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Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. This study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no significant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM-free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM-delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice., Methods: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200 mg/kg, Chow + CE, HFHS + CE) or vehicle (Chow, HFHS) for 8 additional weeks., Results: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS + CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARα) and downregulation of several pro-inflammatory genes (eg, COX2, TNFα) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS + CE mice. The gut microbiota of HFHS + CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls., Conclusions: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols., (Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

No effective preventive treatment is available for age-related cognitive decline and Alzheimer's disease (AD). Epidemiological studies indicate that a diet rich in fruit is associated with cognitive improvement. It was thus proposed that high polyphenol concentrations found in berries can prevent cognitive impairment associated with aging and AD. Therefore, the Neurophenols project aimed at investigating the effects of a polyphenolic extract from blueberries and grapes (PEBG) in the triple-transgenic (3xTg-AD) mouse model of AD, which develops AD neuropathological markers, including amyloid-β plaques and neurofibrillary tangles, leading to memory deficits. In this study, 12-month-old 3xTg-AD and NonTg mice were fed a diet supplemented with standardized PEBG (500 or 2500 mg/kg) for 4 months (n = 15-20/group). A cognitive evaluation with the novel object recognition test was performed at 15 months of age and mice were sacrificed at 16 months of age. We observed that PEBG supplementation with doses of 500 or 2500 mg/kg prevented the decrease in novel object recognition observed in both 15-month-old 3xTg-AD mice and NonTg mice fed a control diet. Although PEBG treatment did not reduce Aβ and tau pathologies, it prevented the decrease in mature BDNF observed in 16-month-old 3xTg-AD mice. Finally, plasma concentrations of phenolic metabolites, such as dihydroxyphenyl valerolactone, a microbial metabolite of epicatechin, positively correlated with memory performances in supplemented mice. The improvement in object recognition observed in 3xTg-AD mice after PEBG administration supports the consumption of polyphenols-rich extracts to prevent memory impairment associated with age-related disease, without significant effects on classical AD neuropathology.

Blueberries contain significant amounts of flavonoids to which a number of beneficial health effects in humans have been associated. The present study investigated the effect of a polyphenol-rich lowbush blueberry (Vaccinium angustifolium Ait.) extract on the two main etiologic components of periodontitis, a multifactorial disorder affecting the supporting structures of the teeth. Phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols), and procyanidins made up 16.6, 12.9, and 2.7% of the blueberry extract, respectively. The blueberry extract showed antibacterial activity (MIC = 1 mg/mL) against the periodontopathogenic bacterium Fusobacterium nucleatum. This property may result from the ability of blueberry polyphenols to chelate iron. Moreover, the blueberry extract at 62.5 μg/mL inhibited F. nucleatum biofilm formation by 87.5 ± 2.3%. Subsequently, the ability of the blueberry extract to inhibit the NF-κB signaling pathway in U937-3xκB cells was investigated. The blueberry extract dose-dependently inhibited the activation of NF-κB induced by F. nucleatum. In addition, a pretreatment of macrophages with the blueberry extract (62.5 μg/mL) inhibited the secretion of IL-1β, TNF-α, and IL-6 by 87.3 ± 1.3, 80.7 ± 5.6, and 28.2 ± 9.3%, respectively, following a stimulation with F. nucleatum. Similarly, the secretion of MMP-8 and MMP-9 was also dose-dependently inhibited. This dual antibacterial and anti-inflammatory action of lowbush blueberry polyphenols suggests that they may be promising candidates for novel therapeutic agents.

Unlabelled: Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body's natural defenses against inflammatory diseases., Hypothesis: To define the polyphenols extracted from dried apple peels (DAPP) and determine their antioxidant and anti-inflammatory potential in the intestine. Caco-2/15 cells were used to study the role of DAPP preventive actions against oxidative stress (OxS) and inflammation induced by iron-ascorbate (Fe/Asc) and lipopolysaccharide (LPS), respectively., Results: The combination of HPLC with fluorescence detection, HPLC-ESI-MS TOF and UPLC-ESI-MS/MS QQQ allowed us to characterize the phenolic compounds present in the DAPP (phenolic acids, flavonol glycosides, flavan-3-ols, procyanidins). The addition of Fe/Asc to Caco-2/15 cells induced OxS as demonstrated by the rise in malondialdehyde, depletion of n-3 polyunsaturated fatty acids, and alterations in the activity of endogenous antioxidants (SOD, GPx, G-Red). However, preincubation with DAPP prevented Fe/Asc-mediated lipid peroxidation and counteracted LPS-mediated inflammation as evidenced by the down-regulation of cytokines (TNF-α and IL-6), and prostaglandin E2. The mechanisms of action triggered by DAPP induced also a down-regulation of cyclooxygenase-2 and nuclear factor-κB, respectively. These actions were accompanied by the induction of Nrf2 (orchestrating cellular antioxidant defenses and maintaining redox homeostasis), and PGC-1α (the "master controller" of mitochondrial biogenesis)., Conclusion: Our findings provide evidence of the capacity of DAPP to reduce OxS and inflammation, two pivotal processes involved in inflammatory bowel diseases.