Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized ...clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Urolithins A and B (hydroxy-6H-dibenzob,dpyran-6-one derivatives) are colonic microflora metabolites recently proposed as biomarkers of human exposure to dietary ellagic acid derivatives. Molecular ...models suggest that urolithins could display estrogenic and/or antiestrogenic activity. To this purpose, both urolithins and other known phytoestrogens (genistein, daidzein, resveratrol, and enterolactone) were assayed to evaluate the capacity to induce cell proliferation on the estrogen-sensitive human breast cancer MCF-7 cells as well as the ability to bind to α- and β-estrogen receptors. Both urolithins A and B showed estrogenic activity in a dose-dependent manner even at high concentrations (40 μM), without antiproliferative or toxic effects, whereas the other phytoestrogens inhibited cell proliferation at high concentrations. Overall, urolithins showed weaker estrogenic activity than the other phytoestrogens. However, both urolithins displayed slightly higher antiestrogenic activity (antagonized the growth promotion effect of 17-β-estradiol in a dose-dependent manner) than the other phytoestrogens. The IC50 values for the ERα and ERβ binding assays were 0.4 and 0.75 μM for urolithin A; 20 and 11 μM for urolithin B; 3 and 0.02 for genistein; and 2.3 and 1 for daidzein, respectively; no binding was detected for resveratrol and enterolactone. Urolithins A and B entered into MCF-7 cells and were metabolized to yield mainly urolithin-sulfate derivatives. These results, together with previous studies regarding absorption and metabolism of dietary ellagitannins and ellagic acid in humans, suggest that the gut microflora metabolites urolithins are potential endocrine-disrupting molecules, which could resemble other described “enterophytoestrogens” (microflora-derived metabolites with estrogenic/antiestrogenic activity). Further research is warranted to evaluate the possible role of ellagitannins and ellagic acid as dietary “pro-phytoestrogens”. Keywords: Breast cancer; phytoestrogen; hydroxy-6H-dibenzob,dpyran-6-one derivative; endocrine-disrupting; estrogen receptor
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Twelve compounds were isolated from Winged Sumac (Rhus copallinum) fruit and their structures were elucidated on the basis of NMR and mass spectral data. The isolates included a new galloyl ...derivative, (R)-galloyl malic acid dimethyl ester (1), and eleven known compounds, gallic acid (2), methyl gallate (3), glucogallin (4), methyl m-digallate (5), methyl p-digallate (6), quercetin (7), myricetin (8), rhamnazin (9), kaempferol (10), betulinic acid (11), and oleanolic acid (12). All of the compounds were evaluated for antiproliferative effects against human colon tumorigenic (HCT-116, Caco-2) and non-tumorigenic (CCD18-Co) cell lines.
SCOPE: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from ...colorectal cancer (CRC) patients after pomegranate extract (PE) intake. METHODS AND RESULTS: CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE‐1) and high (PE‐2) punicalagin:EA ratio were administered. Twenty‐three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC‐ESI‐QTOF‐MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE‐1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE‐2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE‐2) hampered urolithins formation. CONCLUSION: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recently, the development of functional beverages has been enhanced to promote health and nutritional well-being. Thus, the fermentation of plant foods with lactic acid bacteria can enhance their ...antioxidant capacity and others like anti-inflammatory activity, which may depend on the variations in the total content and profile of (poly)phenols. The present study aimed to investigate the impact of fermentation with two strains of
of several herbal infusions from thyme, rosemary, echinacea, and pomegranate peel on the (poly)phenolic composition and whether lacto-fermentation can contribute to enhance their in vitro antioxidant and anti-inflammatory effects on human colon myofibroblast CCD18-Co cells. HPLC-MS/MS analyses revealed that fermentation increased the content of the phenolics present in all herbal infusions. In vitro analyses indicated that pomegranate infusion showed higher antioxidant and anti-inflammatory effects, followed by thyme, echinacea, and rosemary, based on the total phenolic content. After fermentation, despite increasing the content of phenolics, the antioxidant and anti-inflammatory effects via reduction pro-inflammatory markers (IL-6, IL-8 and PGE
) were similar to those of their corresponding non-fermented infusions, with the exception of a greater reduction in lacto-fermented thyme. Overall, the findings suggest that the consumption of lacto-fermented herbal infusions could be beneficial in alleviating intestinal inflammatory disorders.
Purpose
(Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of ...(poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes.
Methods
A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol.
Results
Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (− 3.32 mg/dL; 95% CI − 5.86, − 0.77;
P
= 0.011). Hb1Ac was only slightly reduced (− 0.24%; 95% CI − 0.43, − 0.044;
P
= 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (− 5.86 mg/dL, 95% CI − 11.34, − 0.39;
P
= 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (− 10.17 mg/dL, 95% CI − 16.59, − 3.75;
P
= 0.002).
Conclusions
Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Colon cancer stem cells (CSCs) offer a novel paradigm for colorectal cancer (CRC) treatment and dietary polyphenols may contribute to battle these cells. Specifically, polyphenol-derived colon ...metabolites have the potential to interact with and affect colon CSCs. We herein report the effects against colon CSCs of two mixtures of ellagitannin (ET) metabolites, ellagic acid (EA) and the gut microbiota-derived urolithins (Uro) at concentrations detected in the human colon tissues following the intake of ET-containing products (pomegranate, walnuts). These mixtures reduce phenotypic and molecular features in two models of colon CSCs: Caco-2 cells and primary tumour cells from a patient with CRC. The mixture containing mostly Uro-A (85% Uro-A, 10% Uro-C, 5% EA) was most effective at inhibiting the number and size of colonospheres and aldehyde dehydrogenase activity (ALDH, a marker of chemoresistance) whereas the mixture containing less Uro-A but IsoUro-A and Uro-B (30% Uro-A, 50% IsoUro-A, 10% Uro-B, 5% Uro-C, 5% EA) had some effects on the number and size of colonospheres but not on ALDH. These data support a role for polyphenols metabolites in the control of colon cancer chemoresistance and relapse and encourage the research on the effects of polyphenols against CSCs.
•Microbiota phenolic-derived metabolites can battle colon cancer stem cells (CSCs).•Urolithins (Uros) and ellagic acid (EA) inhibit CSC features in vitro and ex vivo.•Mixed Uros and EA inhibit the formation and growth of colonospheres.•Mixed Uros and EA reduce ALDH-expressing cell population of CSCs.•Potential effect of Uros on the recurrence and chemoresistance of colon cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Four new phenolic glycosides, saccharumosides A–D (1–4), along with eight known phenolic glycosides, were isolated from the bark of sugar maple (Acer saccharum). The structures of 1–4 were elucidated ...on the basis of spectroscopic data analysis. All compounds isolated were evaluated for cytotoxicity effects against human colon tumorigenic (HCT-116 and Caco-2) and nontumorigenic (CCD-18Co) cell lines.
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IJS, KILJ, NUK, PNG, UL, UM
We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo
...d1,3dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as (diimine)
2Ru(TSC)(PF
6)
2 (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2′-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV–Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 10
4 M
−1. They are also strong binders of human serum albumin having binding constants on the order of 10
4 M
−1. The complexes show good
in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC
50 values range from 7 to 159
μM (after 72
h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC
50 values as low as 10
μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces ...milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to overcome the mentioned RSV's drawbacks, EXOs were loaded with RSV (EXO-RSV) to evaluate its brain delivery in Sprague-Dawley rats and its in vitro antiproliferative effects against human neuroblastoma SH-SY5Y and glioblastoma U-87MG cancer cells compared with non-encapsulated RSV. Pharmacokinetic analyses in perfused brains showed RSV detection only after EXO-RSV administration, not after non-encapsulated RSV administration. Encapsulation also resulted in lower concentrations of phase II-derived RSV metabolites in circulation. Additionally, blood-brain barrier (BBB) transport assays using human brain microvascular endothelial cells (HBMECs) corroborated that encapsulation enhanced RSV transport efficiency and protected it from cellular metabolism. In vitro and in silico analyses of phase-II conjugates, primarily RSV 3-glucuronide, showed lower capacity than RSV to cross the BBB. Finally, EXO-RSV (47−750 nM) showed an increased dose-dependent antiproliferative efficacy on both cancer cell lines compared with the non-encapsulated RSV (10 μM), which was ineffective after 72 h of treatment. Our findings suggest that EXOs protect RSV from phase II metabolism and enhance its brain delivery and antiproliferative activity.
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•Milk-derived exosomes (EXO) are capable of accurately encapsulating resveratrol (RSV).•Loading EXOs with RSV boosts their delivery to the rat brain and BBB assay model.•EXOs could act as nanocarriers for RSV protecting it from phase II metabolism.•EXOs increased antiproliferative effect of RSV on neuronal SH-SY5Y and U-87MG cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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