Cranberry (Vaccinium macrocarpon) dietary supplementation can help prevention of urinary tract infections through the supply of proanthocyanidin-type polyphenols (PAC). The main uropathogenic bacteria are members of the intestinal microbiota. A randomized cross-over experiment was done to investigate whether cranberry dietary supplementation affects concentrations of thermotolerant coliforms, Enterococcus spp. and Lactobacillus spp. in rat faeces. Thirteen rats, housed in individual cages, received successively two diets as pellets during 7 days each: a standard diet without polyphenols and the standard diet supplemented with cranberry powder containing 10.9 mg/100 g of PAC. There was a 7 days wash-out period in between with standard diet without polyphenols. Body weight and feed intake were recorded. Faeces were collected on the last day of treatment, and crushed to count the different bacterial populations using the most probable number method. Thermotolerant coliforms were grown in BGBLB tubes and on MacConkey agar. Enterococcus spp. were grown in Rothe and Litsky broths and on KF Streptococcus agar. Lactobacillus spp. were grown in Man Rogosa Sharpe broth. Body mass gains were not affected by cranberry supplementation. This is consistent with equal food intake, cranberry powder not providing significant energy supplement. Cranberry dietary supplementation was associated with changes in fecal concentrations of thermotolerant coliforms, and Enterococcus spp. in some rats, but did not induce significant changes in bacterial fecal concentrations in a global population of 13 rats. In conclusion, we did not observe any significant effect of dietary cranberry supplementation on the fecal microbiota of Wistars rats for a 7-day diet.

Hazara virus (HAZV) belongs to the Nairoviridae family and is included in the same serogroup of the Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is the most widespread tick-borne arbovirus. It is responsible for a serious hemorrhagic disease, for which specific and effective treatment and preventive systems are missing. Bioactive compounds derived from several natural products may provide a natural source of broad-spectrum antiviral agents, characterized by good tolerability and minimal side effects. Previous in vitro studies have shown that a cranberry (Vaccinium macrocarpon Ait.) extract containing a high content of A-type proanthocyanidins (PAC-A) inhibits the replication of herpes simplex and influenza viruses by hampering their attachment to target cells. Given the broad-spectrum antimicrobial activity of polyphenols and the urgency to develop therapies for the treatment of CCHF, we investigated the antiviral activity of cranberry extract against HAZV, a surrogate nairovirus model of CCHFV that can be handled in Level 2 Biosafety Laboratories (BSL-2). The results indicate that the cranberry extract exerts an antiviral activity against HAZV by targeting early stages of the viral replication cycle, including the initial adsorption to target cells. Although the details of the molecular mechanism of action remain to be clarified, the cranberry extract exerts a virucidal effect through a direct interaction with HAZV particles that leads to the subsequent impairment of virus attachment to cell-surface receptors. Finally, the antiviral activity of the cranberry extract was also confirmed for CCHFV. As a whole, the evidence obtained suggests that cranberry extract is a valuable candidate to be considered for the development of therapeutic strategies for CCHFV infections.

Excessive activation and proliferation of hepatic stellate cells (HSCs) is the most critical factor in liver fibrosis.Cranberry (Vaccinium macrocarpon) is berry-bearing with potential health benefits. Here, we reported the inhibitory effects of cranberry phytochemicals (CPS) on HSC activation and liver fibrogenesis. The results showed that CPS reduced cell viability and inhibited the TGFβ/Smad signaling pathway of HSCs in vitro. The therapeutic effects of CPS on HSC activation were further linked to the amelioration of CCl4-induced liver fibrosis in rats. CPS treatment reduced liver fibrosis, revived liver function (HYP, MDA, ALB, ALP, ALT, AST, and TBIL), and decreased inflammatory cytokines (IL-1, IL-6, and TNF-α) in a dose-dependent manner. Moreover, the expression levels of the TGFβ/Smad signaling pathway related genes, including TGF-β1, Smad2/3, p-Smad2/3, Col1α1, and α-SMA, were down-regulated by CPS. It is suggested that CPS may inhibit HSC activation and liver fibrosis by reducing the expression of inflammatory cytokines and inhibiting the TGFβ/Smad signaling pathway.

Background/Aim: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of primary brain tumor and a cornerstone in its treatment is radiotherapy (RT). However, RT for GBM is largely ineffective at clinically safe doses, thus, the study of radiosensitizers is of great significance.Materials and Methods: With accumulating evidence for the anticancer effect of compounds from cranberry, this study was designed to investigate if cranberry extract (CE) sensitizes GBM to RT in the widely used human glioblastoma cell line U87. We utilized clonogenic survival assays, cell proliferation assays, and caspase-3 activity kits. Potential proliferative and apoptotic molecular mechanisms were evaluated by reverse transcription-polymerase chain reaction.Results: We found that CE alone had little effect on the survival of U87 cells. However, RT supplemented by CE significantly inhibited proliferation and promoted apoptosis of U87 cells when compared with RT alone. The proliferation-inhibitory effect of RT/CE might be attributable to the up-regulation of p21, along with the down-regulation of cyclin B and cyclin-dependent kinase 4. This pro-apoptotic effect might additionally be attributable to the down-regulation of surviving.Conclusion: These results warrant further study of the potential radiosensitizing capacity of CE in glioblastoma and other cancer types.

Generating formulations for the delivery of a mixture of natural compounds extracted from natural sources is a challenge because of unknown active and inactive ingredients and possible interactions between them. As one example, natural cranberry extracts have been proposed for the prevention of biofilm formation on dental pellicle or teeth. However, such extracts may contain phenolic acids, flavonol glycosides along with other constituents like coumaroyl iridoid glycosides, flavonoids, alpha-linolenic acid, n-6 (or n-3) fatty acids, and crude fiber. Due to the presence of a variety of compounds, determining which molecules (and how many molecules) are essential for preventing biofilm growth is nontrivial to ascertain. Therefore, a formulation that could contain natural, unrefined, cranberry extract (with all its constituent compounds) at high loading would be ideal. Accordingly, we have generated several candidate formulations including poly(lactic-co-glycolic) acid (PLGA)-based microencapsulation of cranberry extract (CE15) as well as formulations including stearic acid along with polyvinylpyrrolidone (PVP) or Ethyl lauroyl arginate (LAE) complexed with cranberry extracts (CE15). We found that stearic acid in combination with PVP or LAE as excipients led to higher loading of the active and inactive compounds in CE15 as compared with a PLGA microencapsulation and also sustained release of CE15 in a tunable manner. Using this method, we have been able to generate two successful formulations (one preventative based, one treatment based) that effectively inhibit biofilm growth when incubated with saliva. In addition to cranberry extract, this technique could also be a promising candidate for other natural extracts to form controlled release systems.

Improving the longevity of composite restorations has proven to be difficult when they are bonded to dentin. Dentin demineralization leaves collagen fibrils susceptible to enzymatic digestion, which causes breakdown of the resin-dentin interface. Therefore, measures for counteracting the enzymatic environment by enhancing dentin collagen's resistance to degradation have the potential to improve the durability of dental composite restorations. This study aimed to evaluate the effects of polyphenol-rich extracts and a chemical cross-linker on the cross-linking interaction, resistance to digestion, and endogenous matrix metalloproteinase (MMP) activities of dentin collagen under clinically relevant conditions. Ten-microm-thick films were cut from dentin slabs of non-carious extracted human third molars. Following demineralization, polyphenol-rich extracts-including grape seed (GSE), green tea (GTE), and cranberry juice (CJE)-or chemical cross-linker carbodiimide with n-hydroxysuccinimide (EDC/NHS) were applied to the demineralized dentin surfaces for 30 s. The collagen cross-linking, bio-stabilization, and gelatinolytic activities of MMPs 2 and 9 were studied by using Fourier-transform infrared spectroscopy, weight loss, hydroxyproline release, scanning/transmission electron microscopy, and in situ zymography. All treatments significantly increased resistance to collagenase degradation and reduced the gelatinolytic MMP activity of dentin collagen compared to the untreated control. The CJE- and GSE-treated groups were more resistant to digestion than the GTE- or EDC/NHS-treated ones (p < 0.05), which was consistent with the cross-linking interaction found with FTIR and the in situ performance on the acid-etched dentin surface found with SEM/TEM. The collagen films treated with CJE showed the lowest MMP activity, followed by GSE, GTE, and, finally, EDC/NHS. The CJE-treated dentin collagen rapidly increased its resistance to digestion and MMP inhibition. An application of CJE as short as 30 s may be a clinically feasible approach to improving the longevity of dentin bonding in composite restorations.

Plant-based foods contain bioactive compounds such as polyphenols that resist digestion and potentially benefit the host through interactions with their resident microbiota. Based on previous observations, we hypothesized that the probiotic Lactobacillus plantarum interacts with cranberry polyphenols and dietary oligosaccharides to synergistically impact its physiology. In this study, L. plantarum ATCC BAA-793 was grown on dietary oligosaccharides, including cranberry xyloglucans, fructooligosaccharides, and human milk oligosaccharides, in conjunction with proanthocyanidins (PACs) extracted from cranberries. As a result, L. plantarum exhibits a differential physiological response to cranberry PACs dependent on the carbohydrate source and polyphenol fraction introduced. Of the two PAC extracts evaluated, the PAC1 fraction contains higher concentrations of PACs and increased growth regardless of the oligosaccharide, whereas PAC2 positively modulates its growth during xyloglucan metabolism. Interestingly, fructooligosaccharides (FOS) are efficiently utilized in the presence of PAC1, as this L. plantarum strain does not utilize this substrate typically. Relative to glucose, oligosaccharide metabolism increases the ratio of secreted acetic acid to lactic acid. The PAC2 fraction differentially increases this ratio during cranberry xyloglucan fermentation compared with PAC1. The global transcriptome links the expression of putative polyphenol degradation genes and networks and metabolic phenotypes.

Consumption of cranberries is associated with the putative effects of preventing urinary tract infections (UTIs). Cranberry proanthocyanidins (PAC) contain unusual double A-type linkages, which are associated with strong interactions with surface virulence factors found on UTI-causing bacteria such as extra-intestinal pathogenic Escherichia coli (ExPEC), depicting in bacterial agglutination processes. In this work, we demonstrated the efficacy of cranberry PAC (200 mug/mL) to agglutinate ExPEC (5.0 x 108 CFU/mL) in vitro as a selective interaction for the design of functionalized biosensors for potential detection of UTIs. We fabricated functionalized screen-printed electrodes (SPEs) by modifying with PAC-polyaniline (PANI) nanocomposites and tested the effectiveness of the PAC-PANI/SPE biosensor for detecting the presence of ExPEC in aqueous suspensions. Results indicated that the PAC-PANI/SPE was highly sensitive (limit of quantification of 1 CFU/mL of ExPEC), and its response was linear over the concentration range of 1-70,000 CFU/mL, suggesting cranberry PAC-functionalized biosensors are an innovative alternative for the detection and diagnosis of ExPEC-associated UTIs. The biosensor was also highly selective, reproducible, and stable.

The emergence and spread of extended-spectrum beta-lactamases (ESBLs), metallo-beta-lactamases (MBLs), or variant low-affinity penicillin-binding proteins (PBPs) pose a major threat to our ability to treat bacterial infection using beta-lactam antibiotics. Although combinations of beta-lactamase inhibitors with beta-lactam agents have been clinically successful, there are no MBL inhibitors in current therapeutic use. Furthermore, recent clinical use of new-generation cephalosporins targeting PBP2a, an altered PBP, has led to the emergence of resistance to these antimicrobial agents. Previous work shows that natural polyphenols such as cranberry-extracted proanthocyanidins (cPAC) can potentiate non-beta-lactam antibiotics against Gram-negative bacteria. This study extends beyond previous work by investigating the in vitro effect of cPAC in overcoming ESBL-, MBL-, and PBP2a-mediated beta-lactam resistance. The results show that cPAC exhibit variable potentiation of different beta-lactams against beta-lactam-resistant Enterobacteriaceae clinical isolates as well as ESBL- and MBL-producing E. coli. We also discovered that cPAC have broad-spectrum inhibitory properties in vitro on the activity of different classes of beta-lactamases, including CTX-M3 ESBL and IMP-1 MBL. Furthermore, we observe that cPAC selectively potentiate oxacillin and carbenicillin against methicillin-resistant but not methicillin-sensitive staphylococci, suggesting that cPAC also interfere with PBP2a-mediated resistance. This study motivates the need for future work to identify the most bioactive compounds in cPAC and to evaluate their antibiotic-potentiating efficacy in vivo.

Natural compounds are extensively used in the treatment of various diseases. Regular consumption of polyphenols plays an important role in the protection of health by reducing the risk of degenerative diseases, including cancer. The evaluation of the cytotoxic effect of the newly obtained multifruit polyphenolic preparation (composed of seven fruit) on T47D and MCF-7 breast cancer cells and MCF-12A normal cells. The PP was produced on the basis of combined ultrafiltrates obtained from chokeberry, raspberry, wild strawberry, apricot, peach, bilberry, and cranberry. The experiments were performed using human mammary gland cancer cell lines T47D (ductal cancer) and MCF-7 (adenocarcinoma) and normal breast cell line MCF-12A. Chromatographic techniques confirmed the highest contribution of cyanidin 3-O-glucoside, p-coumaroyl glucoside and chlorogenic acid in the PP. The PP exhibited dose-dependent cytotoxic effects towards MCF-7 and T47D cancer cell lines (IC50=1.2 g.cm-3) and MCF-12A cells (IC50=0.6 g.cm-3). The MTT cytotoxicity assay and microscopic observations confirmed the cytopathic effect of the PP on cell lines. It is supposed that berry polyphenols interfered with estrogen receptors leading to changes in the production of paracrine growth factors and therefore, PP was less cytotoxic towards the MCF-7 and T47D cell lines than against the MCF-12A cell line.