The treatment of chronic pelvic pain syndrome (CPPS) is based on antibiotic therapy, but many patients experience a relapse after treatment. Cranberry juice is known for its roles in both the treatment and prevention of urinary tract infections. This study was performed to evaluate the effectiveness of cranberry juice in the prevention of a relapse after the treatment of CPPS.
Materials and Methods: Fifty patients, diagnosed as CPPS (National Institutes of Health; NIH-catagory IIIa), were included in this study. All the patients had initially been treated with levofloxacin and supportive treatment for 8-12 weeks. After completion of the initial treatment, 26 olunteer patients were recommended to drink 150ml of cranberry juice twice a day, 24 patients, as a control group, received no cranberry juice and all the patients re-evaluated after 3 months. Results: On initial diagnosis, the white blood cell (WBC) count in the high power field (HFP) of expressed prostatic secretions (EPS) and the NIHChronic
Prostatitis Symptom Index (NIH-CPSI) in cranberry group were 18.2±3.4 and 23.1±4.4 and those of the control group 16.4±4.8 and 22.4±3.7, respectively. When the medical treatment was ended, the WBC of the EPS and NIH-CPSI in the cranberry group were 2.5±2.1 and 14.1±4.1, and those of the control group were 2.7±1.9 and 13.7±2.1, respectively. After the three month follow-up, the cranberry group showed a WBC of 2.2±2.5 in the EPS and a NIH-CPSI of 12.7±3.9, a slight decrease or similar result compared to the treatment completion period. No patient showed aggravation of symptoms after drinking cranberry juice, whereas five from the control group did. Conclusions: Cranberry juice showed an effect in the prevention of a relapse in CPPS patients, with no adverse effects.

Flavonoid-rich diets are associated with a lower mortality from cardiovascular disease. This has been linked to improvements in endothelial function. However, the specific flavonoids, or biologically active metabolites, conferring these beneficial effects have yet to be fully defined. In this experimental study of the effect of flavonoids on endothelial function cultured endothelial cells have been used as a bioassay with endothelin-1 (ET-1) synthesis being measured an index of the response.
Evaluation of the relative effects of extracts of cranberry juice compared to apple, cocoa, red wine, and green tea showed inhibition of ET-1 synthesis was dependent primarily on their oligomeric procyanidin content. Procyanidin-rich extracts of cranberry juice triggered morphological changes in endothelial cells with reorganization of the actin cytoskeleton and increased immunostaining for phosphotyrosine residues. These actions were independent of antioxidant activity. Comparison of the effects of apple procyanidin monomers through heptamer showed a clear structure-activity
relationship. Although monomer, dimer, and trimer had little effect on ET-1 synthesis, procyanidin tetramer, pentamer, hexamer, and heptamer produced concentration-dependent decreases with IC50 values of 5.4, 1.6, 0.9, and 0.7 μM, respectively. Levels of ET-1 mRNA showed a similar
pattern of decreases, which were inversely correlated with increased expression of Kruppel-like factor 2 (KLF2), a key endothelial transcription factor with a broad range of antiatherosclerotic actions including suppression of ET-1 synthesis. Future investigations of procyanidin-rich products should assess the role KLF2 induction plays in the beneficial vascular effects of high flavonoid consumption.

The present study investigated the effect of cranberries on development of colon tumors induced by azoxymethane in Fisher 344 male rats. Fifty five rats were divided into five groups and fed with control (AIN 93) or treatment diets: cranberry meal (5, 10%) cranberry juice (2.5, 5%). Two AOM (16 mg kg-1 b.wt.) injections were given weekly for 2 weeks for induction of colon tumors. At 45 weeks of age, all rats were killed and colons were evaluated for tumor incidence, size of tumor and tumor multiplicity. Selected hepatic phase 1 (CYP2E1), phase 11 (GST) and antioxidative enzyme (catalase and SOD) activities were determined. Tumor size and tumors/tumor bearing rat were higher (p<=0.05) in the control group. Number of tumors was lower in cranberry fed rats compared to control. Administration of cranberry to rats increased (p<0.05) hepatic enzyme activities by 1.2-3.7 fold compared to control fed rats. These results indicate that feeding cranberry (meal and juice) inhibited colon tumors induced by AOM and enhanced the activity of hepatic enzymes.

Abstract. Background: Traditional Botanical Supplement-
101 (TBS-101) is a newly developed proprietary botanical
agent containing seven standardized botanical extracts,
including: Panax ginseng, cranberry, green tea, grape skin,
grape seed, Ganoderma lucidum and chamomile. Each of the components has been consumed either in the regular diet or as natural supplement. When used as a single agent, each of these seven botanicals has been implicated in
chemoprevention and therapy in various types of cancer. The anticancer effect of TBS-101, with the specific combination of these anti-cancer botanicals for the treatment of prostate cancer (PCa), has not been tested. Materials and Methods: The IC50 and the effect of TBS-101 on the proliferation and apoptosis of PC-3 cells were determined. Tumor xenograft mice were generated by subcutaneously implanting PC-3 cells into mice and tumors were allowed to grow to different sizes before starting the treatment. The effects of TBS-101 on tumor growth were assessed by measuring tumor size and by histological, pathological and immunohistochemical analyses. A basic toxicity study was performed to test the tolerance of the mice to high doses of TBS-101. Results: Treatment of the PC-3 cells with TBS-101 resulted in a dosedependent
inhibition of cell growth, with an IC50 of 1.4 μg/ml. A concomitant induction of apoptosis in PC-3 cells
treated with TBS-101 was also observed. Upon the treatment with TBS-101, all three groups of mice bearing moderate or large tumors showed significant inhibition of tumor growth and invasion. In contrast, control mice treated with vehicle alone had significant tumor growth and lymph node metastasis. In the basic toxicity studies, high doses of TBS- 101 exerted no toxicity in healthy or tumor-bearing mice. Conclusion: The natural botanical agent TBS-101 has a good safety profile and significant anticancer activities in hormone-refractory PC-3 cells and large aggressive PC-3 tumors in a xenograft mouse model and has great potential for the treatment of aggressive prostate cancer

The potential risk of herb drug interactions is of particular focus today owing to the increasing and inadvertent use of herbs in recent times. It is a major safety concern for the drugs with narrow therapeutic index like warfarin, a most common anticoagulant with the maximum number of interactions reported. The objective of the present study was to conduct a systemic review of literature to consolidate the clinical case reports of warfarin–herb interactions and to assess the report reliabilities. We reviewed the published clinical literature to consolidate and
assess the interactions between various herbs and warfarin, based on reported adverse events, descriptions of the clinical case reports and case series using electronic databases as well as hand picked references from the year 1971 to year 2007 and ranked them on likely causality
using Naranjo’s algorithm. Out of 72 cases of documented case reports of warfarin with various herbs, 84.7% cases were evaluated as possible interactions (61/72) and 15.3% cases (11/72) as probable interactions. Cranberry juice was most commonly involved in interactions with warfarin with 34.7% of cases (25/72) of which 92% cases were possible interactions (23/25) and 8% cases (2/25) were probable
interactions. Hence, we conclude that combining anticoagulant medicines with herbs appears to be a risky proposition. The number of herbs reported to interact with warfarin continues to expand. Patients on warfarin are specifically advised to avoid taking herbal medicines or to
have their INR measured within two weeks of starting the drug, to be on a safer side. Further, more systematic studies pertaining to warfarin herb interactions are urgently warranted.

Ethyl acetate extracts of Sephadex LH20-purified proanthocyanidins of American cranberry (Vaccinium macrocarpon Ait.) exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing a-Gal(1 4 4)b-Gal receptor sequences similar to those on epithelial cells in the urinary tract. The chemical structures of the proanthocyanidins were determined by 13C NMR, electrospray mass spectrometry, matrix-assisted
laser absorption time-of-flight mass spectrometry and by acid catalyzed degradation with phloroglucinol. The proanthocyanidin molecules consisted predominantly of epicatechin units with mainly DP of 4 and 5 containing at least one A-type linkage. The procyanidin A2 was the most common terminating unit occurring about four times as frequently as the epicatechin monomer

In this study, the chemopreventive potential of Cranberry was analyzed in reducing the Aberrant Crypt Foci (ACF) induced by Azoxymethane (AOM) in Fisher 344 male rats. After 1 week period of acclimatization, rats were divided into five different groups. Cranberry meal was mixed in an AIN 93G based diet at 5 and 10% and juice was provided at 2.5 and 5%. Daily feed intake and weekly body weights were recorded. At 17 week of age, rats were killed and samples were collected. Number of ACF and number of crypts/foci were enumerated in the colon. There were no significant differences in feed intake, weight gain, cecal weight and cecal pH among all groups. Total ACF incidence (119) was significantly (p<0.05) higher in control group than in treatment groups. Reduction in total ACF induction was higher in rats fed 10% Cranberry (65.75%) compared to control. A two to six fold increase in selected hepatic enzymes activities (units/mg enzyme) were seen in rats fed 5 and 10% treatment diets compared to control. Results of this study showed that administration of Cranberry meal and juice resulted in significant (p<0.05) reductions in the incidence of ACF in azoxymethane induced preneoplastic lesions.

Cranberry and its products are important components of the cranberry processing industry and have historically been associated with positive health benefits such as preventing urinary tract infections. These health benefits are associated with phenolic phytochemicals in the juice which are now known to have potential for inhibition of development and progression of cancer and cardiovascular diseases. Helicobacter pylori is an important human pathogen linked to peptic ulcer and now to cardiovascular diseases. Control of this pathogen using synthetic antimicrobials such as currently approved antibiotics has limitations due to potential development of resistance and low compliance. We believe a profile of antimicrobials compared to a single compound could be potentially more effective in managing H. pylori infections. We have investigated the effect of cranberry, blueberry and grape seed extracts on inhibiting H. pylori have been investigated. The ability of blueberry, grape seed and oregano extract on enhancing the antioxidant and anti-H. pylori activity of cranberry powder in a mixture was also investigated. The anti-H. pylori activity of the cranberry fruit extracts and their synergies correlated with antioxidant activity and the presence of biphenyls as well as polyphenolic phytochemicals. The anti-H. pylori activity of cranberry juice extract was significantly improved by its synergistic blending with blueberry, grape seed and oregano extract. The lower efficacy of purified phenolics in inhibiting H. pylori compared with fruit powder at similar dosage levels suggests a synergistic mode of functionality of these individual phenolics in whole food background. Consumption of blends of fruit juices with other fruit as well as herb extracts can impart unique functional attributes and could be an effective strategy in developing diet-based management of H. pylori infections as well as other oxidation linked diseases.

Cranberry fruit is a rich source of polyphenols, and has shown biological activities against Streptococcus mutans. In the present study, we examined the influence of extracts of flavonols (FLAV), anthocyanins (A) and proanthocyanidins (PAC) from cranberry on virulence factors involved in Streptococcus mutans biofilm development and acidogenicity. PAC and FLAV, alone or in combination, inhibited the surface-adsorbed glucosyltransferases and F-ATPases activities, and the acid production by S. mutans cells. Furthermore, biofilm development and acidogenicity were significantly affected by topical applications of PAC and FLAV (P0.05). Anthocyanins were devoid of any significant biological effects. The flavonols are comprised of mostly quercetin glycosides, and the PAC are largely A-type oligomers of epicatechin. Our data show that proanthocyanidins and flavonols are the active constituents of cranberry against S. mutans.

Background and purpose: Patients commonly take complementary medicines in conjunction with warfarin yet evidence supporting the safety or the risk of a herb–drug interaction is lacking. The aim of this study was to investigate the possible impact of two commonly used herbal medicines, garlic and cranberry, on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects. Experimental approach: An open-label, three-treatment, randomized crossover clinical trial was undertaken and involved 12 healthy male subjects of known CYP2C9 and VKORC1 genotype. A single dose of 25mg warfarin was administered alone or after 2 weeks of pretreatment with either garlic or cranberry. Warfarin enantiomer concentrations, INR, platelet aggregation and clotting factor activity were measured to assess pharmacokinetic and pharmacodynamic interactions between warfarin and herbal medicines. Key results: Cranberry significantly increased the area under the INR–time curve by 30% when administered with warfarin compared with treatment with warfarin alone. Cranberry did not alter S- or R-warfarin pharmacokinetics or plasma protein binding. Co-administration of garlic did not significantly alter warfarin pharmacokinetics or pharmacodynamics. Both herbal medicines showed some evidence of VKORC1 (not CYP2C9) genotype-dependent interactions with warfarin, which is worthy of further investigation.Conclusions and implications: Cranberry alters the pharmacodynamics of warfarin with the potential to increase its effectssignificantly. Co-administration of warfarin and cranberry requires careful monitoring.