Background: Urinary tract infection (UTI) is a renal infection that affects the urinary tract and is global problem related to health and many people are affected each year at some points of their lives. Modern studies about urinary tract infections show that almost one third of the world's population has been suffering from this ailment. Different antibacterial medicines have been reported to have resistance against pathogens. In order to overcome the problem, exploration for new and dynamic antibacterial agents from natural sources is the emerging trend. 

Primary study objective: The primary objective was to evaluate the efficacy and safety of the polyherbal test drug formulation, "Crano-cure", as treatment for UTIs. 

Methods/design: In the current study, clinical trials were designed to evaluate the effects of the polyherbal formulation "Crano-cure" compared to the standard drug Ciprofloxacin in randomized, controlled multicenter trial of 205 patients, analyzing clinical outcomes and safety profiles. 

Setting and participants: Conducted across multiple centers, including Shifa-ul-Mulk Memorial Hospital at Hamdard University Karachi and three other clinics, the study involved 205 patients aged 15-60, irrespective of their socioeconomic status. 

Intervention: Patients were classified into two groups i.e. control group (ciprofloxacin) and the test group (crane-cure). Polyherbal formulation of 500 mg Crano-cure capsules two times in a day were administered to the test group for 28 days. The control group was administered a control ciprofloxacin tablet 500 mg two times in a day for 28 days. 

Primary outcome measures: The drug was found safe for further clinical study after observing changes or improvements in UTI symptoms, urine culture and blood complete tests. The clinical trial was dully registered on the US National Library of Medicine, ClinicalTrials.gov Identifier: NCT04575493. The trial was accompanied in the instructions of EC (Ethical Committee). The study plan and procedures were displayed to the BASR (Board of Advance Studies and Research) and board members of the Ethical Committee (EC), which was ERB-2021-9-1. 

Results: Clinical study results revealed the effectiveness of Crano-cure in the management of UTIs symptoms and hematological and biochemical parameters including blood complete test, liver function tests, renal function tests and lipid profile. Moreover, the test drug Crano-cure revealed a significance level (P ≤ .05) in compliance and cost-effectiveness compared to control ciprofloxacin.

Background: Improving the efficiency of treatment and prevention of recurrent lower urinary tract infection (LUTI) is an important problem in modern urology. A significant role is given to the non-antibiotic measures. 

Aim: To evaluate the clinical and microbiological efficiency of the drug Urolife-Next in patients with recurrent UTI. 

Materials and methods: A total of 70 women with recurrent UTI aged 18 to 55 years (mean 35.1+/-10.1) and symptoms of cystitis were included in the study. After antibacterial therapy, all patients were divided into 3 groups. In the group 1 (n=24), patients took Urolife-Next 1 capsule 3 times a day for 90 days, in the group 2 (n=23) Urolife-Next in the same dose, but for a period of 30 days, while patients of group 3 (n=23) did not receive any treatment. The total follow-up period was 90 days. Frequency and severity of symptoms of recurrent UTI were assessed. The microbiological part of the study included evaluation of the presence and severity of anti-adhesive, anti-biofilm and direct antibacterial effects of the Urolife-Next against uropathogens isolated from urine of patients with exacerbation of UTI. 

Results: In group 1, in which patients took Urolife-Next throughout the study, the lowest frequency of relapses was seen. During the 90-day follow-up, recurrences of UTI occurred in only 3 (12.5%) patients in group 1, compared to 18 (78.3%) in group 3. In addition, in the group 1 there was a significantly lower severity of symptoms during exacerbation of cystitis compared to the initial episode, as well as to 3. Urolife-Next showed antibacterial activity against 29 (41.4%) of 70 strains of uropathogens. The minimum inhibitory concentration of Urolife-Next against gram-negative microorganisms was on average 2 times higher than for gram-positive pathogens. A pronounced anti-adhesive activity of Urolife-Next in vitro was also revealed. The maximum anti-adhesive effect was observed 2 hours after the start of the study. By this time, the adhesion index for cultures in the presence of Urolife-Next was 2.3 times lower than the control values for E. coli, 2.5 times for Kl. pneumoniae, and 2.9 times for E. faecalis. Significant antibiofilm activity of Urolife-Next was also noted. The severity of biofilm formation, which was assessed by changes in the optical density of cultures, decreased by 1.3-2.2 times, depending on the type of uropathogens. 

Conclusions: The results of the study prove the efficiency of the dietary supplement Urolife-Next for the prevention of recurrences in patients with UTI. Its components (D-mannose, cranberry extract, vitamins D and C, hyaluronic acid, probiotics) influence the main pathogenetic factors.

While many beneficial host-microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn's disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type M (CTM) on adherent-invasive Escherichia coli (AIEC) LF82, a pathobiont associated with CD. Different stages of pathogenic infection were investigated: (i) colonization of the mucus layer, and (ii) adhesion to and (iii) invasion of the epithelial cells. Following 48 h of fecal batch incubation, 0.5 and 1 mM of CTM significantly altered AIEC LF82 levels in a simulated mucus layer, resulting in a decrease of 50.5% in the untreated blank, down to 43.0% and 11.4%, respectively. At 1 mM of CTM, the significant decrease in the levels of AIEC LF82 coincided with a stimulation of the metabolic activity of the background microbiota. The increased levels of health-associated acetate (+7.9 mM) and propionate levels (+3.5 mM) suggested selective utilization of CTM by host microorganisms. Furthermore, 1 mM of both fermented and unfermented CTM decreased the adhesion and invasion of human-derived epithelial Caco-2 cells by AIEC LF82. Altogether, this exploratory in vitro study demonstrates the prebiotic potential of CTM and supports its antipathogenic effects through direct and/or indirect modulation of the gut microbiome.

OBJECTIVE: Despite conflicting evidence, it is common practice to use continuous antibiotic prophylaxis (CAP) in patients with indwelling double-J (DJ) stents. Cranberry extracts and d-mannose have been shown to prevent colonization of the urinary tract. We evaluated their role in this setting.METHODS: We conducted a prospective randomized study to evaluate patients with indwelling DJ stents following urological procedures. They were randomized into three groups. Group A (n=46) received CAP (nitrofurantoin 100 mg once daily [OD]). Group B (n=48) received cranberry extract 300 mg and d-mannose 600 mg twice daily (BD). Group C (n=40) received no prophylaxis. The stents were removed between 15 days and 45 days after surgery. Three groups were compared in terms of colonization of stent and urine, stent related symptoms and febrile urinary tract infections (UTIs) during the period of indwelling stent and until 1 week after removal.RESULTS: In Group A, 9 (19.5%) patients had significant bacterial growth on the stents. This was 8 (16.7%) in the Group B and 5 (12.5%) in Group C (p-value: 0.743). However, the culture positivity rate of urine specimens showed a significant difference (p-value: 0.023) with Group B showing least colonization of urine compared to groups A and C. There was no statistically significant difference in the frequency of stent related symptoms (p-value: 0.242) or febrile UTIs (p-value: 0.399) among the groups.CONCLUSION: Prophylactic agents have no role in altering bacterial growth on temporary indwelling DJ stent, stent related symptoms or febrile UTIs. Cranberry extract may reduce the colonization of urinary tract, but its clinical significance needs further evaluation.

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..