Background: Ageing is highly associated with cognitive decline and modifiable risk factors such as diet are believed to protect against this process. Specific dietary components and in particular, (poly)phenol-rich fruits such as berries have been increasingly recognised for their protection against age-related neurodegeneration. However, the impact of cranberries on cognitive function and neural functioning in older adults remains unclear. Design: A 12-week parallel randomised placebo-controlled trial of freeze-dried cranberry powder was conducted in 60 older adults aged between 50 and 80 years. Cognitive assessment, including memory and executive function, neuroimaging and blood sample collection were conducted before and after the intervention to assess the impact of daily cranberry consumption on cognition, brain function and biomarkers of neuronal signalling. Results: Cranberry supplementation for 12 weeks was associated with improvements in visual episodic memory in aged participants when compared to placebo. Mechanisms of action may include increased regional perfusion in the right entorhinal cortex, the accumbens area and the caudate in the cranberry group. Significant decrease in low-density lipoprotein (LDL) cholesterol during the course of the intervention was also observed. No significant differences were, however, detected for BDNF levels between groups. Conclusions:The results of this study indicate that daily cranberry supplementation(equivalent to 1 small cup of cranberries) over a 12-week period improves episodicmemory performance and neural functioning, providing a basis for future investigationsto determine efficacy in the context of neurological disease.

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The immunomodulatory potential of probiotics and (poly)phenols (PP) is recognized; however, studies regarding microorganisms-PP synergisms are yet to be explored. Here, we investigated the cooperation between probiotics and berry-derived PP extracts in modulating the cytokine responses in dendritic cells. Bacteria elicited immune responses in a strain-dependent manner. PP extracts showed different modulation of cytokine triggered by bacteria. Also with LPS, used as pro-inflammatory stimulus, PP from blueberry (BB) and cranberry (CB) most efficiently reduced IL12 production. L. paracasei LPC-S01 and B. bifidum MIMBb23sg resulted the best bacterial association in abrogating IL12 and increasing IL10. The use of PP fraction from BB50f and CB1 with the LPC-S01 + MIMBb23sg association resulted the most efficient combinations in terms of anti-inflammatory activity. These results provide bases for further investigation in vivo, in the perspective to develop food supplements that might conceivably deliver the single and combined benefits of probiotics and berry (poly)phenols.

Introduction: Urinary tract infection (UTI) is a commonly acquired bacterial infection mostly in young, healthy women. Cranberry (Vaccinium macrocarpon) has historically been used for the treatment and prevention of UTIs; however, research has found conflicting evidence regarding its effectiveness for the prophylaxis of UTIs. The aim of this work is to evaluate the effectiveness of cranberry on the risk of UTI occurrences in women. Methods: A systematic review with meta-analysis of randomized controlled clinical trials (RCTs) evaluating the efficacy of cranberry as prophylaxis for recurrent UTIs in women was performed. RCTs published until January 2022 comparing any cranberry product interventions with placebo in adult women were considered eligible. All statistical analyses were conducted using the random effect model (Mantel-Haenszel method). Outcomes were reported as number of participants developing a UTI. Statistical significance was defined as P < 0.05. Results: Nine clinical trials were included in the meta-analysis. The study concluded that cranberry products reduced the risk of UTI by 21 % in women compared with the placebo group (0.79 [CI 0.67, 0.94], I2 = 47 %, P = 0.008). Subgroups, including cranberry juice encapsulated cranberry powder, cultured confirmed UTIs; asymptomatic bacteriuria and uncomplicated UTIs, were also performed. Notably, pooling data from RCTs using cranberry as tablets/capsule showed a RR = 0.71 (P = 0.005). Conclusions: This data suggested that cranberry products may be effective in the prevention of UTIs in women. However, these results are not to be considered definitive, and more clinical trials are needed to confirm these findings.

Group A Streptococci (GAS) or Streptococcus pyogenes is responsible for acute bacterial pharyngitis in children as well as adults. Streptococcal pharyngitis is initiated by successful attachment and colonization of the bacteria, followed by the establishment of the biofilm in various environments. In this study, we examined the antibacterial activities of in-house prepared aqueous and ethanolic extracts of 10 Atlantic Canada fruits in the context of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics, and adhesion inhibition properties against S. pyogenes. Per our findings, MIC and MBC for all the tested extracts ranged from 0.25 to 8 mg/mL and from 4 to 64 mg/mL, respectively. Accordingly, at 1/2 x MBC, cranberry and sumac extracts also lowered the attachment of GAS to the uncoated and fibronectin-coated substratum. Particularly, cranberry and sumac aqueous extracts were more effective against the adhesion of S. pyogenes ATCC 19615 to the fibronectin-coated surface than a clinical strain. In conclusion, ethanolic and aqueous extracts of cranberry and sumac could potentially be incorporated into natural health products designed for the amelioration of strep throat, yet a detailed understanding of its mode of action (e.g., biofilm inhibition and eradication) could pave its path to the field of antibacterial natural health product discovery, design, and development.

Numerous health benefits have been reported from the consumption of cranberry-derived products, and recent studies have identified bioactive polysaccharides and oligosaccharides from cranberry pomace. This study aimed to further characterize xyloglucan and pectic oligosaccharide structures from pectinase-treated cranberry pomace and measure the growth and short-chain fatty acid production of 86 Lactobacillus strains using a cranberry oligosaccharide fraction as the carbon source. In addition to arabino-xyloglucan structures, cranberry oligosaccharides included pectic rhamnogalacturonan I which was methyl-esterified, acetylated and contained arabino-galacto-oligosaccharide side chains and a 4,5-unsaturated function at the non-reducing end. When grown on cranberry oligosaccharides, ten Lactobacillus strains reached a final culture density (Delta OD) >= 0.50 after 24 h incubation at 32 degrees C, which was comparable to L. plantarum ATCC BAA 793. All strains produced lactic, acetic, and propionic acids, and all but three strains produced butyric acid. This study demonstrated that the ability to metabolize cranberry oligosaccharides is Lactobacillus strain specific, with some strains having the potential to be probiotics, and for the first time showed these ten strains were capable of growth on this carbon source. The novel cranberry pectic and arabino-xyloglucan oligosaccharide structures reported here combined with the Lactobacillus strains that can metabolize cranberry oligosaccharides and produce short-chain fatty acids, have excellent potential as health-promoting synbiotics.

Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 g/kg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MS/MS. The results showed that CJ significantly increased the C-max and AUC(0-t) of gefitinib by 28% and 55%, respectively. Mechanism studies indicated that CJ activated P-gp, and cranberry metabolites (CM) inhibited CYP2D6. Moreover, the protein level of P-gp in rat enterocytes was decreased, whereas that in hepatocytes was increased. In addition, the protein levels of BCRP, CYP3A4 and CYP2D6 in enterocytes and hepatocytes were decreased. In conclusion, CJ ingestion affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.

Collagens in the human skin are susceptible to glycation due to their long half-life of about 15 years, accumulating advanced glycation end products (AGEs). The formation of AGEs and the subsequent AGE-induced collagen crosslinking are major factors for skin aging. The objective of this study was to determine the capacity of cranberry juice polyphenols (CJPs) and their fractions to inhibit collagen glycation and to break AGE-induced crosslinks in collagens. Concentrated cranberry juice was extracted to obtain the CJP, which was further fractionated into an ethyl acetate fraction, water fraction, 30% methanol (MeOH) fraction, 60% MeOH fraction, MeOH fraction, and acetone fraction. CJPs and their fractions contained different ratios of anthocyanins, procyanidins, and flavonols. All the fractions significantly inhibited collagen glycation assessed with the collagen-methylglyoxal (MGO) or collagen-dehydroascorbic acid (DHAA) assays. The ethyl acetate fraction and 60% MeOH had the lowest IC50 values in the collagen-MGO and collagen-DHAA assays. The methanol fraction (IC50 = 0.52 g/mL) and acetone fraction (IC50 = 0.019 mg/mL) had the lowest IC50 values in the inhibition and breakage of AGE-induced collagen crosslinking, respectively. The ethyl acetate fraction significantly scavenged the highest amount of MGO and DHAA after incubation compared to the other fractions. Results suggested that procyanidins were the most effective antiglycation agent in both collagen glycation assays, followed by flavonols and anthocyanins. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry showed that the reactions of DHAA with quercetin or epicatechin formed several adducts with unreported proposed structures. This study suggested that CJPs may be used as active ingredients in cosmetics to prevent skin collagen glycation and crosslinking and to break the formed crosslinks.

The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of Akkermansia muciniphila, a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria Muribaculum intestinale, Faecalibaculum rodentium, Bacteroides uniformis, and Bacteroides acidifaciens. This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 (Tlr2) expression, while decreasing the expression of interleukin 1ss (ILss1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker Foxp3, while CP increased the expression of NOD-like receptor family pyrin domain containing 6 (Nlrp6) inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis.

Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one proanthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett's esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents.

Scope: The molecular basis underlying the anti-inflammatory and anticarcinogenic properties of cranberries is incompletely understood. The effects of a cranberry proanthocyanidin-rich extract (PAC) and two of its gut microbial metabolites, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl)-propionic acid (HPPA), on intestinal epithelial cells microRNA (miRNA) expression and their downstream pathways at homeostasis and in inflammatory conditions, are investigated.Methods and Results: The expression of 799 miRNAs is quantitatively assessed in differentiated Caco-2BBe1 cells pre-treated with PAC, DHPAA, or HPPA and stimulated with interleukin (IL)-1 beta or not. PAC, DHPAA, and HPPA generate subsets of shared and distinct miRNA responses. At homeostasis, miRNAs affected by the metabolites, but not PAC, targeted genes enriched in kinase, Wnt, and growth factor signaling, cell growth and proliferation, apoptosis, and specific cancer pathways. In an inflammatory environment, PAC and DHPAA, but not HPPA, reverses the expression of 16 and two IL-1 beta-induced miRNAs, respectively, regulating inflammatory and cancer pathways.Conclusion: miRNA modulation is a novel mechanism for PAC bioactivity in the gut. The gut microbiota may be necessary to unlock these effects at homeostasis and partially in inflammation.