Abstract: Urinary tract infections (UTI) are mostly caused by uropathogenic Escherichia coli (UPEC). Cranberry-based products have shown preventive effects against UTI, and this has been partially attributed to their A-type proanthocyanidin content. However, recent evidence reports phenyl- gamma -valerolactones as the most relevant urinary metabolites of cranberry procyanidins, and candidates these compounds as plausible responsible for the protective effects of cranberries against UTI. This paper studied the inhibition of the adherence of UPEC ATCCReg. 53503TM to T24 bladder epithelial cells by physiological concentrations of differently sulphated dihydroxyphenyl- gamma -valerolactones. Moreover, the transformations of these molecules in the cell media were evaluated by UHPLC-MSn. All dihydroxyphenyl- gamma -valerolactone derivatives showed anti-adhesive activity at 100 micro M, while 5-(3'-hydroxyphenyl)- gamma -valerolactone-4-O-sulphate also showed neuro-protective effects at 50 micro M. Some compounds underwent extensive metabolism during cell incubation, mainly deconjugation of sulphate moieties and opening of the lactone ring. These results shed light on the flavan-3-ol metabolites behind the prophylactic effect of cranberries against UTI.
Abstract: Commensal bifidobacteria colonize the human gastrointestinal tract and catabolize glycans that are impervious to host digestion. Accordingly, Bifidobacterium longum typically secrete acetate and lactate as fermentative endproducts. This study tested the hypothesis that B. longum utilize cranberry-derived xyloglucans in a strain-dependent manner. Interestingly, the B. longum strain that efficiently utilizes cranberry xyloglucans secrete 2.0-2.5 moles acetate:lactate. The 1.5 ratio theoretical yield obtained in hexose fermentations shifts during xyloglucan metabolism. Accordingly, this metabolic shift is characterized by increased acetate and formate production at the expense of lactate. alpha-L-arabinofuranosidase, an arabinan endo-1,5-alpha-L-arabinosidase, and a beta-xylosidase with a carbohydrate substrate-binding protein and carbohydrate ABC transporter membrane proteins are upregulated (> 2-fold change), which suggests carbon flux through this catabolic pathway. Finally, syntrophic interactions occurred with strains that utilize carbohydrate products derived from initial degradation from a heterologous bacterium.IMPORTANCE This is a study of bacterial metabolism of complex cranberry carbohydrates termed xyloglucans that are likely not digested prior to reaching the colon. This is significant as bifidobacteria interact with this dietary compound to potentially impact human host health through energy and metabolite production by bacterial utilization of these substrates. Specific bacterial strains utilize cranberry xyloglucans as a nutritive source indicating unknown mechanisms that are not universal in bifidobacteria. In addition, xyloglucan metabolism proceeds using an alternative pathway could lead to further research to investigate mechanisms underlying this interaction. Finally, we observed cross-feeding between bacteria in which one strain degrades the cranberry xyloglucan to make it available to a second strain. Similar nutritive strategies are known to occur within the gut. In aggregate, this study may lead to novel foods or supplements to impact human health through rational manipulations of their microbiome.
Abstract: The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r2=0.74, p<0.05), driven by caffeic acid 4-O- beta -D-glucuronide, quercetin-3-O- beta -D-glucuronide, ferulic acid 4-O- beta -D-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O- beta -D-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)- gamma -valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r2 >=0.89, p<0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.
Abstract: We investigated the anti-aging and redox state regulation effects by A-type proanthocyanidins (PACs)-rich cranberry concentrate (CBC) and its comparison with B-type PACs-rich grape seed extract (GSE). Using the Q-Extractive mass spectrometry, PACs dimer A and B were identified as predominant phenolic compounds of CBC and GSE, respectively, while epicatechin was present in both extracts. Using the d-galactose-induced aging mice model, effects were investigated via an 8-week oral gavage considering water-soluble vitamin E as the positive control. Both CBC and GSE reduced hepatic and brain thiobarbituric acid reactive substances, and plasma 8-isoprostane levels by 30-57%, 24-30% and 11-62%, respectively, and decreased brain and plasma monoamine oxidase activities by 27-59% and 65-71%, respectively. CBC could improve hepatic glutathione peroxidase activity by 42%, while GSE increased hepatic superoxide dismutase activity by 13%. Therefore, both extracts exerted anti-aging effects probably via regulating in vivo redox state. However, neither generated any effect on catalase activities.
Abstract: Cranberry (Vaccinium macrocarpon Aiton) is used to treat noncomplicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents able to inhibit bacterial adhesion to the urinary epithelium. However, the role of PAC-A in UTIs is debated, because of their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion, and contradictory clinical trials. The effects of 35-day cranberry supplementation (11 mg/kg PAC-A, 4 mg/kg PAC-B) were studied in healthy rats using a ultra performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach. Microbial PAC metabolites, such as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8, and 24 h after cranberry intake and their antiadhesive properties were tested against uropathogenic Escherichia coli. The 8 h samples showed the highest activity. Changes in urinary composition were studied by ultra performance liquid chromatography-time-of-flight (UPLC-QTOF), observing the presence of PAC metabolites. The PAC-A2 levels were measured in all collected samples, and the highest amounts, on the order of ng/mL, were found in the samples collected after 4 h. Results indicate that the antiadhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to a direct PAC-A effect, as the measured PAC-A levels in urine was lower than those reported as active in the literature.
Abstract: PURPOSE: We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. MATERIALS AND METHODS: This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. RESULTS: The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. CONCLUSIONS: The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms.
Abstract: An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 mug mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.
Abstract: BACKGROUND: Chlorhexidine gluconate is considered as the gold standard among various anti-plaque agents. However, many local side effects have been reported on its long term use. Cranberry (Vaccinium macrocarpon) is rich in polyphenols, including flavonoids and proanthrocyanidins. Insufficient evidences are available to support antimicrobial property of Cranberry extract mouthwash in context to red, orange and green complexes of periodontal pathogens and even comparison of same with clinically used and accepted 0.2% Chlorhexidine. MATERIALS AND METHODS: Sterilised nutrient agar plates were inoculated with suspensions of P. gingivalis, T. forsythia, P. intermedia and A. actinomycetemcomitans (overnight cultures grown at 37° on nutrient agar). The strains were allowed to grow in strict anaerobic condition. 1, 5, 10 and 15 mg/ml Cranberry extract, 0.2% Chlorhexidine and distilled water were added into wells. Plates were then again incubated at 37° for 24 hours. Diameter of zones of inhibition of all the plates was measured using digital vernier callipers. The mean score of zones of inhibition was calculated. RESULTS: Results of the study showed that all four concentrations of Cranberry extract showed comparatively less significant antimicrobial property against the microorganisms, compared to 0.2% Chlorhexidine. CONCLUSION: This study showed that 1, 5, 10 and 15 mg/ml Cranberry extract does not have significant antimicrobial efficacy against periodontopathogens, compared to that of 0.2% Chlorhexidine.
Abstract: Recent research supports a favorable role of cranberries on cardiometabolic health. Postprandial metabolism, especially hyperglycemia, has been shown to be an independent cardiovascular risk and few clinical studies have reported the role of berries in improving postprandial dysmetabolism. We investigated the postprandial effects of dried cranberries following a high-fat breakfast challenge in obese participants with type 2 diabetes (T2DM), in a randomized crossover trial. Blood draw and vascular measurements were conducted at fasting, 1, 2 and 4 hours (h), following the consumption of a fast-food style high-fat breakfast (70 g fat, 974 kcal) with or without cranberries (40 g). Analyses of our data (n = 25; BMI (kg m-2) (mean +/- s.d.) = 39.5 +/- 6.5; age (years) = 56 +/- 6) revealed that postprandial increases in glucose were significantly lower in the cranberry vs. control at 2 & 4 h (p < 0.05). No significant differences were noted in insulin, insulin resistance evaluated by homeostasis model assessment, lipid profiles and blood pressure between the cranberry and control groups. Among the biomarkers of inflammation and oxidation, postprandial serum interleukin-18 and malondialdehyde were significantly lower at 4 h, and serum total nitrite was higher at 2 h in the cranberry vs. control group (all p < 0.05). No effects were noted on C-reactive protein or interlukin-6. Overall, dietary cranberries had notable effects in improving high-fat breakfast induced postprandial glucose and selected biomarkers of inflammation and oxidation in participants with T2DM. These findings provide evidence that adding whole cranberries to a high-fat meal may improve postprandial blood glucose management and warrant further investigation.
Abstract: In this work we characterize the interaction of cranberry (Vaccinium macrocarpon) proanthocyanidins (PAC) with bovine serum albumin (BSA) and hen egg-white lysozyme (HEL) and determine the effects of these complexes on macrophage activation and antigen presentation. We isolated PAC from cranberry and complexed the isolated PAC with BSA and HEL. The properties of the PAC-protein complexes were studied by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), gel electrophoresis and zeta-potential. The effects of PAC-BSA complexes on macrophage activation were studied in RAW 264.7 macrophage like cells after treatment with lipopolysaccharide (LPS). Fluorescent microscopy was used to study endocytosis of PAC-BSA complexes. The effects of PAC complexes on macrophage antigen presentation was studied in an in vitro model of HEL antigen presentation by mouse peritoneal mononuclear cells to a T-cell hybridoma. Mass spectra of PAC complexes with BSA and HEL differed from spectra of the proteins alone by the presence of broad shoulders on the singly and doubly charged protein peaks. Complexation with PAC altered the electrophoretic mobility shift assay in native agarose gel and the electrophoretic mobility (ζ-potential) values. These results indicate that the PAC-protein complexes are stable and alter protein structure without precipitating the protein. Fluorescent microscopy showed that RAW 264.7 macrophages endocytosed BSA and PAC-BSA complexes in discrete vesicles that surrounded the nucleus. Macrophages treated with increasing amounts of PAC-BSA complexes had significantly reduced COX-2 and iNOS expression in response to treatment with lipopolysaccharide (LPS) in comparison to controls. PAC-HEL complexes modulated antigen uptake, processing and presentation in murine peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a PAC-HEL complex had already reached maximum IL-2 expression. Cranberry PAC may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas. These results suggest that PAC-protein complexes modulate aspects of innate and acquired immune responses in macrophages.
Abstract: PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed.RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.
Abstract: OBJECTIVE: To evaluate whether cranberries are able to prevent postoperative urinary bacteriuria in patients undergoing pelvic surgery and receiving transurethral catheterisation.DESIGN: Randomised, double-blind, placebo-controlled trial.SETTINGS: French tertiary Care centre, University Hospital.POPULATION: A total of 272 women undergoing pelvic surgery aged 18 or older.METHODS: Participants undergoing pelvic surgery were randomised to 36 mg cranberry (proanthocyanidins, PAC) or placebo once daily for 10 days. Statistical analysis was performed by a chi-square test.MAIN OUTCOME MEASURES: The primary and secondary outcomes were postoperative bacteriuria, defined by a positive urine culture, within the first 15 and 40 days, respectively.RESULTS: Two hundred and fifty-five participants received the intended treatment: 132 (51.8%) received PAC and 123 (48.2%) received placebo. There were no significant differences in baseline demographics, intra-operative characteristics or duration and type of catheterisation between the two groups. PAC prophylaxis did not reduce the risk of bacteriuria treatment within 15 days of surgery [27% bacteriuria with PAC compared with 25% bacteriuria with placebo: relative risk 1.05, 95% CI 0.78-1.4, P = 0.763). The same result was observed on day 40. Bacteriuria occurred more often in older women with increased length of catheterisation.CONCLUSION: Immediate postoperative prophylaxis with PAC does not reduce the risk of postoperative bacteriuria in patients receiving short-term transurethral catheterisation after pelvic surgery.
Abstract: F4+ E. coli and F18+ E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4+ E. coli and F18+ E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4+ E. coli and F18+ E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20 micro g or 100 micro g/ml) have strong inhibitory activity on F4+ E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18+ E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10 mg or 100 mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18+ E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1 g/kg or 10 g/kg). However, supplementation of feed (10 g/kg) and drinking water (1 g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18+ E. coli.
Abstract: The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic Escherichia coli was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced (P < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together (P < 0.001), and so did the combination of malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce E. coli colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents.
Abstract: BACKGROUND: Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. AIM: The aim of this study is to investigate whether intake of cranberry juice concentrate pre-operatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. DESIGN: This study employed a randomized, placebo-controlled double-blind trial. METHOD: Female patients, aged 60 years and older, with hip fracture (n=227) were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. RESULT: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39%) in the placebo group and 13 of 47 (28%) in the cranberry group (P=0.270) had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270). CONCLUSION: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and indwelling urinary catheter.
Abstract: BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.
Abstract: The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12h) state. The subjects then consumed one serving (42g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.
Abstract: Background: The aim of this study was to analyze the effect of supplementation with cranberry (Vaccinum macrocarpon) on the levels of pro-inflammatory cytokines, hepcidin and selected markers of iron metabolism in rowers subjected to exhaustive exercise. Methods: This double-blind study included 16 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n=9), receiving 1200 mg of cranberry extract for 6 weeks, or to the placebo group (n=7). The participants performed a 2000-m test on a rowing ergometer at the beginning and at the end of the preparatory camp. Blood samples were obtained from the antecubital vein prior to each exercise test, one minute after completing the test, and after a 24-h recovery period. The levels of hepcidin, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), ferritin, iron, soluble transferrin receptor (sTfR) and myoglobin were determined, along with total iron-binding capacity (TIBC), unbound iron-binding capacity (UIBC) and total antioxidant capacity (TAC). Results: Both prior and after the supplementation, a significant post-exercise increase in the concentration of IL-6 was observed in both groups. At the end of the study period, cranberry-supplemented athletes presented with significantly higher resting, post-exercise and post-recovery levels of TAC than the controls. However, a significant exercise-induced increase in the concentrations of TNF-alpha, myoglobin and hepcidin was observed solely in the control group. Conclusion: Supplementation with cranberry extract contributed to a significant strengthening of antioxidant potential in individuals exposed to strenuous physical exercise. However, supplementation did not exert direct effects on other analyzed parameters: inflammatory markers and indices of iron metabolism (TNF-alpha, hepcidin and myoglobin).
Abstract: Cranberry contains high levels of nutrients and bioactive molecules that have health-promoting properties. The purpose of the present studies was to determine if cranberry extracts (CEs) contain phytochemicals that exert anti-inflammatory effects. The human monocytic cell line THP-1 was treated with two CEs (CE and 90MX) and subsequently challenged with Lipopolysaccharides (LPS). Tumor necrosis factor alpha (TNF alpha) expression was decreased in the CE-treated cells, indicative of an anti-inflammatory effect. Gene expression microarrays identified several immune-related genes that were responsive to CEs including interferon-induced protein with tetratricopeptide repeats 1 and 3 (IFIT 1 and 3), macrophage scavenger receptor 1 (MSR1) and colony-stimulating factor 2 (CSF2). In addition, in the CE-treated cells, metallothionein 1F and other metal-responsive genes were induced. Taken together, this data indicates that CEs contain bioactive components that have anti-inflammatory effects and may protect cells from oxidative damage.
Abstract: INTRODUCTION: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370) in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was evaluated.METHODS: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489) or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney U test and Pearson's chi2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.RESULTS: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly standardized cranberry extract, while 107 of the 435 patients (24.6%) in the control group developed LUTIs (p=0.0001). A clear and significant reduction in urinary discomfort of ~50% was seen in treated subjects. The treatment also resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics. CONCLUSION: The enteric-coated, highly standardized cranberry extract could be used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic therapy in patients receiving pelvic irradiation for prostate cancer.
Abstract: BACKGROUND:The female genital apparatus, the urinary tract and the perineal supporting tissues share a common embryological origin, whose differentiation depends on the action of estrogens. In adult women, the progressive decline of the ovarian function, with the ensuing estrogen deprivation, reduces tissue tropism causing urogenital atrophy, which makes these organs much more susceptible to traumatisms and urinary infections. The disorders associated with changes in the urogenital tract of peri- and postmenopausal women have significant clinical relevance, both on account of their chronicity and high frequency of occurrence and on account of their having major repercussions on the quality of life of the women, who often have to call their doctor seeking relief for their symptoms. In general, these patients report having a significant number of episodes of cystitis per year. With a view to verifying whether the use of a new dietary supplement (Kistinox® Forte sachets) containing cranberry (Vaccinium macrocarpon), Noxamicina® (propolis extract) and D-mannose can be of use in the treatment of cystitis, with or without bacteriuria, through the elimination of urinary symptoms, a multicenter clinical study was conducted on 150 women aged 40 to 50 suffering from recurrent episodes of cystitis as attested by at least one positive urine culture during the six months preceding their recruitment.METHODS:The subjects were randomly assigned to two groups: Group A: 100 women were given Kistinox® Forte, 1 sachet per day during the first 10 days of the month, for 3 months; Group B: 50 women did not receive any treatment to serve as a control group.RESULTS:The results of the present study show a complete remission of urinary symptoms in 92 women; a slight decrease in urinary symptoms was observed in 5 subjects, whereas 3 women who stopped the treatment after the first cycle were considered drop-outs.CONCLUSIONS:This multicenter clinical study revealed the excellent efficacy and tolerability of Kistinox® Forte sachets in the treatment and prevention of urinary disorders in peri- and postmenopausal women. The posology of a sachet a day during the first 10 days of the month for 3 months was well tolerated by the patients, who did not report any disorder arising from the product.
Abstract: Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.
Abstract: The present work aims to investigate the efficacy of thermoreversible gel of cranberry juice concentrate (CJC) as local drug delivery for the treatment of periodontitis. CJC was initially tested for its antimicrobial activities like MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P. gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity (70-85%). CJC was evaluated for its biocompatibility using periodontal fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on periodontopathogen PG derived virulence factors (fimA and kgp) was studied using real time polymerase chain reaction (RT-PCR) technique wherein down regulation of selected genes demonstrated inhibitory effect against PG virulence factors. Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated for its gelation temperature, viscosity, gel strength and mucoadhesive strength. Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially available chlorhexidine gluconate gel (0.2%) using agar well diffusion demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the formulated thermoreversible gel of CJC could serve as a novel herbal alternative to currently available periodontal treatment modalities.
Abstract: OBJECTIVE:Several studies have investigated the role of cranberry extract in the prevention of recurrent urinary tract infections (UTIs), on different selected subpopulations at increased risk of UTI. In this registry, we tested the prophylactic effects of an oral supplementation containing a highly standardized cranberry extract (Anthocran®) in young subjects with a previous history of recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS:36 otherwise healthy subjects in juvenile age (between 12 and 18 years of age) suffering by recurrent UTIs were enrolled. Participants received either a standard management (SM) (control group, n=17) or SM associated with an oral daily supplementation (supplementation group, n=19). Oral supplementation consisted in one capsule containing 120 mg of cranberry extract (Anthocran®), standardized to 36 mg proanthocyanidins, for 60 days. The effectiveness in the prevention of UTIs was determined by: the number of UTIs evaluated two months before the inclusion in the registry and during the supplementation period; the number of symptom-free subjects during the registry period. Safety considerations and measurement of adherence to treatment were also performed.RESULTS:The two groups were comparable for age, gender distribution, the days of follow-up and also for the number of UTIs before inclusion. The mean number of UTIs observed during the registry in the supplemented group (0.31±0.2) was significantly lower compared to the control group (2.3±1.3) and to the mean number of UTIs assessed before inclusion (1.74±1.1) (p-value = 0.0001 for both). Moreover, 63.1% of supplemented subjects was symptom-free during the registry period, whereas 23.5% subjects were asymptomatic in the control group (p-value <0.05).CONCLUSIONS:This registry supplement study provides compelling evidence on the efficacy of an oral supplementation, based on a highly standardized cranberry extract (Anthocran®), as prophylaxis in young healthy subjects suffering by recurrent UTIs.
Abstract: Epigallocatechin gallate (EGCG) of green tea and the nutraceutical CystiCran-40 (containing 40% proanthocyanidins) of the cranberry plant have been associated with antiviral activity. The purpose of this work was to determine the mechanism of antiviral synergy between each compound. Coliphage T4II (phage T4) and the rotavirus strain SA-11(RTV) were used as model virus systems. Individual and combined flavonoids structural and molecular weight analyses were performed by NMR and HPCL/MS, respectively. A suboptimal concentration of EGCG or C-40 alone or in combination reduced phage infectivity by <=10%. Similarly, EGCG (30 micro g/ml) and C-40 (25 micro g/ml), respectively, reduced RTV titers by 3 and 13%. However, RTV titers were reduced by 32% (p < .05) with both flavonoids used in combination. RTV was not recognized in host cells by electron microscopy 24-h post-inoculation. NMR and HPLC/MS findings revealed significant structural and potential changes in molecular weight of the flavonoids in complex.
Abstract: INTRODUCTION: Hyperlipidemia, obesity, hypertension, and diabetes are the most important risk factors for cardiovascular diseases. The aim of this systematic review article is to introduce the medicinal plants that exert significant clinical effects on hypertension, hyperlipidemia, obesity, and diabetes. METHODS: In this review article, the international research databases including MEDLINE, Google scholar, EBSCO, Academic Search, Web of Science, SciVerse, Scopus (SCOPUS), EBSCO, Academic Search, Cochrane, Central Register of Controlled Trials (CENTRAL) and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched using the key words hyperlipidemia, hypertension, diabetes, herbal, obesity, and phytomedicine, matched by MESH, from their respective inceptions up to March, 2016. The plants that were effective on one, two, three, or all of four diseases were determined. The doses, side effects, the most important pharmaceutically effective compounds, the used organs, and important points regarding usage were separately recorded. Also known clinically significant interactions were presented. RESULTS: 1023 articles were found to be about medicinal plants and hypertension, 1912 articles about medicinal plants and hyperlipidemia, 810 articles about medicinal plants and obesity, 1174 articles about medicinal plants and diabetes. Of 144 plants included in the analysis, 83 were found to be effective on hyperlipidemia, 100 on hypertension, 66 on obesity, and 72 on diabetes. 43 plants were found to be effective on two diseases, 14 on three diseases, and 34 on all four diseases. Three plants (Tomato, Cranberry and Pomegranate), in food and therapeutic doses, were found to be used to treat cardiovascular diseases especially in pre-eclampsia and hyperlipidemia in pregnancy. CONCLUSION: Regarding the findings of this study, we can argue that the medicinal plants, other than monotherapy, can be used as poly-therapy, to treat cardiovascular diseases.
Abstract: Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.
Abstract: BACKGROUND: A diet rich in fruit, vegetables and juices is associated with health benefit and reduced risk of certain civilization diseases. Antioxidant properties depend mainly on the total content of polyphenols and their composition. The aim of this study was to perform a multidimensional comparative analysis of phenolic compounds of organic juices with high antioxidant capacity (chokeberry, elderberry, cranberry, pomegranate).RESULTS: All the analyzed juices were a rich source of phenolic compounds. Chokeberry juices had the highest total polyphenol content (up to 7900 mg GAE L-1 ). These juices as well as pomegranate juice were characterized by the highest antioxidant capacity (~5000 mg Trolox equivalents L-1 ). Other samples had lower total polyphenols content and total antioxidant capacity. Multidimensional analysis of the profiles of phenolic compounds showed that chokeberry juices differ from the other juices. Cranberry and pomegranate juices were similar to each other, and elderberry juice was closer to these samples than to chokeberry. The predominant polyphenols of chokeberry juices were anthocyanins (especially cyanidin-3-galactoside and cyanidin-3-arabinoside) and phenolic acids (chlorogenic and neochlorogenic acid). Elderberry juice was an exception by having flavonols (quercetin derivatives) as the principal compounds.CONCLUSION: Chokeberry juices were characterized by the highest antioxidant properties, which predispose them to further clinical research concerning the supporting cardiovascular disease prophylaxis
Abstract: 1. The aim of this study was to evaluate the role of intestinal esterases on the absorption process of tenofovir disoproxil fumarate (TDF). 2. The esterase inhibition capacity of fruit juices (FJs) rich in ester linkages and pharmaceutical excipients (having ester bonds) was performed in vitro by incubating TDF with each FJ and excipient in the intestinal washings. The ex vivo everted gut sac model was also used to evaluate the absorption enhancement capacity of these FJs and excipients. Single-dose oral pharmacokinetic studies were performed by concomitant administration of TDF with each of the selected FJs and excipients. 3. The in vitro and ex vivo studies showed that cremophor-EL and all FJs prevented the metabolism of TDF with grapefruit juice (GFJ) having the highest level of inhibition. Further, the permeability flux of the monoester form of tenofovir was increased by 113% and 212% by cranberry juice (CBJ) and GFJ, respectively. The in vivo studies also showed that both CBJ and GFJ enhanced the oral bioavailability of TDF as the AUC was increased by 24% and 97%, respectively. 4. These results indicate that the prevention of the metabolic conversion of TDF to its monoester form is crucial in increasing the oral absorption of TDF.
Abstract: CONTEXT:Cranberry has numerous biological activities, including antioxidation, anticancer, cardioprotection, as well as treatment of urinary tract infection (UTI), attributed to abundant phenolic contents.OBJECTIVE:The current study focused on the effect of cranberry juice (CJ) on blue light exposed human retinal pigment epithelial (ARPE-19) cells which mimic age-related macular degeneration (AMD).MATERIALS AND METHODS:Preliminary phytochemical and HPLC analysis, as well as total antioxidant capacity and scavenging activity of cranberry ethyl acetate extract and different CJ fractions (condensed tannins containing fraction), were evaluated. In cell line model, ARPE-19 were irradiated with blue light at 450 nm wavelength for 10 h (mimic AMD) and treated with different fractions of CJ extract at different doses (5-50 μg/mL) by assessing the cell viability or proliferation rate using MTT assay (repairing efficacy).RESULTS:Phytochemical and HPLC analysis reveals the presence of several phenolic compounds (flavonoids, proanthocyanidin, quercetin) in ethyl acetate extract and different fractions of CJ. However, the condensed tannin containing fraction of ethyl acetate extract of CJ displayed the greater (p < 0.05) scavenging activity especially at the dose of 1 mg/mL. Similarly, the condensed tannin containing fraction at 50 μg/mL presented better (p < 0.05) repairing ability (increased cell viability). Furthermore, the oligomeric condensed tannin containing fraction display the best (p < 0.05) repairing efficiency at 50 μg/mL.DISCUSSION AND CONCLUSION:In conclusion, this study distinctly proved that condensed tannin containing fraction of CJ probably exhibits better free radicals scavenging activity and thereby effectively protected the ARPE-19 cells and thus, hampers the progress of AMD.
Abstract: Wheat allergy is an IgE-mediated disorder. Polyphenols, which are known to interact with certain proteins, could be used to reduce allergic reactions. This study screened several polyphenol sources for their ability to interact with gliadins, mask epitopes, and affect basophil degranulation. Polyphenol extracts from artichoke leaves, cranberries, apples, and green tea leaves were examined. Of these extracts, the first three formed insoluble complexes with gliadins. Only the cranberry and apple extracts masked epitopes in dot blot assays using anti-gliadin IgG and IgE antibodies from patients with wheat allergies. The cranberry and artichoke extracts limited cellular degranulation by reducing mouse anti-gliadin IgE recognition. In conclusion, the cranberry extract is the most effective polyphenol source at reducing the immunogenicity and allergenicity of wheat gliadins.
Abstract: Peanut allergy is a worldwide health concern. In this study, the natural binding properties of plant-derived polyphenols to proteins was leveraged to produce stable protein-polyphenol complexes comprised of peanut proteins and cranberry (Vaccinium macrocarpon Ait.) or lowbush blueberry (Vaccinium angustifolium Ait.) pomace polyphenols. Protein-bound and free polyphenols were characterized and quantified by multistep extraction of polyphenols from protein-polyphenol complexes. Immunoblotting was performed with peanut-allergic plasma to determine peanut protein-specific IgE binding to unmodified peanut protein, or to peanut protein-polyphenol complexes. In an allergen model system, RBL-2H3 mast cells were exposed to peanut protein-polyphenol complexes and evaluated for their inhibitory activity on ionomycin-induced degranulation ( beta -hexosaminidase and histamine). Among the evaluated polyphenolic compounds from protein-polyphenol complex eluates, quercetin, - in aglycone or glycosidic form - was the main phytochemical identified to be covalently bound to peanut proteins. Peanut protein-bound cranberry and blueberry polyphenols significantly decreased IgE binding to peanut proteins at p<0.05 (38% and 31% decrease, respectively). Sensitized RBL-2H3 cells challenged with antigen and ionomycin in the presence of protein-cranberry and blueberry polyphenol complexes showed a significant (p<0.05) reduction in histamine and beta -hexosaminidase release (histamine: 65.5% and 65.8% decrease; beta -hexosaminidase: 60.7% and 45.4% decrease, respectively). The modification of peanut proteins with cranberry or blueberry polyphenols led to the formation of peanut protein-polyphenol complexes with significantly reduced allergenic potential. Future trials are warranted to investigate the immunomodulatory mechanisms of these protein-polyphenol complexes and the role of quercetin in their hypoallergenic potential.
Abstract: 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.
Abstract: Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human.
Abstract: Breast cancer is the most common cancer and a major cause of death in women. The present study was designed to evaluate the antioxidant and anticancer potential of cranberry extract against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in rats. The tumor was induced in Female virgin rats of age 50 days by single dose of MNU (50mg/kg.b.w i.p.). After 85 days; all rats developed at least one tumor. Animals were treated with cranberry extract (400 and 600 mg/kg.b.w.orally) and tamoxifen (2mg/kg.b.w. i.p) for 4 weeks (from day 86 to day 113). MNU treatment resulted in a significant decrease (p < 0.05) in blood hemoglobin (Hb), red blood cells (RBC), platelets (PLTs) as well as blood, liver and breast catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MNU treatment resulted in a significant increase in White blood cells (WBC) as well as plasma, liver and mammary tissue gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), hexosamine, sialic acid and thiobarbituric acid reactive substances (TBARs). Upon administration of the cranberry extract, the levels of WBC, GGT, LDH, hexosamine, sialic acid, TBARs, Hb, RBC, PLTs, CAT, GPx and SOD were significantly normalized. Histopathological changes also confirmed the formation of tumor tubules and neovascularization after the MNU treatment. Cranberry extract administration significantly reduces the growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development. Comparing the beneficial effect of cranberry extract with that of MNU-induced breast cancer, cranberry extract showed antitumor and antioxidant activity indicated by the measured biochemical parameters and the histopathological examination of mammary tissue. The results of the present study indicate that cranberry extract possesses strong anticancer effects through its role in modulating glycoprotein components and the levels of oxidative stress biomarkers. Cranberry exerted a stronger anticancer effect at the dosage of 600 mg/kg body weight than at dosage 400 mg/kg body weight.
Abstract: Background: Cranberry pomace (CP), an underutilized by-product from juice processing, contains a wide range of biologically active compounds that can be recovered and used in a variety of applications in functional foods and nutraceuticals. Methods: In this study, analytical chemical techniques such as solvent extractions and characterization of extracts in respect with their phenolic content were performed using ultra-high performance liquid chromatography mass spectrometry (UPLC-MS) and spectrophotometry. Crude CP extract and its phenolic acids, flavonols, anthocyanins and proanthocyanidins–rich fractions were then evaluated for their anti-oxidant capacity, tyrosinase inhibitory activity, and anti-proliferation activity against hepatocellular carcinoma HepG2 cells. Results: On a dry weight basis, the different CP fractions contained seven major anthocyanins (0.1-125 mg/g), six major phenolic acids (0.8-31 mg/g), seven flavonols (1-126 mg/g) and five flavan-3-ols (0.1-12 mg/g). Fractions rich in flavonols exhibited the most potent antioxidant capacities with ferric ion reducing antioxidant power values of 1.8-1.9 mmole/g and 2, 2-diphenyl-1-picrylhydrazyl radical scavenging IC50 values of 15.1-15.2 mg/L respectively. On the other hand, fractions rich in phenolic acids and flavan-3-ol monomers demonstrated the most potent anti-tyrosinase activity (IC50=6.1-6.2 mg/L) and anti-proliferative activity (IC50=7.8-15.8 mg/L). Generally, all the fractions exhibited a dose-response relationship in the selected biological activity assays.Conclusion: This study suggests an effective utilization of CP to obtain biologically active fractions with potential to be used in functional foods and nutraceuticals designed for the prevention of chronic diseases associated with oxidative stress.
Abstract: Cranberries and probiotics are individually considered as functional foods. This study evaluated the potential synergy between bioactive proanthocyanidins (c-PAC) derived from cranberries and probiotics on reducing the invasiveness of extra-intestinal pathogenic Escherichia coli (ExPEC) in a cell culture model. ExPEC can be a component of the gut microbiota in healthy individuals, and reducing the invasiveness of ExPEC is a potential means to lessen the risk of subsequent urinary tract infections (UTI), the most common bacterial infections in women. c-PAC (>92% A-type) concentrations greater than 36 micro g c-PAC/mL significantly (p<0.05) reduced ExPEC invasion, and was not inhibited by the presence of probiotics. Scanning electron microscopy suggests that the mechanism by which c-PAC prevent ExPEC invasion is by cross-linking surface virulence factors. A probiotic blend also significantly reduced invasion, albeit via a different mechanism. This study demonstrated the potential benefit of combining functional A-type c-PAC components in cranberry foods with probiotics.
Abstract: Background: Catheter-associated urinary tract infections (CAUTIs) represent over 30% of hospital-acquired infections with an annual incidence of 560,000 CAUTIs per year in the United States. An estimated 13,000 deaths are attributable to CAUTIs annually. Standard prevention strategies frequently fail to eliminate CAUTI in intensive care units. The effectiveness of a hospital-based program of cranberry products (CP) and meatal antimicrobials to prevent CAUTI in a heterogeneous ICU population has not been evaluated. Methods: Data of Foley days and incidence of CAUTI in the Critical Care Unit (CCU) and the general wards (GW) in a single 245-bed suburban medical center were collected as a part of routine infection control surveillance. Standard CAUTI prevention bundles were applied throughout the hospital in 2009. In May 2012 an intervention of applying Bacitracin ointment to the urinary meatus-Foley junction and oral cranberry juice or tablets was started only in the CCU. A retrospective review of the data collected before and after the intervention in both the GW and CCU was completed. Results: Prior to the QI intervention in May 2012, average CAUTI rates were 2.8 CAUTIs per 1000 catheter days (CI 0.26-1.89) in the CCU and 1.6 CAUTIs per 1000 catheter days (CI 0.71-4.97) on the GW (p = 0.28). After the intervention, the average number of CAUTIs/1000 days in the CCU was 0, which was significantly different from the average of 1.52 CAUTIs/1000 days (CI 0.78-2.26) on the GW (p < 0.001). Conclusion: Our data indicate that the addition of cranberry-containing products and antimicrobial meatal care may further reduce incidence of CAUTI when added to standard recommendations. Further research will be necessary to determine if these interventions could be effective in a wider population.
Abstract: Cranberry products have long been used to treat urinary tract infections. It is believed that the A-type proanthocyanidins in cranberries contribute to this function. Peanut is one of the other, few food sources that primarily contain A-type proanthocyanidins. The skin on the outside of the peanut kernels (testa), which is treated as an agriculture waste product, contains high levels of A-type proanthocyanidins. In this study, an HPLC diol column separation method and MALDI-TOF MS were used to characterize and compare the proanthocyanidin compositions of peanut skins and cranberries. MALDI-TOF MS in linear mode was able to detect a group of proanthocyanidins with DP (degree of polymerization) 10 in peanut skin extract, but was only able to detect DP 8 in cranberry extract.The reflectron mode showed clusters of clear narrow peaks at DP 7 in peanut skin extract, while the highest DP resolved for cranberry extract was only 3 in reflectron mode. This might be due to the low response intensity of the cranberry samples with the current cleanup method and the matrix. Based on the resolved peaks in reflectron mode, peanut skins and cranberries have similar proanthocyanidins composition; they contain both A-type and B-type proanthocyanidins, with the A-type being predominant. This result may inspire future studies on the comparison of biological functions between peanut skins and cranberries and further comparison of their polymeric proanthocyanidin composition.
Abstract: Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.
Abstract: Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Nonalcoholic fatty liver disease (NAFLD) is a comorbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat (HF)-fed obese C57BL/6J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE-supplemented mice compared to HF-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to HF-fed controls. Hepatic protein levels of tumor necrosis factor alpha and C-C chemokine ligand 2 were reduced by 28% and 19%, respectively, following CBE supplementation. CBE significantly decreased hepatic mRNA levels of toll-like receptor 4 (TLR4, 63%) and nuclear factor kappa B (NF kappa B, 24%), as well as a number of genes related to the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 inflammasome. In conclusion, CBE reduced NAFLD and hepatic inflammation in HF-fed obese C57BL/6J mice. These effects appear to be related to mitigation of TLR4-NF kappa B related signaling; however, further studies into the underlying mechanisms of these hepatoprotective effects are needed.
Abstract: A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans. In this article, we report that supplementation of this cranberry extract delayed A beta toxicity-triggered body paralysis in the C. elegans AD model. Genetic analyses indicated that the cranberry-mediated A beta toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C. elegans against A beta toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated A beta toxicity in C. elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.
Abstract: Background and Objectives. Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Conclusions: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.
Abstract: Background: Due to the higher susceptibility of metabolic syndrome (MS)-afflicted patients to different metabolic abnormalities, treatment programs are vital parts of MS management. One of the possible adjunctive therapies is taking cranberry supplements as important sources of polyphenols that bear antioxidative and health-promoting properties.Objectives: The aim of this study was to evaluate the effect of cranberry extract on some components of metabolic syndrome.Patients and Methods: In a randomized, double-blind placebo-controlled clinical trial, 48 obese and overweight females diagnosed with MS were assigned into two groups to receive cranberry supplement or placebo for an eight-week period. Serum glucose, lipoproteins, inflammatory markers and blood pressure were evaluated at the baseline and at the end of the treatment phase.Results: Cranberry supplements had no effect on any of the variables including glucose, insulin, malondialdehyde (MDA), high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and blood pressure, except for high-density lipoprotein cholesterol (HDL-c), which significantly increased (P < 0.05) at the eighth-week period compared with the placebo samples.Conclusions: The results of the present study revealed that cranberry supplement might only ameliorate low HDL-c as a component of metabolic syndrome, and not the other risk factors of MS.
Abstract: Anthocyanins are a group of widespread natural phenolic compounds in vegetables and fruits. The anthocyanins have a wide range of applications due to the antioxidant, anticancer and anti-inflammatory properties. In this study, anthocyanins (delphinidin-3-o-glucoside, cyanidin-3-o-glucoside, pelargonidin-3-o-glucoside and malvidin-3-o-glucoside) in cherry and cranberry were determined using high-performance liquid chromatography–electrospray ionization–mass spectrometry (HPLC–ESI–MS). The anthocyanins were separated using gradient elution and a reserved-phase analytical column before identification by high-performance liquid chromatography–electrospray ionization–mass spectrometry. A high-performance liquid chromatography–electrospray ionization–mass spectrometry method was optimized for the determination of anthocyanins in cherry and cranberry. Furthermore, in this study, we investigated extraction conditions of fruit samples as well as determination of optimum HPLC–ESI–MS conditions. This study is novel in terms of simultaneously examining both optimization of HPLC parameters and extraction conditions. Obtained optimum conditions were used for the determination as the quantitative and qualitative analysis of anthocyanins in cherry and cranberry. The content of anthocyanins on the basis of wet weight in cherry and cranberry samples was determined for delphinidin-3-o-glucoside <d.l. (detection limit) and <d.l., for cyanidin-3-o-glucoside varied from 3.5 ± 0.4 to 8.3 ± 1.1 mg kg−1 (average 5.8 ± 0.8 mg kg−1) and 9.8 ± 1.4 to 18 ± 3.0 mg kg−1 (average 13.2 ± 1.8 mg kg−1), for pelargonidin-3-o-glucoside <d.l. and varied from 136 ± 19 to 233 ± 35 mg kg−1 (average 185.3 ± 28 mg kg−1), for malvidin-3-o-glucoside <d.l. and <d.l., respectively.
Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes.Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective:To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes.Design, Setting, and Participants:Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015).Interventions:Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants.Main Outcomes and Measures:Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration.Results:Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25).Conclusions and Relevance:Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year.Trial Registration:clinicaltrials.gov Identifier: NCT01691430.
Please see this link for the Cranberry Institute's official statement regarding this research: http://www.cranberryinstitute.org/HCP/cranutiresponse.html
Abstract: In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 micro M. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 micro M) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.
Abstract: The intestinal absorption of bacterial lipopolysaccharide (LPS) and dietary fat has been implicated in the development of metabolic endotoxemia. This study first compared the ability of polyphenol extracts from grape, cranberry, avocado and apple to interfere with pancreatic lipase and LPS in vitro. The grape extract displayed a higher inhibitory activity of lipase (IC50=8.6+or-1.1 mg/ml) and LPS binding (IC50=90+or-1.1 micro g/ml). Then, a study was carried out in 12 normal weight and 17 overweight/obese subjects to determine the effect of this extract on the postprandial changes in plasma triacylglycerols, LPS and IL-6. The presence of small intestine bacterial overgrowth (SIBO), in which higher levels of bacteria and eventually LPS are present in the upper intestine, i.e. where dietary fat absorption occurs, was also evaluated. Compared with placebo, the grape extract did not affect postprandial triacylglycerolemia but decreased plasma LPS, without affecting the IL-6-associated inflammatory response. SIBO did not affect these variables.
Abstract: Drinking of cranberry fruit juice and application of commercial preparations containing the cranberry extracts are recommended in the prevention and treatment of urinary tract infections (UTIs), especially in women with recurrent UTIs. Many studies focus on the activity of cranberries against uropathogenic Escherichia coli (E. coli) strains. However, the knowledge of the cranberry effect on Gram-positive Enterococcus faecalis (E. faecalis) is limited. Therefore, the aim of our study was to establish the activity of commercial concentrated cranberry extract on the growth, virulence factors and biofilm formation of E. faecalis strains isolated from urine. Minimal inhibitory concentrations (MICs) of cranberry extract were determined by the broth microdilution method. Disc diffusion method was used to determine antimicrobial susceptibility. The impact of cranberry extract on bacterial survival, hydrophobicity, synthesis of lipase, lecithinase, DNase, hemolysin, gelatinase and biofilm mass was determined. Results show that cranberry extract inhibits the growth, enzymatic activities of bacteria and limits biofilm formation. The antibacterial activities of the studied cranberry extract confirm that it could be successfully used in prevention of UTIs caused by E. faecalis.
Abstract: OBJECTIVE: Recently, cranberry extracts have been tested as a nutritional supplementation in the prevention of lower urinary tract symptoms (LUTS) as well as recurrent urinary tract infections (UTIs) in subjects at risk, with mixed results. However, evidence of efficacy should be considered only for well-characterized and standardized products in a more selected study population. Moreover, the efficacy of these interventions in elderly must be further investigated. The aim of this pilot, registry study was to evaluate the prophylactic effects of an oral supplementation containing a highly concentrated and standardized cranberry extract reproducing the natural total profile of cranberry fruits, in elderly men with benign prostatic hyperplasia (BPH), suffering from recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS: 43 men (age > 65 years) enrolled in this study freely decided to receive either a standard management (SM) only (n = 21) or SM associated with an oral supplementation (n = 23). Supplementation consisted in a daily administration of one capsule containing cranberry extract (Anthocran®) for 60 consecutive days. The clinical effectiveness in the prevention of UTIs was determined by the number of UTIs in the two months before the inclusion in the registry and during the supplementation period, and the number of symptom-free subjects during the registry period. Safety considerations were also performed.RESULTS: In the supplemented group, the mean number of UTI episodes reported during the registry (0.8 ± 0.5) significantly decreased compared with inclusion time (3.2 ± 1.3), p-value = 0.0001. No significant changes were observed in control, SM-only group. Importantly, the cranberry oral supplementation was superior over SM at reducing the mean number of UTIs (p-value = 0.0062).CONCLUSIONS: These results suggest that cranberry supplementation could be an effective and safe approach, within an SM program, for the prevention of recurrent UTIs in elderly men suffering from BPH avoiding some antibiotic treatments.
Abstract: Ultrahigh pressure liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry (UHPLC-APPI-MS/MS) was applied to the analysis and authentication of fruit-based products and pharmaceutical preparations. Two sub-2 micro m C18 reversed-phase columns, Syncronis (100x2.1 mm, 1.7 micro m) and Hypersil Gold (50x2.1 mm, 1.9 micro m), were proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 29 polyphenols, allowing us to obtain polyphenolic profiles in less than 13.5 and 23.5 min, respectively. Several atmospheric pressure ionization (API) sources (H-ESI, APCI, and APPI) were compared. For dopant-assisted APPI, four organic solvents, toluene, acetone, chlorobenzene and anisole, were evaluated as dopants. Both H-ESI and acetone-assisted APPI were selected as the best ionization sources for the analysis of targeted polyphenols. Acceptable sensitivity (LOD values down to 0.5 micro g kg-1 in the best of cases), linearity (r2 higher than 0.995) and good precision (RSD values lower than 15.1%) and trueness (relative errors lower than 10.2%) were obtained using both UHPLC-API-MS/MS methods. A simple extraction procedure, consisting of sample sonication with acetone/water/hydrochloric acid (70:29.9:0.1 v/v/v) and centrifugation, was used. The proposed UHPLC-ESI-MS/MS and UHPLC-APPI-MS/MS methods with both C18 reversed-phase columns were then applied to the analysis of 32 grape-based and cranberry-based natural products and pharmaceutical preparations. Polyphenolic profile data were then analyzed by principal component analysis (PCA) to extract information on the most significant data contributing to the classification of natural extracts according to the type of fruit.
Abstract: Cranberry is reported to have health benefits, including prevention of urinary tract infections and other chronic diseases, due to the high content of polyphenols, including flavonols and flavan-3-ols. The aim of this study was to determine the clearance of flavonol glycosides and flavan-3-ols and/or their metabolites in human urine. Ten healthy women volunteers ingested 240 mL of cranberry juice containing flavonol glycosides. Urine samples were collected at 0, 90, 225, and 360 min postingestion. While flavan-3-ols were not detected, five flavonol glycosides common in cranberry were identified. Quercetin-3-galactoside, the most abundant cranberry flavonol, exhibited the highest peak urine concentration (Cmax) of 1315 pg/mg creatinine, followed by quercetin-3-rhamnoside, quercetin-3-arabinoside, myricetin-3-arabinoside, and myricetin-3-galactoside. Quercetin-3-arabinoside showed delayed clearance, Cmax at 237 min (Tmax), relative to other flavonols (90-151 min). Both aglycone and the conjugated sugar moiety structure mediate the flavonol's bioavailability. Interindividual variation for bioavailability and clearance is also apparent. Metabolites, e.g. glucoronides, were not detected.