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Long-term effects of three commercial cranberry products on the antioxidative status in rats: a pilot study.

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Authors
Palikova I, Vostalova J, Zdarilova A, Svobodova A, Kosina P, Vecera R, Stejskal D, Proskova J, Hrbac J, Bednar P, Maier V, Cernochova D, Simanek V, Ulrichova J.
Journal
J Agric Food Chem 8(3):1672-8
Abstract

Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.

Recurrent urinary tract infections in older people: the role of cranberry products

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Authors
Sumukadas D, Davey P and McMurdo ME
Journal
Age Ageing 38(3):255-7
Abstract

No abstract - Introduction: Urinary tract infections (UTI) are the commonest bacterial infection in older people. Half of all women experience at least one UTI and the risk increases with age. The present management of recurrent urinary tract infection is prophylaxis with low-dose, long-term antibiotics. However, there is a growing reluctance to prescribe antibiotics unless absolutely essential because of fears about antimicrobial resistance. So the recent resurgence in interest in the potential role of cranberry
products is timely.

The antifungal activity of urine after ingestion of cranberry products.

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Authors
Lee YL, Owens J, Thrupp L, Barron S, Shanbrom E, Cesario T, Najm WI
Journal
J Altern Complement Med 15(9):957-8
Abstract

No abstract - Introduction: Cranberry (Vacinicum macrocarpon) is traditionally used in folk medicine for treatment of urinary tract infections. In a recent study, we established that in addition to the antiadhesion effects, concentrated cranberry juice had a direct antimicrobial effect in vitro. We were also able to confirm a direct antimicrobial activity in vitro against a strain of Klebsiella
pneumoniae, in the urine of subjects after ingestion of a commercial cranberry product. While bacteria are the most common cause of urinary tract infections, frequent or prolonged antimicrobial therapy, use of catheters, severely ill patients, high plasma glucose, and invasive procedures can often lead to candiduria. A review of the literature identified one study (Swartz and Medrek 1968), which reported that cranberry juice (40%) in Sabouraud’s dextrose agar had minimal effect on the growth of Candida albicans compared to 0.087% benzoic acid. In this study, we evaluate the anti-Candida activity of urine specimens after ingestion of cranberry.

A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli.

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Authors
Foo LY, Lu Y, Howell AB, Vorsa N.
Journal
J Nat Prod 63:1225-1228
Abstract

Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4beta-->6)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (4), epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin-(4beta-->8)-epicatechin (5), and epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4beta-->8)-epicatechin (procyanidin B2) (2).

Can a concentrated cranberry extract prevent recurrent urinary tract infections in women? A pilot study.

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Authors
Bailey DT, Dalton C, Joseph Daugherty F, Tempesta MS
Journal
Phytomedicine 14(4):237-41
Abstract

BACKGROUND: Urinary tract infections (UTIs) are extremely prevalent and despite treatment with antibiotics, reoccurrences are common causing frustration in the patient and the potential for developing antibiotic resistance. The use of cranberry products to prevent UTIs has recently become popular and more clinical studies are needed to explore this use.

OBJECTIVE: This open label pilot study examined the ability of a concentrated cranberry preparation to prevent UTIs in women with a history of recurrent infections.

SUBJECTS: Women between the ages of 25 and 70 years old were included with a history of a minimum of 6 UTIs in the proceeding year.

INTERVENTION: The women took one capsule twice daily for 12 weeks containing 200 mg of a concentrated cranberry extract standardized to 30% phenolics.

DESIGN: A questionnaire was used initially to determine the patient's medical history and they were asked at monthly intervals if any of the information had changed. All of the women in the study had urinalysis within 24h before starting on the study preparation and once a month after that for 4 months. Subjects were followed-up approximately 2 years later.

RESULTS: All 12 subjects participated in the 12-week study and were available for follow up 2 years later. During the study none of the women had a UTI. No adverse events were reported. Two years later, eight of the women who continue to take cranberry, continue to be free from UTIs.

CONCLUSION: A cranberry preparation with a high phenolic content may completely prevent UTIs in women who are subject to recurrent infections.

PMID: 17296290 [PubMed - indexed for MEDLINE]

Can cranberry juice be a substitute for cefaclor prophylaxis in children with vesicoureteral reflux?

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Authors
Nishizaki N, Someya T, Hirano D, Fujinaga S, Ohtomo Y, Shimizu T and Kaneko K
Journal
Pediatr Int 51(3):433-4
Abstract

No abstract - Introduction: Urinary tract infection (UTI) is a common childhood infection. In 30–50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), resulting in hospitalizations, and long-term health problems, such as renal scars, hypertension, and end-stage renal disease. To reduce the likelihood of recurrent UTI for children with VUR, antibiotics 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 resistant organisms in the host.

Although cranberry juice prophylaxis was found to reduce the frequency of bacteriuria with pyuria in older women, no studies have yet been reported in the literature on children with VUR. The purpose of this study was to examine whether cranberry juice can be substituted for antibiotic prophylaxis in the prevention of UTI in children with VUR.

Cranberries inhibit LDL oxidation and induce LDL receptor expression in hepatocytes

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Authors
Chu YF, Liu RH
Journal
Life Sci 77(15):1892-901
Abstract

Cardiovascular disease (CVD) is the leading cause of death in most industrialized countries. Cranberries were evaluated for their potential roles in dietary prevention of CVD. Cranberry extracts were found to have potent antioxidant capacity preventing in vitro LDL oxidation with increasing delay and suppression of LDL oxidation in a dose-dependent manner. The antioxidant activity of 100 g cranberries against LDL oxidation was equivalent to 1000 mg vitamin C or 3700 mg vitamin E. Cranberry extracts also significantly induced expression of hepatic LDL receptors and increased intracellular uptake of cholesterol in HepG2 cells in vitro in a dose-dependent manner. This suggests that cranberries could enhance clearance of excessive plasma cholesterol in circulation. We propose that additive or synergistic effects of phytochemicals in cranberries are responsible for the inhibition of LDL oxidation, the induced expression of LDL receptors, and the increased uptake of cholesterol in hepatocytes.

Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects

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Authors
Ushijima K, Tsuruoka S, Tsuda H, Hasegawa G, Obi Y, Kaneda T, Takahashi M
Journal
Br J Clin Pharmacol 68(2):194-200
Abstract

AIM: To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9.

METHODS: The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics.

RESULTS: Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects.

CONCLUSIONS: Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations.

Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin

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Authors
Singh AP, Singh RK, Kim KK, Satyan KS, Nussbaum R, Torres M, Brard L and Vorsa N
Journal
Phytother Res 23(8):1066-74
Abstract

Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells.

Growth inhibitory action of cranberry on Helicobacter pylori.

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Authors
Matsushima M, Suzuki T, Masui A, Kasai K, Kouchi T, Takagi A, Shirai T, Mine T
Journal
J Gastroenterol Hepatol 23(Suppl 2):S175-80
Abstract

BACKGROUND AND AIM: Cranberry is a fruit that originated in North America, and it has been used by Native Americans for bacterial infections. Recent studies have revealed it to be effective for preventing refractory urinary infections, while also suggesting that it plays a possible role in the eradication of Helicobacter pylori (H. pylori).

METHODS: The H. pylori strains used in the present study were NCTC11637 and 11638. Sugar and organic acid-rich, and polyphenol-rich fractions were obtained from cranberry juice concentrate by Amberlite XAD7HP-column chromatography. The H. pylori growth inhibition was estimated by OD(660) and titration in liquid culture, and by an agar dilution plate method. The shapes of the bacteria were analyzed by scanning electron microscopy.

RESULTS: Cranberry extract suppressed bacterial proliferation in a dose-dependent manner. In the comparison with other juices, polyphenol-rich fruits (cranberries, blueberries, and red grapes) showed similar growth inhibitory activity, whereas polyphenol-poor fruits (oranges, pineapples, apples, and white grapes) did not show any activity. The polyphenol-rich fraction of cranberry maintained the H. pylori-growth inhibitory activity. More bacteria in a coccoid form were observed after culture with cranberry.

CONCLUSION: Cranberry extract inhibited H. pylori proliferation and it is suggested that polyphenols are responsible for this action. The morphological analysis suggested that cranberry induces H. pylori to develop a coccoid form, thereby inhibiting its growth bacteriostatically. Further basic studies to clarify these mechanisms in combination with in vivo studies are needed.