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.

Dark Sweet Cherry (Prunus avium) Anthocyanins Suppressed ERK1/2-Akt/mTOR Cell Signaling and Oxidative Stress: Implications for TNBC Growth and Invasion.

This study aimed to assess dark sweet cherry (DSC) total polyphenols (WE) and anthocyanins (ACN) against metastatic breast cancer (BC). The WE and ACN anticancer activity and underlying mechanisms were assessed in vitro using 4T1 BC cells. A pilot study using a BALB/C mouse syngeneic model bearing 4T1 tumors assessed the anti-metastatic potential of ACN in vivo. ACN inhibited cell viability with higher potency than WE and reduced reactive oxygen species (ROS) (IC50 = 58.6 µg cyanidin 3-glucoside equivalent (C3G)/mL or 122 µM). ACN induced p38 stress-related intrinsic apoptosis, leading to caspase-3 cleavage and total PARP decrease. ACN suppressed ERK1/2 and Akt/mTOR signaling pathways, which are abnormally activated in BC and promote motility and invasion. This was consistent with suppression of VCAM-1 mRNA, Scr phosphorylation and 88.6% reduction of cells migrating to wounded area. The pilot in vivo results supported the ACN-mediated suppression of angiogenesis in tumors and lungs. ACN also lowered Cenpf mRNA in lungs, associated with lung metastasis lesions and poor survival. Results demonstrated the dual Akt-ERK inhibitory role of ACN and suppression of their downstream pro-invasive targets. These results encourage a larger scale in vivo study to confirm that ACN may help to fight BC invasion and metastasis.

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.

Nutritional Aspects of Ecologically Relevant Phytochemicals in Ruminant Production.

This review provides an update of ecologically relevant phytochemicals for ruminant production, focusing on their contribution to advancing nutrition. Phytochemicals embody a broad spectrum of chemical components that influence resource competence and biological advantage in determining plant species' distribution and density in different ecosystems. These natural compounds also often act as plant defensive chemicals against predatorial microbes, insects, and herbivores. They may modulate or exacerbate microbial transactions in the gastrointestinal tract and physiological responses in ruminant microbiomes. To harness their production-enhancing characteristics, phytochemicals have been actively researched as feed additives to manipulate ruminal fermentation and establish other phytochemoprophylactic (prevent animal diseases) and phytochemotherapeutic (treat animal diseases) roles. However, phytochemical-host interactions, the exact mechanism of action, and their effects require more profound elucidation to provide definitive recommendations for ruminant production. The majority of phytochemicals of nutritional and pharmacological interest are typically classified as flavonoids (9%), terpenoids (55%), and alkaloids (36%). Within flavonoids, polyphenolics (e.g., hydrolyzable and condensed tannins) have many benefits to ruminants, including reducing methane (CH4) emission, gastrointestinal nematode parasitism, and ruminal proteolysis. Within terpenoids, saponins and essential oils also mitigate CH4 emission, but triterpenoid saponins have rich biochemical structures with many clinical benefits in humans. The anti-methanogenic property in ruminants is variable because of the simultaneous targeting of several physiological pathways. This may explain saponin-containing forages' relative safety for long-term use and describe associated molecular interactions on all ruminant metabolism phases. Alkaloids are N-containing compounds with vast pharmacological properties currently used to treat humans, but their phytochemical usage as feed additives in ruminants has yet to be exploited as they may act as ghost compounds alongside other phytochemicals of known importance. We discussed strategic recommendations for phytochemicals to support sustainable ruminant production, such as replacements for antibiotics and anthelmintics. Topics that merit further examination are discussed and include the role of fresh forages vis-à-vis processed feeds in confined ruminant operations. Applications and benefits of phytochemicals to humankind are yet to be fully understood or utilized. Scientific explorations have provided promising results, pending thorough vetting before primetime use, such that academic and commercial interests in the technology are fully adopted.

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.

Antitumor potential of dark sweet cherry sweet (Prunus avium) phenolics in suppressing xenograft tumor growth of MDA-MB-453 breast cancer cells.

This study investigated in vivo the antitumor activity of dark sweet cherry (DSC) whole extracted phenolics (WE) and fractions enriched in anthocyanins (ACN) or proanthocyanidins (PCA) in athymic mice xenografted with MDA-MB-453 breast cancer cells. Mice were gavaged with WE, ACN or PCA extracts (150 mg/kg body weight/day) for 36 days. Results showed that tumor growth was suppressed at similar levels by WE, ACN and PCA compared to control group (C) without signs of toxicity or significant changes in mRNA oncogenic biomarkers in tumors or mRNA invasive biomarker in distant organs. Tumor protein analyses showed that WE, ACN and PCA induced at similar levels the stress-regulated ERK1/2 phosphorylation, known to be linked to apoptosis induction. However, ACN showed enhanced antitumor activity through down-regulation of total oncogenic and stress-related Akt, STAT3, p38, JNK and NF-kB proteins. In addition, immunohistochemistry analysis of Ki-67 revealed inhibition of tumor cell proliferation with potency WE ≥ ACN ≥ PCA. Differential quantitative proteomic high-resolution nano-HPLC tandem mass spectrometry analysis of tumors from ACN and C groups revealed the identity of 66 proteins associated with poor breast cancer prognosis that were expressed only in C group (61 proteins) or differentially up-regulated (P<.05) in C group (5 proteins). These findings revealed ACN-targeted proteins associated to tumor growth and invasion and the potential of DSC ACN for breast cancer treatment. Results lead to a follow-up study with highly immunodeficient mice/invasive cell line subtype and advanced tumor development to validate the anti-invasive activity of DSC anthocyanins.

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.

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.

Ghrelin Signaling in Immunometabolism and Inflamm-Aging.

Intracellular changes in immune cells lead to metabolic dysfunction, which is termed immunometabolism. Chronic inflammation is a hallmark of aging; this phenomenon is described as inflamm-aging. Immunometabolism and inflamm-aging are closely linked to obesity, insulin resistance, type 2 diabetes (T2D), cardiovascular diseases, and cancers, which consequently reduce life span and health span of the elderly. Ghrelin is an orexigenic hormone that regulates appetite and food intake. Ghrelin's functions are mediated through its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin and GHS-R have important roles in age-associated obesity, insulin resistance, and T2D. In this chapter, we have discussed the roles of ghrelin signaling in diet-induced obesity and normal aging as it relates to energy metabolism and inflammation in key metabolic tissues and organs. The new findings reveal that ghrelin signaling is an important regulatory mechanism for immunometabolism and inflamm-aging. Ghrelin signaling offers an exciting novel therapeutic strategy for treatment of obesity and insulin resistance of the elderly.

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.