BACKGROUND AND OBJECTIVE: Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, a product of T-helper 17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins, which have antioxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of lipopolysaccharide-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. The objectives were to determine the effects of IL-17 + cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.

MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), which is rich in proanthocyanidins, was derived from cranberry juice. Human gingival epithelial cells and normal human gingival fibroblasts were incubated with NDM (5-50 mug/mL), IL-17 (0.5-100 ng/mL), or NDM + IL-17 in serum-free medium for 6 d. IL-6 and IL-8 in culture supernatants were measured by ELISA. Membrane damage and viability were assessed by lactate dehydrogenase activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.

RESULTS: In both cell lines, IL-17 (> ~5-10 ng/mL) significantly stimulated production of IL-6 (p 0.005) and IL-8 (p 0.03). Non-toxic levels of NDM inhibited constitutive IL-6 and IL-8 production by epithelial cells (p 0.01) and fibroblasts (p 0.03) as well as IL-17-stimulated cytokine production by epithelial cells [IL-6 (maximum ~80% inhibition; p 0.0001); IL-8 (maximum ~70% inhibition; p 0.03)] and fibroblasts [IL-6 (maximum ~90% inhibition; p 0.0001); IL-8 (maximum ~80% inhibition; p 0.008)].

CONCLUSION: Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by gingival fibroblasts and epithelial cells suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

BACKGROUND: Cranberry is one of the most commonly used herbs during pregnancy. The herb has been used traditionally against urinary tract infections. No studies are found that specifically address the risk of malformations after use of cranberry during pregnancy. The aim of the study was to investigate the safety of cranberry use during pregnancy, including any effects on congenital malformations and selected pregnancy outcomes.

METHODS: The study is based on data from The Norwegian Mother and Child Cohort Study including more than 100,000 pregnancies from 1999 to 2008. Information on use of cranberry and socio-demographic factors was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30, and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway.

RESULTS: Among the 68,522 women in the study, 919 (1.3%) women had used cranberry while pregnant. We did not detect any increased risk of congenital malformations after use of cranberry. Furthermore, the use of cranberry was also not associated with increased risk for stillbirth/neonatal death, low birth weight, small for gestational age, preterm birth, low Apgar score (7), neonatal infections or maternal vaginal bleeding in early pregnancy. Although an association was found between use of cranberry in late pregnancy and vaginal bleeding after pregnancy week 17, further sub-analyses of more severe bleeding outcomes did not support a significant risk.

CONCLUSIONS: The findings of this study, revealing no increased risk of malformations nor any of the following pregnancy outcomes; stillbirth/neonatal death, preterm delivery, low birth weight, small for gestational age, low Apgar score and neonatal infections are reassuring. However, maternal vaginal bleeding should be investigated further before any firm conclusion can be drawn. Treatment guidelines on asymptomatic bacteriuria in pregnancy recommend antimicrobial therapy as the first line treatment. According to our data and the outcomes studied, cranberry does not appear to be a harmful adjunctive self-treatment.

In this study, five common proanthocyanidin purification techniques were evaluated prior to phloroglucinolysis, followed by HPLC analysis. An optimized purification method was then used to identify and quantify the proanthocyanidins (extension and terminal units of epigallocatechin, catechin, epicatechin, A type trimer, and A type dimer) of commercially available cranberry products (juices, concentrates, tablets, and capsules; n=17). Two size exclusion beads (Toyopearl 4 TSK HW-40C and Sephadex LH-20) were found suitable for proanthocyanidin purification, though proanthocyanidin extension and terminal unit composition was contingent upon the cleanup procedure utilized. These data illustrate that purification methods require consideration prior to conducting any cranberry proanthocyanidin analyses, and have to be accounted for when comparing values between studies. Total proanthocyanidin levels ranged from 11.7 (juice) to 436.4 (tablet) mg/100 mL or 100 g values obtained from Sephadex LH-20 purification, while total anthocyanin levels ranged from 0.54 (juice) to 98.00 (tablet) mg/100 mL or 100 g.

The present work proposes a new UHPLC-PDA-fluorescence method able to identify and quantify the main polyphenols present in commercial fruit juices in a 28-min chromatogram. The proposed method improve the IFU method No. 71 used to evaluate anthocyanins profiles of fruit juices. Fruit juices of strawberry, American cranberry, bilberry, sour cherry, black grape, orange, and apple, were analysed identifying 70 of their main polyphenols (23 anthocyanins, 15 flavonols, 6 hydroxybenzoic acids, 14 hydroxycinnamic acids, 4 flavanones, 2 dihydrochalcones, 4 flavan-3-ols and 2 stilbenes). One standard polyphenol of each group was used to calculate individual polyphenol concentration presents in a juice. Total amount of polyphenols in a fruit juice was estimated as total individual polyphenols (TIP). A good correlation (r(2)=0.966) was observed between calculated TIP, and total polyphenols (TP) determined by the well-known colorimetric Folin-Ciocalteu method. In this work, the higher TIP value corresponded to bilberry juice (607.324 mg/100mL fruit juice) and the lower to orange juice (32.638 mg/100mL fruit juice). This method is useful for authentication analyses and for labelling total polyphenols contents of commercial fruit juices. Copyright 2012 Elsevier Ltd. All rights reserved.

The "A-type" proanthocyanidins in cranberry fruit (Vaccinium macrocarpon Ait.) are bioactive components associated with prevention of urinary tract infections (UTI). Cranberry juice, fruit (fresh and dried), functional foods, and cranberry dietary supplements are promoted for prevention of UTI and for maintenance of urinary tract health (UTH), on the basis of their content of cranberry proanthocyanidins (c-PAC) with "A-type" interflavan bonds. With increasing consumer use of cranberries for maintenance of UTH and an expanding number of commercial cranberry products of different types, the availability of unified methods for measuring levels of c-PAC is important. This review discusses quantitative and qualitative analysis of c-PAC with "A-type" interflavan bonds in relation to their biological activity for UTI prevention. The integrity (including authenticity, standardization, efficacy, and safety) of cranberry fruit, juices, and dietary supplements may now be measured by using recent advances in mass spectrometry, liquid chromatography, production of c-PAC standards, and improved simple quantitative techniques.

BACKGROUND: Berries are known to have many kinds of biological activities. We focused on their antiviral effect, which has not yet been well evaluated.

RESULTS: We compared the anti-influenza viral effects of berries belonging to the genus Vaccinium - 35 species of blueberry (Vaccinium cyanococcus), the Natsuhaze (Vaccinium oldhamii), bilberry (Vaccinium myrtillus) and cranberry (Vaccinium oxycoccos)- with those belonging to the genus Ribes, i.e. blackcurrant (Ribes nigrum). Only Elliott and Legacy among Northern Highbush varieties but many Rabbiteye varieties such as Austin, Baldwin, Brightblue, Festival, T-100 and Tifblue showed anti-influenza viral activity. Natsuhaze, bilberry, cranberry and blackcurrant had high antiviral effects. A relationship was observed between the antiviral effect and total polyphenol content.

CONCLUSIONS: Antiviral effects were found to differ markedly between berry species. Rabbiteye varieties tended to have higher antiviral effects than Northern, Southern and Half Highbush blueberry varieties. We also found that Natsuhaze, which has recently been harvested in Japan as a potential functional food, had an antiviral effect comparable to that of bilberry, cranberry and blackcurrant. There was a positive relationship between antiviral activity and polyphenol content, indicating the possibility that polyphenol is one of the key factors in the antiviral effects of berries. 2012 Society of Chemical Industry.

Nutraceuticals are known to have numerous health and disease preventing properties. Recent studies suggest that extracts containing cranberry may have anti-aging benefits. However, little is known about whether and how cranberry by itself promotes longevity and healthspan in any organism. Here we examined the effect of a cranberry only extract on lifespan and healthspan in Caenorhabditis elegans. Supplementation of the diet with cranberry extract (CBE) increased the lifespan in C. elegans in a concentration-dependent manner. Cranberry also increased tolerance of C. elegans to heat shock, but not to oxidative stress or ultraviolet irradiation. In addition, we tested the effect of cranberry on brood size and motility and found that cranberry did not influence these behaviors. Our mechanistic studies indicated that lifespan extension induced by CBE requires the insulin/IGF signaling pathway and DAF-16. We also found that cranberry promotes longevity through osmotic stress resistant-1 (OSR-1) and one of its downstream effectors, UNC-43, but not through SEK-1, a component of the p38 MAP kinase pathway. However, SIR-2.1 and JNK signaling pathways are not required for cranberry to promote longevity. Our findings suggest that cranberry supplementation confers increased longevity and stress resistance in C. elegans through pathways modulated by daf-16 and osr-1. This study reveals the anti-aging property of widely consumed cranberry and elucidates the underpinning mechanisms.

Basic studies have proven that cranberries may prevent urinary tract infections through changing the adhesiveness of Escherichia coli (E. coli) to urothelial cells. Various cranberry preparations, including extract powder, capsules, and juice, have been shown to be effective in clinical and epidemiological research. Because cranberries are most commonly consumed as juice in a diluted concentration, the aim of this study was to investigate whether the equivalent daily dose of cranberry juice is sufficient to modify host urine to change the uropathogenicity of E. coli. Urine from rats taking an equivalent daily dose of cranberry juice has been shown to decrease the capability of E. coli in hemagglutination, urothelium adhesion, nematode killing, and biofilm formation. All these changes occurred after E. coli was incubated in cranberry metabolite-containing urine, defined as urine opsonization. Urine opsonization of E. coli resulted in 40.9% (p = 0.0038) decrease in hemagglutination ability, 66.7% (p = 0.0181) decrease in urothelium adhesiveness, 16.7% (p = 0.0004) increase in the 50% lethal time in killing nematodes, and 53.9% (p = 5.9 x 10(-4)) decrease in biofilm formation. Thus, an equivalent daily dose of cranberry juice should be considered sufficiently potent to demonstrate urine opsonization in E. coli.

Recent observational and clinical studies have raised interest in the
potential health effects of cranberry consumption, an association that
appearsto be due to the phytochemical content of this fruit. The profile of
cranberry bioactives is distinct from that of other berry fruit, being
rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present
in most other fruit. Basic research has suggested a number of potential
mechanisms of action of cranberry bioactives, although further molecular
studies are necessary. Human studies on the health effects of cranberry
products have focused principally on urinary tract and cardiovascular
health, with some attention also directed to oral health and
gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the
recurrence of urinary tract infections is important because a nutritional
approach to this condition could lower the use of antibiotic treatment
and the consequent development of resistance to these drugs. There is
encouraging, but limited, evidence of a cardioprotective effect of
cranberries mediated via actions on antioxidant capacity and lipoprotein
profiles. The mixed outcomes from clinical studies with cranberry
products could result from interventions testing a variety of products,
often uncharacterized in their composition of bioactives, using different
doses and regimens, as well as the absence of a biomarker for compliance
to the protocol. Daily consumption of a variety of fruit is necessary to
achieve a healthy dietary pattern, meet recommendations for micronutrient
intake, and promote the intake of a diversity of phytochemicals. Berry
fruit, including cranberries, represent a rich source of phenolic bioactives
that may contribute to human health.

We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.