin, salicylic acid, and syringaldehyde, whereas the inhibition of α-glucosidase was correlated to syringaldehyde, isoquercitrin, and luteolin. Overall, rooibos extracted at 85°C had the highest antioxidant activity measured by all assays, higher contents of phenolic compounds (spectrophotometric and LC-ESI-MS/MS data), and lower IC50 values for the digestive enzymes. On the other hand, rooibos extracted at 65°C had the opposite behavior, while rooibos extracted at 75°C presented mean intermediate values for the responses. This result clearly indicates that the extraction temperature is the main factor leading to a higher extraction of bioactive compounds from red rooibos.

Aqueous extract of Rosmarinus officinalis L. inhibits neutrophil influx and cytokine secretion.

Rosmarinus officinalis L. phenolic compounds have attracted considerable attention because of their antioxidant and antimicrobial properties, including its ability to treat inflammatory disorders. In this work, we investigated the in vivo and in vitro effects of R. officinalis aqueous extract on neutrophil trafficking from the blood into an inflamed tissue, on cell-derived secretion of chemical mediators, and on oxidative stress. Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Wistar rats orally treated with the R. officinalis extract (100, 200, or 400 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (prostaglandin E2 (PGE2), TNF-α, interleukin 6 (IL-6), leukotriene B4 (LTB4), and cytokine-induced neutrophil chemoattractant 1 by enzyme-linked immunosorbent assay), and the anti-oxidative profile (super oxide dismutase (SOD), glutathione peroxidase, and thiobarbituric acid reactive substance (TBARS) spectrophotometry) were quantified in the inflamed exudate. N-Formyl-methionine-leucine-phenylalanine-induced chemotaxis, lipopolysaccharide-induced NO2 (-) production (Greiss reaction), and adhesion molecule expression (flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 µg/mL). Animals orally treated with phosphate-buffered saline and neutrophils incubated with Hank's balanced salt solution were used as control. R. officinalis extract oral treatment caused a dose-dependent reduction in the neutrophil migration as well as decreased SOD, TBARS, LTB4, PGE2, IL-6, and TNF-α levels in the inflamed exudate. In vitro treatment with R. officinalis decreased neutrophil chemotaxis, NO2 (-) production, and shedding of L-selectin and ß2 integrin expressions. Results here presented show that R. officinalis aqueous extract displays important in vivo and in vitro anti-inflammatory actions by blocking pathways of neutrophil migration and secretion, suggesting its therapeutic application to acute inflammatory reactions.

Functional properties and stability of spray-dried pigments from Bordo grape (Vitis labrusca) winemaking pomace.

The stability of anthocyanin and phenolic compounds, the antioxidant capacity, the antimicrobial activity and the capacity to inhibit arginase from Leishmania were evaluated in spray-dried powders from Bordo grape winemaking pomace extract. The pigments were produced using maltodextrin as the carrier agent at concentrations varying from 10% to 30% and air entrance temperatures varying from 130 to 170°C. A sample of freeze-dried extract without the carrier was also evaluated. The anthocyanins in the spray-dried samples showed good stability during storage, better than the freeze-dried and liquid extracts. The samples were capable of inhibiting the growth of Staphylococcus aureus and Listeria monocytogenes and showed high inhibitory capacity against the enzyme arginase from Leishmania. These results provide evidence that Bordo grapes from the winemaking process have the potential to be used as natural pigments with functional properties.

Frozen pulp extracts of camu-camu (Myrciaria dubia McVaugh) attenuate the hyperlipidemia and lipid peroxidation of Type 1 diabetic rats.

Several epidemiological and experimental studies demonstrate that modulation of inflammatory response and oxidative stress by natural phytochemicals is a promising strategy to prevent and treat many chronic inflammatory diseases. Camu-camu is an Amazonian fruit with a high content of antioxidants, especially phenolic compounds and vitamin C. In the present study we evaluated the in vivo effects of chronic ingestion of raw extracts derived from camu-camu (Myrciaria dubia McVaugh) frozen pulp on plasma lipid profile and oxidative stress in streptozotocin-induced diabetic rats. Oral administration of camu-camu raw extracts significantly increased plasma antioxidant activity, reduced triacylglycerol and total cholesterol and lipid peroxidation in the plasma of streptozotocin-induced diabetic rats. However, no effect was observed on glucose metabolism of diabetic rats, probably due to the severity of this model.

Theophylline is able to partially revert cachexia in tumour-bearing rats.

BACKGROUND AND AIMS: The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves) on a rat model of cancer cachexia. METHODS: The in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. RESULTS: Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart), which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. CONCLUSION: Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.

Potential dietary sources of ellagic acid and other antioxidants among fruits consumed in Brazil: jabuticaba (Myrciaria jaboticaba (Vell.) Berg).

BACKGROUND: The objectives of this study were (1) to evaluate the content of ellagic acid in fruits consumed by the Brazilian population, including native ones; (2) to further characterize rich sources in relation to ascorbic acid, phenolics contents and in vitro antioxidant capacity; and (3) to study the distribution and effect of ripening stage on ellagitannins content of jabuticaba (Myrciaria jaboticaba). The content of free ellagic acid and ellagic acid derivatives such as ellagitannins was analyzed using high-performance liquid chromatography (HPLC). RESULTS: Ellagic acid was detected in 10 out of a total of 35 fruits analyzed. The content of free ellagic acid in fruits varied from 0.0028 to 0.085 g kg(-1) (FW) and total ellagic acid varied from 0.215 to 3.11 g kg(-1) (FW). All the seven fruits belonging to the Myrtaceae family evaluated in this study presented high contents of ellagitannins in their composition, with jabuticaba, grumixama and cambuci (all native from Brazil) showing the highest total ellagic acid contents. Jabuticaba, the most consumed in Brazil among those and already adapted to commercial plantations, contained concentrated phenolics compounds, including ellagitannins, in the peel. Anthocyanins (cyanidin derivatives) increased significantly through ripening of jabuticaba and were not present in the pulp or seeds. Samples collected from three different locations during summer, winter and spring had total ellagic contents varying from 1.88 to 3.31 g kg(-1) (FW). The decrease in ellagic acid content with ripening was more accentuated for pulp (eight times) compared to seeds (2.3 times) and peel (2.0 times). CONCLUSION: These results showed the potential of jabuticaba as dietary source of ellagic acid and reinforced consumption of the whole fruit by the population.

Antioxidant capacity and mineral content of pulp and peel from commercial cultivars of citrus from Brazil.

Four Citrus species (C. sinensis, cvs. Pera and Lima; C. latifolia Tanaka cv. Tahiti; C. limettioides Tanaka cv. Sweet lime and C. reticulate, cv. Ponkan) grown in Brazil were characterised in relation to contents of minerals, ascorbic acid, total polyphenols and antioxidant capacity of pulps and peels. In general, the peels demonstrated significantly higher contents of all compounds than the pulps (p<0.05), with the exception of the Pera orange pulp that presented the highest acid ascorbic content (68 mg/100 ml), while the Tahiti lime peel presented the lowest (8 mg/100 g). Citrus showed high levels of potassium, calcium and magnesium, and the peels were considered sources of these minerals. The Ponkan mandarin peel presented the highest antioxidant capacity. The antioxidant capacity of citrus was correlated both to vitamin C and phenolics. Aside from citrus pulps, the peels are also good sources of bioactive compounds and minerals, and can be explored for their health promoting values in food products.