BACKGROUND: Cranberry proanthocyanidins (c-PAC) are oligomeric structures of flavan-3-ol units, which possess A-type interflavan bonds. c-PAC differs from other botanical sources because other PAC mostly have B-type interflavan bonds. Cranberry products used to alleviate and prevent urinary tract infections may suffer from adulteration, where c-PAC are replaced with less expensive botanical sources of PAC that contain B-type interflavan bonds.OBJECTIVE: Identifying the presence of A-type interflavan bonds in cranberry fruit and dietary supplements.METHODS: Thirty-five samples reported to contain A-type PAC (cranberry fruit and cranberry products) and 36 samples reported to contain B-type PAC (other botanical sources) were identified and differentiated using MALDI-TOF MS, deconvolution of overlapping isotope patterns, and principal component analysis (PCA).RESULTS: Our results show that both MALDI-TOF MS and deconvolution of overlapping isotope patterns were able to identify the presence of A-type interflavan bonds with a probability greater than 90% and a confidence of 95%. Deconvolution of MALDI-TOF MS spectra also determined the ratio of A-type to B-type interflavan bonds at each degree of polymerization in cranberry fruit and cranberry products, which is a distinguishing feature of c-PAC in comparison to other botanical sources of PAC. PCA shows clear differences based on the nature of the interflavan bonds.CONCLUSIONS: MALDI-TOF MS, deconvolution of overlapping isotope patterns of MALDI-TOF MS spectra, and PCA allow the identification, estimation, and differentiation of A-type interflavan bonds in cranberry-based foods and dietary supplements among other botanical sources containing mostly B-type interflavan bonds.

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects..

Lead (Pb) has been identified as a hazardous heavy metal and a pollutant in the environment, especially due to its human activity. It poisons several physiological systems, such as the hepatic, renal, reproductive, as well as nervous systems, because of an elevation in oxidative damage caused by the formation of reactive oxygen species (ROS). Cranberry is a powerful antioxidant in addition to being a component of an anti-inflammatory disease treatments. The goal of this study was to see if cranberry extract could protect rats from toxicity caused by lead acetate. Addition of cranberry extract at a dose of 75 and 150 mg/kg to rats allowed to treat with lead acetate at a dose of 50 mg/kg to 6 weeks significantly protected the rats from the lead acetate-induced increase in both serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenases (LDH), total and direct bilirubin, alkaline phosphatase (ALP), creatinine, urea, total cholesterol (TC), triglycerides (TG), LDL-C and VLDL-C in addition against an elevation of serum glucose, tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA).Treatment with cranberry extract at a dose of 75 and 150 mg/kg also led to a valuable rise in serum total soluble protein, albumin, globulin, HDL-C, triiodothyronine (T3), total thyroxine (T4) as well as hepatic and renal tissue of reduced glutathione (GSH), superoxide dismutase (SOD), catalase activity (CAT) and total antioxidant capacity (TAC) as compared to lead acetate-treated rats. Cranberry has hepato-renal protective impacts in restoring liver and kidney function, according to histopathological evaluation of hepatic and renal tissues. These findings have shown, in conclusion, that cranberry extract has such a strong protective effect in rats suffering from hepato-renal toxicity caused by lead acetate.

Functional plant-based foods (such as fruits, vegetables, and berries) can improve health, have a preventive effect, and diminish the risk of different chronic diseases during in vivo and in vitro studies. Berries contain many phytochemicals, fibers, vitamins, and minerals. The primary phytochemicals in berry fruits are phenolic compounds including flavonoids (anthocyanins, flavonols, flavones, flavanols, flavanones, and isoflavonoids), tannins, and phenolic acids. Since berries have a high concentration of polyphenols, it is possible to use them for treating various diseases pharmacologically by acting on oxidative stress and inflammation, which are often the leading causes of diabetes, neurological, cardiovascular diseases, and cancer. This review examines commonly consumed berries: blackberries, blackcurrants, blueberries, cranberries, raspberries, black raspberries, and strawberries and their polyphenols as potential medicinal foods (due to the presence of pharmacologically active compounds) in the treatment of diabetes, cardiovascular problems, and other diseases. Moreover, much attention is paid to the bioavailability of active berry components. Hence, this comprehensive review shows that berries and their bioactive compounds possess medicinal properties and have therapeutic potential. Nevertheless, future clinical trials are required to study and improve the bioavailability of berries' phenolic compounds and extend the evidence that the active compounds of berries can be used as medicinal foods against various diseases.

Cranberry is a popular ingredient in dietary supplements in the U. S. and is commonly used for preventing urinary tract infections. Because of its popularity in dietary supplements, the U. S. Pharmacopeial Convention has developed quality standards for cranberry ingredients. The purpose of this review was to determine if there are safety issues that should preclude the admission of cranberry ingredients from the development of U. S. Pharmacopeial Convention quality standards. Based on the totality of the data, the U. S. Pharmacopeial Convention concluded that cranberry ingredients are not known to be associated with serious risks to human health when consumed properly in dietary supplements and therefore were admitted for standard development. Although published clinical and animal data indicated that cranberry is not associated with serious adverse effects, interactions with warfarin and kidney stone formation were identified as potential risks. Studies have reported contradictory data regarding the role of cranberry in kidney stone formation, with some reports suggesting cranberry is associated with a reduced risk of kidney stones. Interactions with warfarin were not associated with moderate intakes of cranberry juice (240 - 480 mL). Some reports suggested that the potential for warfarin interactions requires excessive intakes of cranberry juice (1 - 2 L/day) or cranberry extracts (3000 mg/day). Cases of warfarin interactions with cranberry have mostly involved patients with serious illnesses and/or individuals taking concomitant medications. Based on these findings, the U. S. Pharmacopeial Convention concluded that the use of cautionary labeling statements regarding interactions with warfarin or kidney stone formation is not necessary in the development of quality standards for cranberry ingredients.

The non-dialyzable material (NDM) of polyphenol-rich cranberry extract (CRE) powder (NDM-CRE) was studied for its effect of inducing body weight (BW) loss in 13 different mouse lines with well-defined genetically diverse backgrounds, named the collaborative cross (CC). From the age of 8 weeks, the mice were maintained on a high-fat diet (HFD) for 18 weeks, to induce obesity, and BW was measured biweekly. From week 12, CRE was injected intraperitoneally (IP) (50 mg kg-1) 3 times a week per mouse for a 6 week period. Statistical analysis results have shown a significant increase in body weight between week 0 and week 12; the increase in BW of 13 lines of mice on HFD was in the range of 10.41% to 68.65% for males and 9.78% to 64.74% for females. After injecting NDM-CRE extract, our analysis has shown an induced change in BW between week 12 and week 18. In males, NDM-CRE caused a significant decrease in BW of 5 out of the 13 lines in the range of -5.68% to -16.69% and a significant increase of 8.31% in BW of one male line, whereas in seven lines there was no significant decrease (-2.14% to -4.09%). In females, NDM-CRE caused a significant decrease in BW of 5 out of the 13 lines in the range of -3.90% to -11.83%, whereas in eight lines there were no significant changes in BW and it ranged between -1.50% and 4.90%. The broad-sense heritability (H2) and genetic coefficient of variation (CVg) were estimated and found to be between 0.71 and 0.81 for H2, and 0.18 and 0.24 for CVg of females and males, respectively, with respect to the efficacy of NDM-CRE on body weight reduction. Our results have shown that hosts with different genetic backgrounds respond differently to body weight increase, as well as to NDM-CRE treatment for body weight reduction. These results provide a platform for assessing more CC lines and mapping genes underlying the efficacy of the NDM-CRE treatment as a way of understanding pharmacogenomics.

Lead poisonousness is a widely recognized type of heavy metal poisoning in humans and animals. So, this study aimed to assess the ameliorative role of cranberry extract use on hematological changes induced by lead acetate in rats. A total number of 40 adult male albino rats weighing approximately 200 +or- 20 g were randomly assigned into four groups; Normal control group, group 2; Positive control, lead acetate at a dose of (50 PPM) for 45 days, group 3; Lead acetate at a dose of (50 PPM) then Cranberry extract (75 mg/kg) for 45 days also group 4; Lead acetate (50 PPM) then Cranberry extract (150 mg/kg) for 45 days. Blood samples were collected in EDTA tubes for hematological examinations. Oral administration of lead acetate (50 PPM) significantly decreased total erythrocyte count, hemoglobin, packed cell volume and mean cell volume levels in comparison with the normal control group (P< 0.0001). Addition of cranberry extract at a dose of 75 and 150 mg/kg significantly increased the total erythrocyte count, hemoglobin, packed cell volume and mean cell volume levels in comparison with the positive control group (P< 0.0001). Oral administration of lead acetate (50 PPM) significantly increased total leukocytes count, lymphocyte, neutrophils, eosinophil and monocytes count in comparison with the normal control group (P< 0.0001). Addition of cranberry extract at a dose of 75 and 150 mg/kg significantly decreased the total leukocytes count, lymphocyte, neutrophils, eosinophil and monocytes count in comparison with the positive control group (P< 0.0001). Our results clearly indicate that cranberry extract ameliorates hematological changes in lead acetate-treated rats

The prevalence of obesity in the world is fearsomely climbing, which has brought about heavy threats on human health and economic development. For coping with this problem, researchers have looked at the profound potentials of natural products for resolving obesity because of their high efficiencies and few undesirable outcomes in the recent years. Berry fruits are huge reservoirs of bioactive components, and their anti-obesity potentials are arousing much interests. In this review, the current main strategies to manage obesity were summarized, including inhibiting appetite and lowering the food intake, improving energy expenditure and thermogenesis, suppressing absorption and digestion, reducing lipid synthesis and storage as well as modulating composition of gut microbiota. In addition, this review discussed the potentials of dietary berry fruits (blueberries, cranberries, raspberries, strawberries, mulberries, lingonberries, blackberries, black chokeberries, elderberries, bilberries, grape, blackcurrants, jaboticabas, red bayberries, sea-buckthorns, goldenberries and goji berries) to counteract obesity or obesity-associated complications based on recent animal experiments and human studies. Then, the bioaccessibility of phenolic compounds present in berry fruits was discussed. On the other hand, several challenges including securing effective dosage, further understanding their interaction with human tissues, improving bioavailability and protection of functional ingredients during delivery should be taken into account and conquered in the coming years.

Due to rising consumer preference for natural remedies, the search for natural antiviral agents has accelerated considerably in recent years. Among the natural sources of compounds with potential antiviral proprieties, berries are interesting candidates, due to their association with health-promoting properties, including antioxidant, antimutagenic, anticancer, antimicrobial, anti-inflammatory, and neuroprotective properties. The past two decades have witnessed a flurry of new findings. Studies suggest promising antiviral proprieties against enveloped and non-enveloped viruses, particularly of cranberries, blueberries, blackcurrants, black raspberries, and pomegranates. The aim of this review is to assemble these findings, to list the implied mechanisms of action, and thereby point out promising subjects for research in this field, in the hope that compounds obtainable from natural sources such as berries may be used someday to treat, or even prevent, viral infections.

The microbiome plays a major role in polyphenol metabolism, producing metabolites that are bioavailable and potentially more bioactive than the compounds from which they are derived. However, the microbiome can vary among individuals, and especially for those with co-morbidities, such as ulcerative colitis. In subjects with ulcerative colitis, the consequence of a 'dysbiotic' microbiome is characterized by decreased diversity of microbiota that may impact their capability to metabolize polyphenols into bioavailable metabolites. On this premise, the microbiome metabolism of cranberry polyphenols between healthy individuals and those with ulcerative colitis was compared in vitro. Fecal samples from volunteers, with or without diagnosed ulcerative colitis, were cultured anaerobically in the presence of cranberry polyphenols. The resulting metabolites were then quantified via LC-ESI-MS/MS. 16S rRNA metagenomics analysis was also utilized to assess differences in microbiota composition between healthy and ulcerative colitis microbiomes and the modulatory effects of cranberry polyphenols on microbiota composition. Healthy microbiomes produced higher (p < 0.05) concentrations of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone and 3-hydroxyphenylacetic acid in comparison to ulcerative colitis microbiomes. Additionally, healthy microbiomes contained a higher (p < 0.05) abundance of Ruminococcaceae, which could explain their ability to produce higher concentrations of cranberry polyphenol metabolites. Health status and the presence of cranberry polyphenols also significantly impacted the production of several short-chain and branched-chain fatty acids. These results suggest that efficiency of polyphenol metabolism is dependent on microbiota composition and future works should include metabolite data to account for inter-individual differences in polyphenol metabolism.