Organic anion-transporting polypeptide (OATP) 1A2 and OATP2B1 mediate the intestinal absorption of drugs. This study aimed to identify fruit juices or fruit juice components that inhibit OATPs and assess the risk of associated food-drug interactions. Inhibitory potency was assessed by examining the uptake of [H-3]estrone 3-sulfate and [H-3]fexofenadine into HEK293 cells expressing OATP1A2 or OATP2B1. In vivo experiments were conducted using mice to evaluate the effects of cranberry juice on the pharmacokinetics of orally administered fexofenadine. Of eight examined fruit juices, cranberry juice inhibited the functions of both OATPs most potently. Avicularin, a component of cranberry juice, was identified as a novel OATP inhibitor. It exhibited IC50 values of 9.0 and 37 mu M for the inhibition of estrone 3-sulfate uptake mediated by OATP1A2 and OATP2B1, respectively. A pharmacokinetic experiment revealed that fexofenadine exposure was significantly reduced (by 50%) by cranberry juice. Cranberry juice may cause drug interactions with OATP substrates.

Background: Type 2 diabetes (T2D) is a polygenic metabolic disease, characterized by high fasting blood glucose (FBG). The ability of cranberry (CRN) fruit to regulate glycemia in T2D patients is well known. Here, a cohort of 13 lines of the genetically diverse Collaborative Cross (CC) mouse model was assessed for the effect of non- dialyzable material (NDM) of cranberry extract in lowering fasting blood glucose. Methods: Eight-week-old mice were maintained on either a standard chow diet (control group) or a high-fat diet (HFD) for 12 weeks, followed by injections of intraperitoneal (IP) NDM (50 mg/kg) per mouse, three times a week for the next 6 weeks. Absolute FBG (mg/dl) was measured bi-weekly and percentage changes in FBG (%FBG) between weeks 0 and 12 were calculated. Results: Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD. However, a non-significant in-crease in FBG values was observed in male and female mice maintained on HFD during the same period. Following administration of NDM during the following 6 weeks, the results show a variation in significant levels of FBG lowering between lines, male and female mice and under the different diets. Conclusion: The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background (pharmacogenetics), sex of the mouse (pharmacosex), and diet (pharmacodiet). All these results support the need for follow-up research to better understand and implement a personalized medicine approach/utilization of NDM for reducing FBG.

Importance There is little consensus on an effective nonantibiotic agent for the prevention of urinary tract infection (UTI) after pelvic reconstructive surgery. Objective The aim of the study was to investigate the impact of methenamine hippurate with cranberry capsules on rates of UTI after pelvic reconstructive surgery, among patients requiring short-term catheterization. Study Design In this randomized, double-blinded placebo-controlled trial, patients discharged with a catheter after pelvic reconstructive surgery were approached to participate. Participants were randomized to receive cranberry with methenamine or cranberry with placebo. Primary outcome was number of UTIs treated within 1 week after surgery. Secondary outcomes included incidence of UTIs treated within 6 weeks postoperatively, bacterial species on culture, urinary pH, catheter duration, patient adherence, and satisfaction. A sample size of 88 participants per arm was planned. Results From June 2019 to July 2021, 185 patients were randomized and 182 analyzed; 89 received placebo and 93 received methenamine. Both groups were similar. Incidence of UTI at 1 week was significantly higher in the placebo group (79.8%) compared with the methenamine group (66.7%; odds ratio, 1.97; 95% confidence interval, 1.01-3.87; P = 0.048). This difference increased by 6 weeks postoperatively (89.9% vs 72.0%; odds ratio, 3.45; 95% confidence interval, 1.51-7.87; P = 0.003). There were fewer pseudomonal UTIs in the methenamine group (P = 0.041). Duration of catheterization and urinary pH were similar. Overall adherence and level of satisfaction was high. Conclusions In this high-risk population, methenamine was well tolerated and significantly reduced UTI rates. Methenamine with cranberry should be considered as an effective prophylactic therapy to reduce this common complication after pelvic surgery.

Rich in polyphenols, cranberry juice (CJ) with high antioxidant activity is believed to contribute to various health benefits. However, our knowledge of the neuroprotective potential of cranberries is limited. Previously, we have demonstrated that CJ treatment controls oxidative stress in several organs, with the most evident effect in the brain. In this study, we examined the capability of CJ for protection against Parkinson's disease (PD) in a rotenone (ROT) rat model. Wistar rats were administered with CJ in a dose of 500 mg/kg b.w./day (i.g.) and subcutaneously injected with ROT (1.3 mg/kg b.w./day). The experiment lasted 45 days, including 10 days pretreatment with CJ and 35 days combined treatment with CJ and ROT. We quantified the expression of alpha-synuclein and apoptosis markers in the midbrain, performed microscopic examination, and assessed postural instability to evaluate the CJ neuroprotective effect. Our results indicate that the juice treatment provided neuroprotection, as evidenced by declined alpha-synuclein accumulation, Bax and cleaved/active caspase-9 expression, and normalized cytochrome c level that was accompanied by the enhancement of neuronal activity survival and improved postural instability. Importantly, we also found that long-term administration of CJ alone in a relatively high dose may exert a deleterious effect on cell survival in the midbrain.

The oral cavity harbors hundreds of microorganisms that may be uncontrolled and provoke several diseases. In this sense, periodontitis is a complex multifactorial disease with an essential microbial component in its etiology. Periodontal treatment involves mechanical control of the supra- and subgingival biofilm, but not all patients respond predictably to treatment. In this way, the biofilm chemical control helps in the reduction of periodontal pathogens during treatment or in the delay of bacterial re-colonization after scaling and root planning. Several products have been studied as adjunctive therapy and have shown promising results. Therefore, the present article reviews the biological effects of propolis, aloe vera, green tea, cranberry, calendula, myrrha and salvia that may support their use in the control of subgingival biofilm in patients with periodontitis. All the natural products cited above showed exciting results against microorganisms related to oral diseases, mainly periodontitis. These substances also have anti-inflammatory and antioxidant activities. The natural agents propolis, aloe vera, green tea, cranberry, calendula, myrrha and salvia demonstrated potential to be used as oral hygiene products, based on their antimicrobial and anti-inflammatory actions.

High sugar intake has been associated with adverse effects on health, with some types of breakfast being highly linked to overweight and obesity. The aim was to compare the effects of four sugar-free breakfast items, apricot jam with white bread (JWB), white bread (WB), cocoa with fat-free milk (CM), and dried cranberry cereal bar (CB), compared to d-glucose on the glycaemic responses. Using a cross-over design, twelve healthy individuals (25 +/- 4 years; BMI 22 +/- 2 kg/m(2)) received isoglucidic test meals (25 g of available carbohydrate) and 25 g glucose reference, in random order. Glycaemic index/load (GI/GL) were calculated, and capillary blood glucose samples were collected at 0-120 min after meal consumption. Subjective appetite was assessed with visual analogue scales. Sugar-free apricot jam and cocoa powder contained traces of available carbohydrates and were consumed along with bread and fat-free milk, respectively. JWB and WB were classified as medium GI, low-to-medium GL; CM as medium GI, low GL; and CB as high GI, low-to-medium GL. Subjective hunger was lower after JWB, fullness was higher after CM and pleasure was higher after CB (P for all < 0.05). In conclusion, sugar-free apricot jam with and without WB and cocoa powder with fat-free milk are suitable healthy breakfast options leading to improved glycaemic and subjective appetite responses.

The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness.

Helicobacter pylori infection is one of the most common chronic bacterial infections. Cranberry has been suggested for H. pylori eradication. We aimed to conduct the first meta-analysis to summarise current evidence on effects of cranberry supplementation on H. pylori eradication in H. pylori positive subjects. We searched the online databases up to December 2020. Four randomised clinical trials (RCT) were included with human subjects, investigating the effect of cranberry on H. pylori eradication. The pooled results were expressed as the OR with 95% CI. Based on five effect sizes with a total sample size of 1935 individuals, we found that according to the OR, there was a positive effect of cranberry supplementation on H. pylori eradication, increasing the chance of H. pylori eradication by 1.27 times, but this relationship was not statistically significant (overall OR: 1.27; 95% CI 0.63, 2.58). The results also indicated the moderate between-study heterogeneity (I2 = 63.40%; P = 0.03) of the studies. However, there were no significant differences in some subgroup analyses in the duration of treatment, the duration of follow-up and the Jadad score. Our findings revealed that although cranberry had a positive effect on H. pylori eradication in adults, this effect was not statistically significant. Due to the small number of included studies and moderate heterogeneities, the potential of cranberry supplementation on H. pylori eradication should be validated in large, multicentre and well-designed RCT in the future.

Oxidative stress is a key underlying factor in cognitive decline and atherosclerosis. Oxidative stress occurs at the cellular level with an imbalance between reactive oxygen species and reactive nitrogen species and a deficiency in antioxidants. Mounting evidence suggests that berry flavonoids may promote cellular health by exerting antioxidant properties. Black currant and various berry extracts were tested in microglia (BV-2) and cardiomyocyte (HL-1) cell lines to study their biological effects. The principal ingredients in black currant and cranberry extract-delphinidin 3-rutinoside (D3R) and cyanidin 3-glucoside (C3G), were also assessed. A menadione-induced oxidative stressor was used, and its output was quantified to detect oxidative stress (CellROX (TM)). Black currant extract had similar antioxidant effects as N-acetylcysteine (NAC) in HL-1 cells with regard to cellular protection, whereas cranberry extract was ineffective. In contrast, cranberry extract was comparable in effectiveness to black currant extract in BV-2 cells. D3R and C3G also reduced oxidative stress similarly to whole berry extracts, which indicates that these ingredients may confer the antioxidant effects of berries. Black currant and cranberry extracts inhibit oxidative stress in microglial and cardiomyocyte cell lines. Black currant extract was more effective in reducing oxidative stress in the HL-1 cells, whereas cranberry extract was comparable in reducing oxidative stress in the BV-2 cells. The results suggest that berry flavonoids exert neuro- and cardioprotective effects.

Objective: To provide a critical analysis of evidence describing the implementation and effectiveness of cranberry products for the prevention of urinary tract infections in the setting of residential aged care. Methods: A critical analysis of the literature. Results: The current evidence indicates that cranberry products decrease the occurrence of urinary tract infections in aged care residents who are likely to benefit from the use of cranberry products as a preventative measure; however, some of the results were limited and contradictory, because of gaps and insufficient research in relation to the active ingredients of cranberries - proanthocyanins. Conclusion: This critical analysis demonstrates benefits in the use of cranberry products in the prevention of urinary tract infections for residents of aged care facilities. Further research and education on preventative measures could potentially lower the use of antibiotics and the incidence of urinary tract infections in residential aged care.