Health Benefits of Berries: Cranberries

In light of the continuing need for effective anticancer agents, and the association of fruit and vegetable consumption with reduced cancer risk, edible plants are increasingly being considered as sources of anticancer drugs. Cranberry presscake (the material remaining after squeezing juice from the berries), when fed to mice bearing human breast tumor MDA-MB-435 cells, was shown previously to decrease the growth and metastasis of tumors. Therefore, further studies were undertaken to isolate the components of cranberry that contributed to this anticancer activity, and determine the mechanisms by which they inhibited proliferation. Using standard chromatographic techniques, a warm-water extract of cranberry presscake was fractionated, and an acidified methanol eluate (Fraction 6, or Fr6) containing flavonoids demonstrated antiproliferative activity. The extract inhibited proliferation of 8 human tumor cell lines of multiple origins. The androgen-dependent prostate cell line LNCaP was the most sensitive of those tested (10 mg/L Fr6 inhibited its growth by 50%), and the estrogen-independent breast line MDA-MB-435 and the androgen-independent prostate line DU145 were the least sensitive (250 mg/L Fr6 inhibited their growth by 50%). Other human tumor lines originating from breast (MCF-7), skin (SK-MEL-5), colon (HT-29), lung (DMS114), and brain (U87) had intermediate sensitivity to Fr6. Using flow cytometric analyses of DNA distribution (cell cycle) and annexin V-positivity (apoptosis), Fr6 was shown in MDA-MB-435 cells to block cell cycle progression (P < 0.05) and induce cells to undergo apoptosis (P < 0.05) in a dose-dependent manner. Fr6 is potentially a source of a novel anticancer agent.

A diet rich in fruit and vegetables is associated with decreased risk of disease. One possible mechanism for this is that dietary antioxidants positively regulate protective genes. Toward our goal to identify bioactive compounds with such functions in plants, we developed transgenic mice that express luciferase controlled by the gamma-glutamylcysteine synthetase heavy subunit (GCS(h)) promoter. Mice that consumed a nonpurified diet ad libitum were supplemented with juices or extracts of antioxidant-rich berries for 42 h or 3-4 wk. The treatments generally increased luciferase activity in brain and skeletal muscle and decreased it in liver compared with controls fed water. The same overall pattern was also found in mice fed ellagic acid (EA), a phenolic acid found in many berries. This change in GCS(h) promoter activity after berry treatment occurred in only approximately 50% of the mice, indicating that they were either responders or nonresponders. Our results demonstrate for the first time that berry extracts rich in polyphenols and EA can induce GCS(h) in vivo. The induction of protective enzymes may be important for the chemopreventive effects of fruits and vegetables.

OBJECTIVE:  It is well known that eradication of Helicobacter pylori infection results in healing of peptic ulcer and regression of gastric mucosal inflammation. Cranberry juice beverages have been shown to achieve good results in the prevention of recurrent urinary tract infection. The present study aimed to investigate whether a cranberry juice cocktail could eradicate or prevent H. pylori infection in mice.

 METHODS:  In the therapeutic trial, C57BL/6 mice were infected with H. pylori and 2 weeks later, 80 mice were randomly allocated into four groups: Group A, cranberry juice (0.5 mL/mouse, p.o. daily for 30 days); Group B, triple therapy (amoxycillin 50 mg/kg, bismuth subcitrate 6.15 mg/kg, and metronidazole 22.5 mg/kg, daily for 14 days); Group C, a combination of cranberry juice and triple therapy; Control Group, the mice were infected with H. pylori and left untreated. The mice were killed after 24 h and 4 weeks and H. pylori infection status was assessed by rapid urease test and by culture and histology, respectively. In the prevention trial, 40 mice had oral cranberry juice for 30 days. In the last 5 days (days 2630), the mice were divided into four groups: Group A, challenged orally with H. pylori three times on days 26, 28 and 30 when the mice were not given cranberry juice; Group B, challenged with H. pylori suspended in cranberry juice; Group C, challenged with H. pylori 6 h after receiving juice; Control group, no cranberry juice, but challenged with H. pylori. Two weeks later, the mice were killed to assess the status of H. pylori infection.

 RESULTS:  The clearance rates at 24 h after treatment in groups A, B and C were 80%, 100%, and 90%, respectively (P < 0.01 as compared with Control group, two tailed Fisher's Exact Probability Test). Four weeks after cessation of treatment the eradication rates in groups A, B and C were 20% (P = 0.474, two tailed Fisher's Exact Probability Test), 80% and 80%, respectively (P < 0.01). None of the mice were clear of H. pylori infection.

 CONCLUSIONS:  Cranberry juice can clear H. pylori infection in mice with a clearance rate of 80%, but the eradication rate was low (20%). Cranberry juice was not effective in preventing H. pylori infection in the mice used in this study.

Fruit and specific components within fruit are being associated with human health attributes, such as maintenance of urinary tract health and antioxidant status. Previous analyses of chemical constituents in cranberry fruit have been limited to a small number of compounds and have utilized the fruit from relatively few cultivars. Furthermore, recent DNA fingerprinting studies have revealed a high level of varietal misidentification within cranberry cultivars, which may have complicated the interpretation and conclusions from the previous studies. A comprehensive collection of cranberry germplasm, including domesticated and undomesticated varieties, has been established and is being maintained in genetically homogeneous field plots. Fruit samples were collected over two harvest dates in 1998 from over 390 producing germplasm plots. Horticultural (yield, fruit size, fruit rot, etc.) and fruit chemistry traits were evaluated. Fruit chemistry traits included total phenolics, total and individual anthocyanins, proanthocyanidins, soluble solids, titratable acidity, quinic acid, citric acid, malic acid, and individual sugars. Significant genetic variability was found for overall phenolic, anthocyanin and proanthocyanidin levels as well as for specific phenolics, organic acids and sugars. The levels of phenolic compounds within fruit are negatively correlated with horticultural traits such as yield, fruit size, etc. Varieties having unique chemistry profiles offer genes for breeding varieties with desired fruit chemistry profiles for enhanced health attributes.

Several forces are driving an expanded use of nutraceuticals, particularly functional foods and probiotics, as instruments of the restoration and maintenance of well-being. These include consumer desire to use natural rather than pharmaceutical products, the mounting scientific evidence that shows efficacy of certain nutraceutical products, and the increasing cost and continued failure of drugs to cure or prevent disease. There is now a strong scientific basis for use of cranberries to reduce the risk of E. coli adhesion to bladder cells and the onset of urinary tract infection. There is also a mechanistic basis and clinical support for use of Lactobacillus strains such as L. rhamnosus GR-1 and L. fermentum RC-14 to colonize the intestine and vagina and reduce the risk of intestinal and urogenital infections. For such alternative approaches to be successful, scientific rigor must be backed by public education and physician acceptance. Given the emergence of virulent and multidrug-resistant pathogens, time is not on our side.

"One of the major health benefits attributed to the ingestion of cranberry juice is the maintenance of urinary tract health. Traditionally, the juice was thought to cause acidification of the urine resulting in a bacteriostatic effect. However, recent research has demonstrated that a bacterial antiadhesion mechanism is responsible. Proanthocyanidins with unique molecular structures have been isolated from cranberry fruit that exhibit potent bacterial antiadhesion activity.”

Urinary tract health benefits have long been ascribed to the American cranberry, Vaccinium macrocarpon , through folklore. Now, a growing body of science supports this association. Current research suggests that this benefit is due to components in cranberry preventing the adhesion of certain bacteria in the urinary tract. Cranberry's relatively unique A-type proanthocyanidins were identified as the compo-nents that prevented the adhesion of P-fimbriated E. coli to uroepithelial cells using bioassay-directed fractionation techniques. Very recently, using an animal model, in vivo evidence was obtained suggesting that cranberry proanthocyanidins were absorbed and elicited this specific anti-adherence activity in urine. Recent preliminary research suggests that cranberry's microbial anti-adhesion effect may extend into the gastrointestinal tract, which may contribute to both the urinary tract health benefit as well as preventing attachment of H. pylori , the bacteria responsible for many peptic ulcers. Diets high in fruits, vegetables, and grains contribute to improving health status in a number of ways. Oxidative stress may play a role in the development of many chronic diseases, including cardiovascular diseases. Ex vivo testing indicates that cranberry flavonoids inhibit the oxidation of human LDL cholesterol, with proanthocyanidins the most active flavonoid fraction. Additionally, a diet rich in cranberry juice powder significantly reduced the total and LDL cholesterol in hypercholesteremic pigs. Cranberry appears to be a relatively unique fruit in that it may provide benefits both through microbial anti-adhesion and possibly through antioxidant mechanisms.

The American cranberry (Vaccinium macrocarpon) has a rich history. A growing body of science now supports the role of the cranberry in maintaining urinary tract health. Although it has been commonly believed that cranberries promote urinary tract health by acidifying the urine, research best supports a mechanism of antiadhesion against certain urinary pathogens. New preliminary research suggests that this microbial antiadhesion effect may show promise in other parts of the body, including the oral cavity and gastrointestinal tract. A growing body of research suggests that cranberry is a relatively unique fruit because it may provide two different pathways to health: through microbial antiadhesion and broader benefits that may be related to antioxidant activities.