Background: The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs). Methods: In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. Results: After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P=.02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E. coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E. coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E. coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated. Conclusion: In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance.

Berries have been recognized as a functional food with potential to protect against a variety of health conditions, including some cancers. Cranberry (Vaccinium macrocarpon) production and consumption have grown in recent years, warranting further evaluation of potential health benefits. Extracts and isolated constituents from cranberry fruit inhibit growth and proliferation of tumor cells in vitro, and recent data from animal studies lend further support to cranberry's reputation as a cancer fighter. Several likely mechanisms of action for cranberry against prostate and other cancers have been identified, including induction of apoptosis and inhibition of events linked to cellular invasion and migration. This article attempts to put into perspective what is known about cranberry's potential chemopreventive properties, what is yet to be determined, and some factors to consider as research moves forward.

Urinary tract infections (UTI) are common in childhood. In 30-50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), neurogenic bladder (NB), previous cystitis or pyelonephritis and malformative uropathies. To reduce the likelihood of UTI, antibiotic prophylaxis has been regarded as the therapeutic standard for many years. However, the disadvantage of long-term antibiotic therapy is the potential for development of collateral effects and resistant organisms in the host. Such reasons have induced scientists to search for alternative modalities of UTI prevention and have contributed to determining the increasing desire for "naturalness" of the population and preventing excessive medication. The use of cranberry fulfils these needs by potentially replacing or enhancing traditional procedures. The purpose of this study was to assess the effectiveness of cranberry in preventing UTI in pediatric populations. We searched Pubmed, the Cochrane Central Register of Controlled Trials and Internet. Cranberry in patients with previous UTI was evaluated in three studies, cranberry in patients with VUR in three studies and four studies analyzed the efficacy of cranberry in children with NB. In seven of nine studies cranberry had a significant effect in preventing UTI.

Protein glycation caused by sugars and reactive carbonyls is a contributing factor to diabetic complications, aging, and other chronic diseases. The objective of this study was to investigate the inhibitory effects of cranberry phytochemicals on protein glycation. Cranberries, purified to yield sugar-free phytochemical powder, were fractionated into ethyl acetate and water fractions. Water fraction was further separated into water fraction I, II, and III on a Sephadex LH-20 column. Cranberry phytochemical powder and its fractions significantly inhibited the formation of glycated hemoglobin. The concentrations of cranberry phytochemicals required to inhibit 50% of albumin glycation (EC(50)) in albumin-glucose assay were lower than that of aminoguanidine except for water fraction I. Cranberry phytochemicals inhibited glycation of human serum albumin mediated by methylglyoxal, but the EC(50) were higher than that of aminoguanidine. Carbonyl scavenging assay showed that water fraction II scavenged 89.3% of methylglyoxal at 6 h of reaction. Fractions enriched with procyanidins showed higher antiglycation activities, suggesting procyanidins were the major active components. The hypothesis whether cranberry procyanidins scavenged reactive carbonyls by forming adducts was tested. Epicatechin was used as a model compound to react with methylglyoxal and glyoxal at pH 7.4. Five adducts were detected and their structures were tentatively identified using HPLC-ESI-MS/MS.

Cranberries are rich in bioactive constituents purported to enhance immune function, improve urinary tract health, reduce cardiovascular disease and more recently, inhibit cancer in preclinical models. However, identification of the cranberry constituents with the strongest cancer inhibitory potential and the mechanism associated with cancer inhibition by cranberries remains to be elucidated. This study investigated the ability of a proanthocyanidin rich cranberry fraction (PAC) to alter gene expression, induce apoptosis and impact the cell cycle machinery of human NCI-H460 lung cancer cells. Lung cancer is the leading cause of cancer-related deaths in the United States and five year survival rates remain poor at 16%. Thus, assessing potential inhibitors of lung cancer-linked signaling pathways is an active area of investigation.

The glycosides of flavonoid, anthocyanins and A type proanthocyanidins in cranberry concentrate were characterized and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cranberry concentrate (1 g/body weight) was orally gavaged to Fischer-344 rats (n = 6), and blood and urine samples were collected over 24 h periods. Quercetin, 3'-O-methylquercetin (isorhamnetin), myricetin, kaempferol, and proanthocyanidin dimer A2, together with thirteen conjugated metabolites of quercetin and methylquercetin and intact peonidin 3-O-galactoside and cyanidin 3-O-galactoside were identified in the rat urine after cranberry treatment. Very low levels of isorhamnetin (0.48 +/- 0.09 ng/mL) and proanthocyanidin dimer A2 (0.541 +/- 0.10 ng/mL) were found in plasma samples after 1 h of cranberry administration. Although no quercetin was detected in plasma, MRM analysis of the methanolic extract of urinary bladder showed that chronic administration of cranberry concentrate to rats resulted in accumulation of quercetin and isorhamnetin in the bladder. These results demonstrate that cranberry components undergo rapid metabolism and elimination into the urine of rats and are present in the urinary bladder tissue potentially allowing them to inhibit urinary bladder carcinogenesis.

The effect of cranberry extracts and juices during cranberry juice processing on the antiproliferative properties against colon cancer cells was investigated. Two colon cancer cell lines HT-29 and LS-513 were treated with different concentrations of cranberry phenolic extracts from fruits, puree, depectinised puree and pomace and different concentration of three juices (raw, filtered and concentrated juices). The phenolic extracts consisted of water-soluble phenolic compounds, apolar phenolic compounds and anthocyanins. These phenolic extracts and juices were tested against two cell lines at pH 2.5 (natural
juice pH) and at pH 7.0 (physiological pH). All cranberry extracts and juices could inhibit the growth of both cell lines with the IC50 values (the concentration of phenolic content required to inhibit 50% the growth of cancer cells) varied from 3.8 to 179.2 lg gallic acid equivalent/ml. It was found that three types of extracts from fruit at pH 7.0 were the most effective at inhibiting the growth of HT-29 cell line. Extracts containing anthocyanins from fruit and from pomace were the most and the least efficient, respectively, in inhibiting the growth of both cancer cell lines. Further, three juices at natural pH (pH 2.5) were more effective at inhibiting the growth of two cell lines as compared to juices at pH 7.0. Concentrated juice at both pH values was the most effective at growth inhibition of two cancer cell lines compared to two other juices.

This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 microg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 microg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 microg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

Cranberry extracts may provide beneficial health effects in the treatment of various diseases, including cancer. However, the underlying molecular mechanisms of antineoplastic properties are not understood. We report the effect of a proanthocyanidin (PAC)-rich isolate from cranberry (PAC-1) as a therapeutic agent with dual activity to target both ovarian cancer viability and angiogenesis in vitro. PAC-1 treatment of chemotherapy-resistant SKOV-3 cells blocked cell cycle progression through the G2/M phase, increased the generation of reactive oxygen species (ROS), and induced apoptosis through activation of intrinsic and extrinsic pathway components. Cytotoxicity of PAC-1 was partially based on ROS generation and could be blocked by co-treatment with antioxidant glutathione. PAC-1 reduced the cell viability of both SKOV-3 ovarian cancer cells and HUVEC endothelial cells in a dose-dependent manner and blocked the activation of the pro-survival factor AKT. Furthermore, PAC-1 blocked vascular endothelial growth factor (VEGF)-stimulated receptor phosphorylation in endothelial cells, which correlated with the inhibition of endothelial tube formation in vitro. Our findings suggest that PAC-1 exerts potent anticancer and anti-angiogenic properties and that highly purified PAC from cranberry can be further developed to treat ovarian cancer in combinational or single-agent therapy.

Plant material screening was performed to study anti-Helicobacter pylori activity in vitro using an agar diffusion method on Columbia blood agar. 33 substances, juices and plant extracts and 35 of their combinations were tested. Quince (Cydonia oblonga) juice demonstrated the strongest anti-H. pylori activity followed by cranberry juice. Concentrated apple juice, plum, red currant, black chokeberry, raspberry and bilberry juice also showed significant activity. Green tea and apple pomace extract as well as sweet flag rhizome, ginger and wild bergamot extract, cherry syrup, red beet juice and whey did not exhibit anti-Helicobacter activity. Quince juice in combination with bilberry, black chokeberry, red currant juice, green tea, sweet flag rhizome or apple pomace extract as well as cranberry juice in combination with sweet flag rhizome extract demonstrated a synergistic effect on inhibition of H. pylori. The obtained results offer new perspectives for development of functional anti-Helicobacter food product(s) for dietary management of H. pylori infection. The essential components of these products could be the most active juices and extracts like quince and cranberry juice supplemented with a corresponding synergist. Further studies are required to investigate the mechanism of antibacterial action of plant products and their efficacy in vivo.