In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran R Phytosome R, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

Obesity-mediated chronic inflammation promotes the progression of obesity to metabolic anti-inflammatory effect of cranberries by decreasing plasma inflammatory cytokines. However, its specific mechanisms of action remain unclear. The nuclear factor-κB (NF-κB) pathway in macrophages plays a critical role in regulating the expression of many inflammatory genes, and histone acetylation has been identified as a key epigenetic modification for the NF-κB p65-mediated inflammatory responses. The objective of the study was to investigate if proanthocyanidin (PAC)-rich cranberry extract (CBE) suppresses histone acetylation and NF-κB p65 activation in RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs). Treatment with 5% and 15% PAC-containing CBEs markedly suppressed the expression of pro-inflammatory mediators (iNos, Cox-2, Tnfα, Mcp-1 and Il-6) in both RAW 264.7 macrophages and BMDMs stimulated with lipopolysaccharides (LPS). CBE significantly reduced LPS-induced phosphorylation of p65 in both cell types without changing total p65 expression levels. Moreover, 15% PAC-CBE increased the expression levels of histone deacetylase 3 (HDAC3) with a concomitant decrease in histone H4 acetylation levels. These results suggest that CBE increases HDAC3 protein expression with the subsequent inhibition of p65 phosphorylation to mediate anti-inflammatory effects in macrophages. Cranberries may serve as a dietary agent to attenuate chronic inflammation in patients with obesity and related complications.

Objectives: We sought to determine whether cranberry juice consumption would ameliorate laboratory and clinical measurements of disease activity in people with rheumatoid arthritis receiving fish oil supplementation.Methods: A prospective study was performed with 62 people with rheumatoid arthritis. We analyzed C-reactive protein modification of the Disease Activity Score-28 (DAS28-CRP) and inflammatory markers. The first group was assigned to eat their typical diet, a second group was asked to consume 3 g of fish oil -3 fatty acids daily, and a third group received both 3 g of fish oil n-3 fatty acids and 500 mL of reduced-calorie cranberry juice daily.Results: Compared with baseline values, the group receiving both fish oil and cranberry juice showed reductions in erythrocyte sedimentation rate (P = 0.033), C-reactive protein (P = 0.002), DAS28-CRP (P = 0.001), adiponectin (P = 0.021), and interleukin-6 levels (P = 0.045), whereas the fish oil group showed decreased DAS28-CRP (P = 0.0261) and adiponectin (P = 0.0239). Differences across treatments showed that the group receiving both fish oil and cranberry experienced reductions (P < 0.05) in erythrocyte sedimentation rate and C-reactive protein compared to the control group and the group treated with fish oil alone, and a reduction in DAS28-CRP was verified when the fish oil and cranberry group was compared to the control group.Conclusions: The ingestion of cranberry juice adds beneficial effects to fish oil supplementation, decreasing disease activity and inflammatory biomarkers in people with rheumatoid arthritis.

Berries are acknowledged as a rich source of major dietary antioxidants and the fact that berry phenolics exhibit antioxidant property is widely accepted. Berries are abundant in Vitamin C and polyphenols such as anthocyanins, flavonoids, and phenolic acids. Polyphenols are found to have several therapeutic effects such as anti-inflammatory, antioxidant, and antimicrobial properties. Increasing studies are focusing on natural products and their components for alternative therapeutics against viral infections. In particular, berries such as elderberry, blueberry, raspberry, and cranberry have proven to be effective against viral infections. Of note, the decoction of Honeysuckle (Lonicera japonica) has been shown to treat viral epidemic diseases. Owing to the rich source of various antiviral constituents, berries could be an alternative source for managing viral infections. In this review, we provide insights into how berry derived components inhibit viral infection and their clinical usefulness in viral disease management.

Cranberry is a dietary supplement popularly used for the prophylaxis of urinary tract infection. Interestingly, cranberry-warfarin interactions in clinical reports have shown bidirectional outcomes. (+or-) Warfarin, a widely prescribed anticoagulant, but with a narrow therapeutic index, contains equal amounts of S- and R-warfarin, of which S-warfarin is more active. The aim of this study was to investigate the effects of different ingestion times of cranberry on the pharmacokinetics and pharmacodynamics of warfarin. Rats were orally administered (+or-) warfarin (0.2 mg/kg) with and without cranberry (5.0 g/kg) at 0.5 h prior to the warfarin, and at 10 h after the warfarin. The plasma concentrations of S- and R-warfarin were determined by LC/MS. The results indicate that cranberry ingested at 0.5 h before (+or-) warfarin significantly decreased the systemic exposures of S-warfarin and R-warfarin. Conversely, when cranberry was ingested at 10 h after (+or-) warfarin, the elimination of S-warfarin was significantly inhibited, and the anticoagulation effect of (+or-) warfarin was significantly enhanced. The results of the mechanism studies indicate that cranberry activated the breast cancer resistance protein (BCRP), which mediated the efflux transports of S-warfarin and R-warfarin. Moreover, the metabolites of cranberry inhibited cytochrome P450 (CYP) 2C9, the main metabolizing enzyme for S-warfarin. In conclusion, cranberry affected the pharmacokinetics of (+or-) warfarin in a bidirectional manner by activating the BCRP by CJ during absorption and inhibiting the BCRP and CYP2C9 by CMs during elimination, depending on the ingestion time of CJ. The combined use of cranberry with warfarin should be avoided.

Purpose: Blueberry and cranberry are rich in anthocyanins. The present study was to investigate the effects of anthocyanin extracts from blueberry and cranberry on body weight and gut microbiota.Methods: C57BL/6 J Mice were divided into six groups (n = 9 each) fed one of six diets namely low-fat diet (LFD), high-fat diet (HFD), HFD with the addition of 1% blueberry extract (BL), 2% blueberry extract (BH), 1% cranberry extract (CL), and 2% cranberry extract (CH), respectively.Results: Feeding BL and BH diets significantly decreased body weight gain by 20-23%, total adipose tissue weight by 18-20%, and total liver lipids by 16-18% compared with feeding HFD. Feeding CH diet but not CL diet reduced the body weight by 27%, accompanied by a significant reduction of total plasma cholesterol by 25% and tumor necrosis factor alpha (TNF-a) by 38%. The metagenomic analysis showed that the supplementation of blueberry and cranberry anthocyanin extracts reduced plasma lipopolysaccharide concentration, accompanied by a reduction in the relative abundance of Rikenella and Rikenellaceae. Dietary supplementation of berry anthocyanin extracts promoted the growth of Lachnoclostridium, Roseburia, and Clostridium_innocuum_group in genus level, leading to a greater production of fecal short-chain fatty acids (SCFA).Conclusions: It was concluded that both berry anthocyanins could manage the body weight and favorably modulate the gut microbiota at least in mice..

The high polyphenols content of cranberry accounts for its strong antioxidant activity underlying the beneficial health effects of this fruit. Rotenone (ROT) is a specific inhibitor of mitochondrial complex I in the brain which leads to the generation of oxidative stress. To date, there are few data indicating that toxicity of ROT is not limited to the brain but can also affect other tissues. We aimed to examine whether ROT-induced oxidative stress could be counteracted by cranberry juice not only in the brain but also in the liver and kidney. Wistar rats were given the combined treatment with ROT and cranberry juice (CJ) for 35 days. Parameters of antioxidant status were determined in the organs. ROT enhanced lipid peroxidation solely in the brain. The increase in the DNA damage was noticed in all organs examined and in leukocytes. The beneficial effect of CJ on these parameters appeared only in the brain. Additionally, CJ decreased the activity of serum hepatic enzymes. The effect of CJ on antioxidant enzymes was not consistent, however, in some organs, CJ reversed changes evoked by ROT. Summing up, ROT can cause oxidative damage not only in the brain but also in other organs. CJ demonstrated a protective effect against ROT-induced toxicity

Candida spp. are pathobionts, as they can switch from commensals to pathogens, responsible for a variety of pathological processes. Adhesion to surfaces, morphological switch and biofilm-forming ability are the recognized virulence factors promoting yeast virulence. Sessile lifestyle also favors fungal persistence and antifungal tolerance. In this study, we investigated, in vitro, the efficacy of two urinary cranberry metabolites, 5-(3',4'-dihydroxy phenyl)-P-valerolactone (VAL) and 4-hydroxybenzoic acid (4-HBA), in inhibiting C. albicans adhesion and biofilm formation. Both the reference strain SC5314 and clinical isolates were used. We evaluated biomass reduction, by confocal microscopy and crystal violet assay, and the possible mechanisms mediating their inhibitory effects. Both VAL and 4-HBA were able to interfere with the yeast adhesion, by modulating the expression of key genes, HWP1 and ALS3. A significant dose-dependent reduction in biofilm biomass and metabolic activity was also recorded. Our data showed that the two cranberry metabolites VAL and 4-HBA could pave the way for drug development, for targeting the very early phases of biofilm formation and for preventing genitourinary Candida infections.

In this paper, an A-type procyanidin (PAC)-rich cranberry extract (CB-B) was obtained mixing different extracts and was formulated with D-mannose and ascorbic acid to obtain a novel nutraceutical (URO-F) aimed at preventing non-complicated bacterial urinary tract infections (UTIs). To assess the bioactivity of CB-B and URO-F, urine samples collected from six healthy volunteers undergoing a 2-days oral consumption of 0.41 g/day of CB-B or 10 g/day of URO-F (corresponding to 72 mg/day of PACs) were tested against uropathogenic E. coli (UPEC) incubated on urinary bladder epithelial cells (T24). Urinary markers of CB-B and URO-F consumption were assessed in the same urine output by UPLC-QTOF-based untargeted metabolomics approach. CB-B and URO-F were evaluated for their ability to promote the intestinal barrier function by restoring the trans-epithelial electrical resistance (TEER) and to inhibit the production of inflammatory cytokines in intestinal epithelial Caco2 cells. CB-B was characterized by a high PAC-A content (70% of total PACs) and a broad distribution of different PACs polymers (dimers-hexamers). Urine from subjects consuming CB-B and URO-F showed a significant effect in reducing the adhesion of UPEC to urothelium in vitro, supporting their efficacy as anti-adhesive agents after oral intake. CB-B inhibited the release of cytokine IL-8, and both products were effective in restoring the TEER. Overall, our results show that the beneficial effects of CB-B and URO-F on UTIs are not only due to the antiadhesive activity of cranberry on UPEC in the urothelium, but also to a multi-target activity involving anti-inflammatory and permeability-enhancing effects on intestinal epithelium.

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P < 0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.