Intestinal Microbiome Metabolism of Cranberry (Vaccinium macrocarpon) Proanthocyanidin Dimers, but Not Trimers, Is Altered by Dysbiosis in Ulcerative Colitis Ex Vivo.

Cranberries contain proanthocyanidins with different interflavan bond types and degrees of polymerization. These chemical differences may impact the metabolism of proanthocyanidins by the intestinal microbiome. In our previous study, we found that healthy microbiomes produced higher concentrations of the phenolic acid metabolites 5-(3',4'-dihydroxyphenyl)-g-valerolactone and 3-hydroxyphenylacetic acid from the cranberry extract in comparison to ulcerative colitis (UC) microbiomes ex vivo. To understand this difference, LC-ESI-MS/MS was utilized to characterize the metabolism of the precursor proanthocyanidins. Healthy microbiomes metabolized procyanidin A2, procyanidin B2, and procyanidin dimeric intermediates but not A-type trimers, to a greater extent than UC microbiomes. The metabolism of procyanidin A2 and procyanidin B2 by fecal microorganisms was then compared to identify their derived phenolic acid metabolites. 5-(3',4'-Dihydroxyphenyl)-g-valerolactone and 3-hydroxyphenylacetic acid were identified as unique metabolites of procyanidin B2. Based on these results, the metabolism of procyanidin B2 contributed to the differential metabolism observed between healthy and UC microbiomes.

Dark Sweet Cherry (Prunus avium) Supplementation Reduced Blood Pressure and Pro-Inflammatory Interferon Gamma (IFNγ) in Obese Adults without Affecting Lipid Profile, Glucose Levels and Liver Enzymes.

Dark sweet cherries (DSC) are rich in fiber and polyphenols that decrease risk factors associated with obesity. This single-blind randomized placebo-controlled study investigated DSC effects on inflammation, cardiometabolic, and liver health biomarkers in obese adults. Participants (>18 years, body mass index (BMI) = 30-40 kg/m2) consumed 200 mL of DSC drink (juice supplemented with DSC powder) (n = 19) or a placebo drink (n = 21) twice/day for 30 days. Anthropometric and physiological biomarkers were monitored at baseline (D1), mid-point (D15), and endpoint (D30) visits. Blood inflammatory biomarkers were assessed at D1, D15, and D30, and blood lipids, glucose, and liver enzymes at D1 and D30. DSC consumption lowered systolic blood pressure (SBP) (p = 0.05) and decreased diastolic blood pressure (DBP) compared to placebo (p = 0.04). Stratification of participants by BMI revealed a greater (p = 0.008) SBP reduction in BMI > 35 participants. DSC lowered pro-inflammatory interferon-gamma (IFNγ) (p = 0.001), which correlated with SBP changes. The interleukin (IL)-1RA and SBP changes were correlated in the placebo group, as well as triglycerides (TG) with DBP. The increased IL-10 levels in the placebo group suggested a compensatory mechanism to counteract elevated IFNγ levels. No significant between-group differences were detected for blood lipids, glucose, and liver enzymes. In conclusion, DSC helped to decrease blood pressure levels and inflammation in obese adults.

In vitro digestion, absorption and biological activities of acylated anthocyanins from purple sweet potatoes (Ipomoea batatas).

Purple sweet potatoes (PSP) are widely used as color enhancers in food formulations. Investigations on the stability of PSP polyphenolics during simulated digestion and subsequent absorption in a Caco-2 cell monolayer model were accomplished. Measures of bioactive activities were also assessed in vitro. PSP whole polyphenolic extracts as a control (WC) were compared to isolates enriched in anthocyanins (AC) or non-anthocyanin phenolics (NAP). Anthocyanins were also alkali-hydrolyzed to remove acylated moieties. Compounds were subjected to simulated gastro-intestinal digestions where non-hydrolyzed anthocyanins showed higher stability compared to alkali-hydrolyzed. For many alkali-hydrolyzed anthocyanins, the transport through a Caco-2 cell monolayer was reduced. PSP fractions significantly increased the generation of reactive oxygen species in HT-29 cells and was suppressive in the CCD-18Co cells while down-regulated mRNA expression of inflammatory markers. Results indicate the importance of PSP composition and the effects of acyl moieties on anthocyanin stability and functional properties for food colors.

Ulcerative colitis results in differential metabolism of cranberry polyphenols by the colon microbiome in vitro.

The microbiome plays a major role in polyphenol metabolism, producing metabolites that are bioavailable and potentially more bioactive than the compounds from which they are derived. However, the microbiome can vary among individuals, and especially for those with co-morbidities, such as ulcerative colitis. In subjects with ulcerative colitis, the consequence of a 'dysbiotic' microbiome is characterized by decreased diversity of microbiota that may impact their capability to metabolize polyphenols into bioavailable metabolites. On this premise, the microbiome metabolism of cranberry polyphenols between healthy individuals and those with ulcerative colitis was compared in vitro. Fecal samples from volunteers, with or without diagnosed ulcerative colitis, were cultured anaerobically in the presence of cranberry polyphenols. The resulting metabolites were then quantified via LC-ESI-MS/MS. 16S rRNA metagenomics analysis was also utilized to assess differences in microbiota composition between healthy and ulcerative colitis microbiomes and the modulatory effects of cranberry polyphenols on microbiota composition. Healthy microbiomes produced higher (p < 0.05) concentrations of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone and 3-hydroxyphenylacetic acid in comparison to ulcerative colitis microbiomes. Additionally, healthy microbiomes contained a higher (p < 0.05) abundance of Ruminococcaceae, which could explain their ability to produce higher concentrations of cranberry polyphenol metabolites. Health status and the presence of cranberry polyphenols also significantly impacted the production of several short-chain and branched-chain fatty acids. These results suggest that efficiency of polyphenol metabolism is dependent on microbiota composition and future works should include metabolite data to account for inter-individual differences in polyphenol metabolism.

Mango (Mangifera indica L.) Polyphenols: Anti-Inflammatory Intestinal Microbial Health Benefits, and Associated Mechanisms of Actions.

Mango is rich in polyphenols including gallotannins and gallic acid, among others. The bioavailability of mango polyphenols, especially polymeric gallotannins, is largely dependent on the intestinal microbiota, where the generation of absorbable metabolites depends on microbial enzymes. Mango polyphenols can favorably modulate bacteria associated with the production of bioactive gallotannin metabolites including Lactobacillus plantarum, resulting in intestinal health benefits. In several studies, the prebiotic effects of mango polyphenols and dietary fiber, their potential contribution to lower intestinal inflammation and promotion of intestinal integrity have been demonstrated. Additionally, polyphenols occurring in mango have some potential to interact with intestinal and less likely with hepatic enzymes or transporter systems. This review provides an overview of interactions of mango polyphenols with the intestinal microbiome, associated health benefits and underlying mechanisms.

Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation.

Dark sweet cherries (DSCs) are rich source of phenolics known to exert anticancer and anti-invasive activities. This study elucidated the molecular mechanisms underlying the activity of DSC phenolics against MDA-MB-453 breast cancer cells In Vitro. Cells were treated with DSC phenolics in whole extract (WE), and fractions enriched in anthocyanins (ACN) and proanthocyanidins (PCN) at concentrations that inhibited cell growth by 50%. Results showed that DSC phenolics suppressed Akt and PLCγ-1 activation, and inhibited cell motility and invasion, but only ACN reached significance. The extrinsic and intrinsic apoptotic pathways were also activated by DSC phenolics via caspase-8 cleavage and increased Bax/Bcl-2 ratio, with ACN exhibiting significant activation and stronger PARP-1 cleavage. Furthermore, sustained activation of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 was observed wherein ERK1/2 (U0126) and p38 (SB203580) inhibitors confirmed crosstalk ERK1/2-Akt and MAPK intrinsic mitochondrial pathways. In conclusion, DSC phenolics inhibited MDA-MB-453 breast cancer cells by targeting cell signaling pathways that induce apoptosis and suppress cell invasion, with ACN showing enhanced chemopreventive activities.

Mango (Mangifera indica L.) polyphenols reduce IL-8, GRO, and GM-SCF plasma levels and increase Lactobacillus species in a pilot study in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) characterized by chronic intestinal inflammation and intestinal microbial dysbiosis present a major risk factor in the development of colorectal cancer. Previously, dietary polyphenols from mango (Mangifera indica L.) such as gallotannins and gallic acid have been shown to mitigate intestinal inflammation and carcinogenesis, as well as modulate intestinal microbial composition. To further translate findings from preclinical models, we hypothesized that mango polyphenols possess anti-inflammatory and microbiome-modulatory activities and may improve symptoms of IBD, reduce biomarkers for inflammation and modulate the intestinal microbiome when administered as an adjuvant treatment in combination with conventional medications in patients with mild to moderate IBD. In this study, ten participants received a daily dose of 200-400 g of mango pulp for 8 weeks (NCT02227602). Mango intake significantly improved the primary outcome Simple Clinical Colitis Activity Index (SCCAI) score and decreased the plasma levels of pro-inflammatory cytokines including interleukin-8 (IL-8), growth-regulated oncogene (GRO) and granulocyte macrophage colony-stimulating factor (GM-CSF) by 16.2% (P = .0475), 25.0% (P = .0375) and 28.6% (P = .0485), all factors related to neutrophil-induced inflammation, respectively. Mango intake beneficially altered fecal microbial composition by significantly increasing the abundance of Lactobacillus spp., Lactobacillus plantarum, Lactobacillus reuteri and Lactobacillus lactis, which was accompanied by increased fecal butyric acid production. Therefore, enriching diet with mango fruits or potentially other gallotannin-rich foods seems to be a promising adjuvant therapy combined with conventional medications in the management of IBD via reducing biomarkers of inflammation and modulating the intestinal microbiota.

Improved recovery of galloyl metabolites from mango (Mangifera indica L.) in human plasma using protein precipitation with sodium dodecyl sulfate and methanol.

Extraction of polyphenolic metabolites from blood fractions can be challenging since compound recovery can be limited by chemical structure, polarity, and protein-binding affinity of analytes. Gallic acid and its metabolites exhibit particularly low recoveries from plasma and can lead to an underestimation of their bioavailability from foods. A modified method to extract free gallic acid and its metabolites from human plasma aided by sodium dodecyl sulfate and acidified methanol (SDS-MeOH) was applied to extract free gallic acid and its metabolites from human plasma after a single consumption of 400 g of mango (cv. Ataulfo) pulp by 10 healthy male and female subjects. The use of SDS-MeOH facilitated extraction of significantly (p < 0.05) more pyrogallol, free gallic acid, 4-O-methylgallic acid, and ethyl gallate with recovery rates exceeding 80% in standard recovery from human blood plasma when compared to conventional methods that rely on solvent extraction or solid phase extraction. The method was reproducible and precise for standards from 50 to 500 µg/L. In pharmacokinetic plasma samples five predominant metabolites of gallic acid were tentatively characterized by HPLC-MS and absorption kinetics evaluated over 8 h for catechol-O-sulfate, 4-O-methylgallic acid-3-O-sulfate, and pyrogallol-O-sulfate, methylpyrogallol-O-sulfate, and 4-O-methylgallic acid with AUC0-8h of 9520 ± 3370, 6030 ± 1310, 5990 ± 1690, 4020 ± 1040, and 2790 ± 1190 µg/L h respectively. Plasma extraction was rapid and reproducible with superior recovery rates compared to conventional methods when evaluating polar phenolic metabolites.

Chemical Genomic Profiling Unveils the in Vitro and in Vivo Antiplasmodial Mechanism of Açaí (Euterpe oleracea Mart.) Polyphenols.

Malaria remains a major detrimental parasitic disease in the developing world, with more than 200 million cases annually. Widespread drug-resistant parasite strains push for the development of novel antimalarial drugs. Plant-derived natural products are key sources of antimalarial molecules. Euterpe oleracea Martius ("açaí") originates from Brazil and has anti-inflammatory and antineoplasic properties. Here, we evaluated the antimalarial efficacy of three phenolic fractions of açaí; total phenolics (1), nonanthocyanin phenolics (2), and total anthocyanins (3). In vitro, fraction 2 moderately inhibited parasite growth in chloroquine-sensitive (HB3) and multiresistant (Dd2) Plasmodium falciparum strains, while none of the fractions was toxic to noncancer cells. Despite the limited activity in vitro, the oral treatment with 20 mg/kg of fraction 1 reduced parasitemia by 89.4% in Plasmodium chabaudi-infected mice and prolonged survival. Contrasting in vitro and in vivo activities of 1 suggest key antiplasmodial roles for polyphenol metabolites rather than the fraction itself. Finally, we performed haploinsufficiency chemical genomic profiling (HIP) utilizing heterozygous Saccharomyces cerevisiae deletion mutants to identify molecular mechanisms of açaí fractions. HIP results indicate proteostasis as the main cellular pathway affected by fraction 2. These results open avenues to develop açaí polyphenols as potential new antimalarial candidates.

Gallotannins and Lactobacillus plantarum WCFS1 Mitigate High-Fat Diet-Induced Inflammation and Induce Biomarkers for Thermogenesis in Adipose Tissue in Gnotobiotic Mice.

SCOPE: Intestinal microbial metabolites from gallotannins (GT), including gallic acid (GA) and pyrogallol (PG), may possess potential anti-obesogenic properties. Lactobacillus plantarum (L. plantarum) found in the intestinal microbiome encodes for enzymatic activities that metabolize GT into GA and PG. Anti-obesogenic activities of orally administered GT in the presence or absence of L. plantarum is examined in gnotobiotic mice fed a high-fat diet (HFD). METHODS AND RESULTS: Germ-free (GF) C57BL/6J mice are divided into three groups, GF control, GF gavaged with GT, and mice colonized with L. plantarum and gavaged with GT. Compared to the control, GT decreases the expressions of lipogenic genes (e.g., fatty acid synthase (FAS)) in epididymal white adipose tissue and increases thermogenic genes (e.g., nuclear factor erythroid-2-like 1 (Nfe2l1)) in interscapular brown adipose tissue. Intestinal colonization with L. plantarum enhances these effects, and mice colonized with L. plantarum exhibit lower levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), leptin and plasma insulin. CONCLUSIONS: Results indicate that GT and L. plantarum reduce HFD-induced inflammation, insulin resistance, and promote thermogenesis in adipose tissue potentially through the activity of GT-metabolizing bacterial enzymes yielding absorbable bioactive GT metabolites. These findings imply the potential role of prebiotic-probiotic interactions in the prevention of diet-induced metabolic disorders.

Body Mass Index as a Determinant of Systemic Exposure to Gallotannin Metabolites during 6-Week Consumption of Mango (Mangifera indica L.) and Modulation of Intestinal Microbiota in Lean and Obese Individuals.

SCOPE: This human clinical pilot trial investigated pharmacokinetics of gallotannin-metabolites and modulation of intestinal microbiota in healthy lean and obese individuals after 6 weeks of daily mango consumption. METHODS AND RESULTS: Participants are divided into three groups: Lean Mango (LM: n = 12; BMI = 22.9 kg m-2 ), Obese Mango (OM: n = 9; BMI = 34.6 kg m-2 ), and Lean Control (LC: n = 11; BMI = 22.1 kg m-2 ). LM and OM consumed 400 g of mango per day for 6 weeks. LC consumed mango only on Days 0 and 42. After 6 weeks, LM experienced increased systemic exposure (AUC0-8h ) to gallotannin-metabolites, 1.4-fold (p = 0.043). The greatest increase is 4-O-methyl-gallic acid, 3.3-fold (p = 0.0026). Cumulative urinary excretion of gallotannin-metabolites significantly increased in LM and OM, but not LC. For OM, qPCR data show increased levels of tannase-producing Lactococcus lactis and decreased levels of Clostridium leptum and Bacteroides thetaiotaomicron, bacteria associated with obesity. LM experienced an increased trend of fecal levels of butyric (1.3-fold; p = 0.09) and valeric acids (1.5-fold; p = 0.056). Plasma endotoxins showed a decreased trend in LM and OM. CONCLUSION: Continuous mango intake significantly increased systemic exposure to gallotannin- metabolites and induced an increased trend for fecal short-chain fatty acids in lean but not obese individuals. This pharmacokinetic discrepancy may result in BMI-associated reduced gallotannin-derived health benefits.

Non-anthocyanin phenolics in cherry (Prunus avium L.) modulate IL-6, liver lipids and expression of PPARδ and LXRs in obese diabetic (db/db) mice.

Anthocyanin-rich cherries are known for preventing/decreasing risk factors associated with obesity; however, the specific benefits exerted by cherry non-anthocyanin phenolics are not clear. Obese diabetic (db/db) mice fed a diet supplemented with anthocyanin-depleted cherry powder (cherry) were compared to db/db (obese) or lean counterparts (lean) fed a control isocaloric diet for 12 weeks. The reduced plasma interleukin (IL)-6 and improved liver health may be mediated by cherry fibre and non-anthocyanin phenolics. Benefits for liver health included reduction of lipids and protein carbonyls, and modulation of peroxisome proliferator-activated receptor (PPAR)δ mRNA to resemble levels in lean. Lack of plasma antilipidemic, improvement of antioxidant defenses, and PPARα/γ mRNA modulation in liver suggest cherry anthocyanins specific benefits. This is the first study to elucidate in vivo the potential benefits of cherry non-anthocyanin phenolics for diabetes-induced liver disorders and the importance of choosing processing technologies that preserve anthocyanins and health benefits of whole cherries.

Açaí (Euterpe oleracea Mart.) beverage consumption improves biomarkers for inflammation but not glucose- or lipid-metabolism in individuals with metabolic syndrome in a randomized, double-blinded, placebo-controlled clinical trial.

Açaí (Euterpe oleracea Mart.) berries, characterized by high polyphenol concentrations (predominantly anthocyanins), have demonstrated anti-inflammatory and anti-diabetic activities. The study objective was to determine the modulation of lipid and glucose-metabolism, as well as oxidative stress and inflammation, by an açaí-beverage (containing 1139 mg L-1 gallic acid equivalents of total polyphenolics) in 37 individuals with metabolic syndrome (BMI 33.5 ± 6.7 kg m-2) who were randomized to consume 325 mL twice per d of a placebo control or açaí-beverage for 12 weeks. Anthropometric measurements, dietary intake, and blood and urine samples were collected at baseline and after 12 weeks of consumption. Two functional biomarkers, plasma level of interferon gamma (IFN-γ) and urinary level of 8-isoprostane, were significantly decreased after 12 weeks of açaí consumption compared to the placebo control (p = 0.0141 and 0.0099, respectively). No significant modification of biomarkers for lipid- and glucose-metabolism was observed in this study. Findings from this small pilot study provide a weak indication that the selected dose of açaí polyphenols may be beneficial in metabolic syndrome as only two biomarkers for inflammation and oxidative stress were improved over 12 weeks. Follow-up studies should be conducted with higher polyphenol-doses before drawing conclusions regarding the efficacy of açaí polyphenols in metabolic syndrome.

Obesity-Associated Diseases Biomarkers Are Differently Modulated in Lean and Obese Individuals and Inversely Correlated to Plasma Polyphenolic Metabolites After 6 Weeks of Mango (Mangifera indica L.) Consumption.

SCOPE: Mangos are a rich source of gallotannin-derived polyphenols that may exert anti-inflammatory effects relevant to obesity-related chronic diseases. This randomized human clinical study investigated the influence of daily mango supplementation for 6 weeks on inflammation and metabolic functions in lean and obese individuals. METHODS AND RESULTS: Lean (n = 12, body mass index [BMI] 18-26.2 kg m-2 ) and obese (n = 9, BMI >28.9 kg m-2 ) participants, aged 18-65 years received daily 400 g of mango pulp for 6 weeks. Inflammatory cytokines, metabolic hormones, and lipid profiles were examined in plasma before and after 6 weeks. In lean participants, systolic blood pressure was lowered by 4 mmHg after 6 weeks. In obese participants, hemoglobin A1c (HbA1c) and plasminogen activator inhibitor-1 (PAI-1) were reduced by 18% and 20%, respectively. Obese participants showed decreased plasma concentrations (area under the curve [AUC] 0-8h ) of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1). Correlation analysis indicates that the beneficial effects of mango supplementation on pro-inflammatory cytokines, PAI-1 and HbA1c, are associated with systemic exposure to polyphenolic metabolites. CONCLUSIONS: Mango supplementation improves the plasma levels of pro-inflammatory cytokines and metabolic hormones in obese participants. There is a crucial need to investigate the role of lowered polyphenolic absorption in obese individuals on their efficacy in reducing biomarkers for inflammation and other risk factors for chronic diseases.

Polyphenol-rich Mango (Mangifera indica L.) Ameliorate Functional Constipation Symptoms in Humans beyond Equivalent Amount of Fiber.

SCOPE: Chronic constipation is a common gastrointestinal condition associated with intestinal inflammation and considerably impaired quality of life, affecting about 20% of Americans. Dietary fiber and laxatives aid in its treatment but do not fully address all symptoms, such as intestinal inflammation. Mango (Mangifera indica L.), a fiber- and polyphenol-rich fruit may provide anti-inflammatory effects in constipation. METHODS AND RESULTS: The 4 week consumption of mango fruit (300 g) or the equivalent amount of fiber is investigated in otherwise healthy human volunteers with chronic constipation who are randomly assigned to either group. Blood and fecal samples and digestive wellness questionnaires are collected at the beginning and end of the study. Results show that mango consumption significantly improve constipation status (stool frequency, consistency, and shape) and increase gastrin levels and fecal concentrations of short chain fatty acid (valeric acid) while lowering endotoxin and interleukin 6 concentrations in plasma. CONCLUSION: In this pilot study, the consumption of mango improves symptoms and associated biomarkers of constipation beyond an equivalent amount of fiber. Larger follow-up studies would need to investigate biomarkers for intestinal inflammation in more detail.

Effect of dark sweet cherry powder consumption on the gut microbiota, short-chain fatty acids, and biomarkers of gut health in obese db/db mice.

Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics) with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs) and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db) mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12) for 12 weeks; obese (n = 10) and lean (n = 10) mice served as controls and received a standard diet without cherry. High-throughput sequencing of the 16S rRNA gene and quantitative real-time PCR (qPCR) were used to analyze the gut microbiota; SCFAs and biomarkers of gut health were also measured using standard techniques. According to 16S sequencing, supplemented mice harbored a distinct colonic microbiota characterized by a higher abundance of mucin-degraders (i.e., Akkermansia) and fiber-degraders (the S24-7 family) as well as lower abundances of Lactobacillus and Enterobacteriaceae. Overall this particular cherry-associated colonic microbiota did not resemble the microbiota in obese or lean controls based on the analysis of weighted and unweighted UniFrac distance metrics. qPCR confirmed some of the results observed in sequencing, thus supporting the notion that cherry supplementation can change the colonic microbiota. Moreover, the SCFAs detected in supplemented mice (caproate, methyl butyrate, propionate, acetate and valerate) exceeded those concentrations detected in obese and lean controls except for butyrate. Despite the changes in microbial composition and SCFAs, most of the assessed biomarkers of inflammation, oxidative stress, and intestinal health in colon tissues and mucosal cells were similar in all obese mice with and without supplementation. This paper shows that dietary supplementation with cherry powder for 12 weeks affects the microbiota and the concentrations of SCFAs in the lower intestinal tract of obese db/db diabetic mice. These effects occurred in absence of differences in most biomarkers of inflammation and other parameters of gut health. Our study prompts more research into the potential clinical implications of cherry consumption as a dietary supplement in diabetic and obese human patients.

Effect of nanoencapsulation using PLGA on antioxidant and antimicrobial activities of guabiroba fruit phenolic extract.

Guabiroba fruit has been highlighted for its high phytochemical content, particularly of phenolic compounds. The stability, bioavailability, and bioactivity of these compounds can be enhanced by nanoencapsulation, to improve functionality. Poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles containing phenolic extract of guabiroba (GPE) were synthesized by an adapted emulsion-evaporation method and their physico-chemical and functional properties were studied at two lactic to glycolic acid ratios (50:50 and 65:35). Higher (P<0.05) or equivalent antioxidant capacity compared to free GPE were observed for GPE-loaded nanoparticles. Free extract and PLGA nanoparticles were effective inhibitors of Listeria innocua, with lower (P<0.05) GPE concentrations required for inhibition when nanoencapsulated. Also, reduction of ROS generation in non-cancer cells was achieved with lower GPE concentrations (P<0.05) after encapsulation. These results suggest that PLGA nanoparticles can be used as a delivery system for phenolic compounds at lower levels than originally required for enhanced functional properties.

Establishing Standards on Colors from Natural Sources.

Color additives are applied to many food, drug, and cosmetic products. With up to 85% of consumer buying decisions potentially influenced by color, appropriate application of color additives and their safety is critical. Color additives are defined by the U.S. Federal Food, Drug, and Cosmetic Act (FD&C Act) as any dye, pigment, or substance that can impart color to a food, drug, or cosmetic or to the human body. Under current U.S. Food and Drug Administration (FDA) regulations, colors fall into 2 categories as those subject to an FDA certification process and those that are exempt from certification often referred to as "natural" colors by consumers because they are sourced from plants, minerals, and animals. Certified colors have been used for decades in food and beverage products, but consumer interest in natural colors is leading market applications. However, the popularity of natural colors has also opened a door for both unintentional and intentional economic adulteration. Whereas FDA certifications for synthetic dyes and lakes involve strict quality control, natural colors are not evaluated by the FDA and often lack clear definitions and industry accepted quality and safety specifications. A significant risk of adulteration of natural colors exists, ranging from simple misbranding or misuse of the term "natural" on a product label to potentially serious cases of physical, chemical, and/or microbial contamination from raw material sources, improper processing methods, or intentional postproduction adulteration. Consistent industry-wide safety standards are needed to address the manufacturing, processing, application, and international trade of colors from natural sources to ensure quality and safety throughout the supply chain.

Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat.

SCOPE: The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model. METHODS AND RESULTS: (ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8-h pharmacokinetic study was performed. After 24 h, a second dose of SGP was administered and 1 h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished Cmax for all catechin, epicatechin, quercetin and resveratrol conjugated metabolites. Bioavailability was significantly lower in ZDF rats for methylated flavan-3-ol, RES, and quercetin metabolites. Significantly lower levels of metabolites of RES, quercetin, and flavan-3-ols were found in brains of ZDF rats. There was no significant difference between ZDF and LN in anthocyanins in plasma and no anthocyanins were detectable in brain extracts. ZDF rats showed significantly higher urinary excretion for all polyphenols. CONCLUSION: Diabetes may alter the overall bioavailability of some polyphenols in plasma and brain in part due to higher urinary clearance.

Pomegranate polyphenolics reduce inflammation and ulceration in intestinal colitis-involvement of the miR-145/p70S6K1/HIF1α axis in vivo and in vitro.

This study investigated the potential role of the p70S6K1/HIF1α axis in the anti-inflammatory activities of pomegranate (Punica granatum L.) polyphenolics in dextran sodium sulfate (DSS)-induced colitis in Sprague-Dawley rats and in lipopolysaccharide (LPS)-treated CCD-18Co colon-myofibroblastic cells. Rats were administered either control (CT) or pomegranate beverage (PG), containing ellagic acid and ellagitannins, then exposed to three cycles of 3% DSS followed by a 2-week recovery period. PG protected against DSS-induced colon inflammation and ulceration (50% and 66.7%, P=.05 and .045, respectively), and decreased the Ki-67 proliferative index in the central and basal regions compared to the control. PG also significantly reduced the expression of proinflammatory cytokines (TNF-α and IL-1ß), COX-2, and iNOS at mRNA and protein levels. In addition, the expression of p70S6K1 and HIF1α was reduced, while the tumor suppressor miR-145 was induced by PG. The intestinal microbiota of rats treated with PG showed a significant increase in Ruminococcaceae that include several butyrate producing bacteria (P=.03). In vitro, PG reduced the expression of p70S6K1 and HIF1α and induced miR-145 in a dose-dependent manner. The involvement of miR-145/p70S6K1 was confirmed by treating LPS-treated CCD-18Co cells with miR-145 antagomiR, where the pomegranate polyphenolics reversed the effects of the antagomiR for p70S6K1 mRNA and protein levels. These results suggest that pomegranate polyphenols attenuated DSS-induced colitis by modulating the miR-145/p70S6K/HIF1α axis, indicating potential use in therapeutic treatment of ulcerative colitis.