Abstract: BACKGROUND: Bacteria within a biofilm are phenotypically more resistant to antibiotics, desiccation, and the host immune system, making it an important virulence factor for many microbes. Cranberry juice has long been used to prevent
infections of the urinary tract, which are often related to biofilm formation. Recent studies have found that the A-type proanthocyanidins from cranberries have anti-biofilm properties against Escherichia coli.
METHODS: Using crystal violet biofilm staining, resazurin metabolism assays, and confocal imaging, we examined the ability of A-type proanthocyanidins (PACs) to disrupt the biofilm formation of Pseudomonas aeruginosa. We used mass spectrometry to analyze the proteomic effects of PAC treatment. We also performed synergy assays and in vitro and in vivo infections to determine whether PACs, alone and in combination with gentamicin, could contribute to the killing of P. aeruginosa and the survival of cell lines and G. mellonella. RESULTS: Cranberry PACs reduced P. aeruginosa swarming motility. Cranberry PACs significantly disrupted the biofilm formation of P. aeruginosa. Proteomics analysis revealed significantly different proteins expressed following PAC treatment. In addition, we found that PACs potentiated the antibiotic activity of gentamicin in an in vivo model of infection using G. mellonella. CONCLUSIONS: Results suggest that A-type proanthocyanidins may be a useful therapeutic against the biofilm-mediated infections caused by P. aeruginosa and
should be further tested.
Abstract: The use of dietary supplements containing cranberry extract is a common way to prevent urinary tract infections. As consumption of these supplements containing a mixture of concentrated anthocyanins and proanthocyanidins has increased, interest in their possible interactions with drug-metabolizing enzymes has grown. In this in vivo study, rats were treated with a standardized cranberry extract
(CystiCran®) obtained from Vaccinium macrocarpon in two dosage schemes (14 days, 0.5 mg of proanthocyanidins/kg/day; 1 day, 1.5 mg of proanthocyanidins/kg/day). The aim of this study was to evaluate the effect of anthocyanins and proanthocyanidins contained in this extract on the activity and expression of
intestinal and hepatic biotransformation enzymes: cytochrome P450 (CYP1A1, CYP1A2, CYP2B and CYP3A), carbonyl reductase 1 (CBR1), glutathione-S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Administration of cranberry extract led to moderate increases in the activities of hepatic CYP3A (by 34%), CYP1A1 (by 38%), UGT (by 40%), CBR1 (by 17%) and GST (by 13%), while activities of these enzymes in the small intestine were unchanged. No changes in the relative amounts of these proteins were found. Taken together, the interactions of cranberry extract with simultaneously administered drugs seem not to be serious.
Abstract: Little information is available about drug interactions with cranberry juice (CJ). Using microsomes from the human liver and rat small intestine, this study was designed to determine whether CJ could inhibit CYP3A-mediated nifedipine (NFP) oxidase activity; it showed that CJ was a potent inhibitor of human and rat CYP3A. Preincubation with 10% vol/vol of CJ and 1 mM NADPH for 10 min resulted in significant inhibition of the NFP oxidation activity of human and rat CYP3A (18.2 and 12.6% decreases, respectively, compared with preincubation experiments without NADPH). In addition, the pharmacokinetic interaction between CJ and NFP in vivo was confirmed in rats. In comparison with a control group, the area under the concentration-time curve (AUC) of NFP was approximately 1.6-fold higher when CJ (2 mL) was injected intraduodenally 30 min before the intraduodenal administration of NFP (30 mg kg(-1)). However, the mean residence time, the volume of distribution and the elimination rate constant were not changed significantly. These data suggest that CJ component(s) inhibit the function of enteric CYP3A. In conclusion, it was found that CJ inhibits the CYP3A-mediated metabolism of NFP in both rats and humans. Furthermore, CJ alters NFP pharmacokinetics in rats.