Pomegranate and Its Modern Research Update:

  seminal trace...Pomegranate Seed Extract.Polyphenols 40%80%.Pomegranate Hull Extract,Ellagic Acid 90%.CAS.RN.NO:84961-57-9.90045-46-8.Punica granatum,Pomegranate Extract.Guava Extract....

   Phytochemical info of Pomegranate Seed Extract and Pomegranate Hull Extract:

 Product Name:
 Synonym:
 Definition: Pomegranate Seed Extract.Pomegranate Hull Extract are majorly composed of
 Chemical information disclosed as following table:


   Research update of Pine Bark Extract Proanthocyanidins related.:

   Pomegranate seed may cause breast cancer cells to self-destruct:
 Israeli researchers have found that pomegranates could have important implications for breast cancer treatment and the safety of oestrogen replacement therapy.
 Technion-Israel Institute of Technology found that pomegranate seed oil triggers apoptosis, a self-destruct mechanism, in breast cancer cells. In addition, pomegranate juice can be toxic to most oestrogen-dependent breast cancer cells, while leaving normal breast cells largely unaffected.
 

   Oestrogen is a hormone prescribed to protect postmenopausal women against heart disease and osteoporosis:

 "Pomegranates seem to replace the oestrogen often prescribed to protect postmenopausal women against heart disease and osteoporosis, while selectively destroying dependent-dependent cancer cells," explains Dr. Ephraim Lansky, who headed the studies.
 In the first study, laboratory-grown breast cancer cells were treated for three days with pomegranate seed oil. The researchers observed apoptosis in 37 to 56 per cent of the cancer cells, depending on the dose of oil applied.
 In the second study, both normal and cancerous breast cells were exposed to pomegranate wine and pomegranate peel extracts, which contain polyphenols. The vast majority of the normal cells remained unaffected by the two pomegranate derivatives. But more than 75 per cent of the oestrogen-dependent cancer cells, and approximately half of the non-oestrogen dependent cancer cells were destroyed by exposure to these same pomegranate products.
 Dr. Martin Goldman, a New York-based board certified internist and life medicine specialist, notes, "this is apparently a safe substance that could be helpful to many people, especially women at high-risk for developing breast cancer."
 According to Dr. Lajos Pusztai, an assistant professor who studies breast cancer at the M.D. Anderson Cancer Centre in Houston, Dr. Lansky's study "provides a potential new avenue to develop anti-cancer drugs from a natural compound."
 Technion researchers have tested other health benefits of pomegranates, showing their antioxidant potency and ability to lower oxidation of LDL cholesterol, leading to the elimination of plaques in arteries.
 

   Pomegranate Power:Researchers discover the phytochemical potential in this ancient fruit:

 Pomegranates have been cultivated since prehistoric times. These extraordinary fruits have also appeared throughout history as symbols of fertility, royalty, hope, and abundance. Celebrated in art, mythology, religious texts and literature for centuries, pomegranates appear in Greek mythology, Egyptian papyrus, and have been mentioned in the Old Testament several times under the name of rimmon. An ancient fruit, the pomegranate was brought to China a century and a half before the Christian era. The pomegranate is depicted on floor mosaics of Pompeii.
 The word pomegranate is derived from Middle French pome garnete and literally means "seeded apple." The average pomegranate can contain as many as 800 seeds, and due to its profusion of seeds, the ancients connected the pomegranate with procreation and abundance, and they believed the goddess Aphrodite, deity of love, had planted it on the isle of Cyprus. It was because of the tiny, red pomegranate seed that Demeter's daughter, Persephone, was carried off by Hades to live a life divided between the underworld and the upper world. This much lauded fruit, however, hasn't quite supplanted the apple in popularity in American fare. And perhaps it should, considering recent preliminary studies extolling the health benefits of pomegranates. In fact, current studies suggest that these hardy, ancient fruits could become the next superfood.
 Adel A. Kader, Ph.D., Professor of Postharvest Physiology, Department of Pomology at the University of California, has conducted research on the phytochemical profile of pomegranates, and states that "our research indicates that the total antioxidant capacity of 100 ml of pomegranate juice is two to three times that of 100 ml of red wine and of 100 ml of green tea. This is due to the higher polyphenols content of pomegranates."
 A recently published article, "Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids," conducted at Israel's Institute of Technology (J Ethnopharmacol, July 1999) indicates that pomegranates contain flavonoids that are more concentrated than those found in grapes. Researchers examined the enzyme inhibition properties of pomegranate fermented juice and seed oil. The pomegranate fermented juice and cold-pressed seed oil showed strong antioxidant activity close to that of butylated hydroxyanisole (BHA) and green tea, and significantly greater than that of red wine. The investigators showed that pomegranate seed polyphenols possess potent antioxidant and most likely cardiovascular and anti-inflammatory effects as well. If consumed daily over a long period of time, the powerful antioxidants in pomegranates may help to combat cancer, and may also prevent hardening of the arteries.
 Other studies show that pomegranate seeds contain a number of flavonoids, including isoflavones with estrogenic capabilities. Flavonoids are part of a wide class of polyphenolic compounds that posses an impressive array of pharmacological activities. Researchers in England are studying the possibility of developing a virucide from pomegranates as a protective anti-viral agent against HIV.
 In India, a preliminary study screening for antimicrobial activities of pomegranate seeds shows them to have potent antimicrobial activities against laboratory test organisms Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae. While more studies are needed to further investigate the nutritional power of pomegranates, the nutritional significance of this ancient fruit is just beginning to emerge.
 

   Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids:

 Laboratories of Food Engineering and Biotechnology, Technion-Israel Institute of Technology, Haifa.
 The antioxidant and eicosanoid enzyme inhibition properties of pomegranate (Punica granatum) fermented juice and seed oil flavonoids were studied. The pomegranate fermented juice (pfj) and cold pressed seed oil (pcpso) showed strong antioxidant activity close to that of butylated hydroxyanisole (BHA) and green tea (Thea sinensis), and significantly greater than that of red wine (Vitis vitifera). Flavonoids extracted from pcpso showed 31-44% inhibition of sheep cyclooxygenase and 69-81% inhibition of soybean lipoxygenase. Flavonoids extracted from pfj showed 21-30% inhibition of soybean lipoxygenase though no significant inhibition of sheep cyclooxygenase. The pcpso was analyzed for its polyphenol content and fatty acid composition. Total polyphenols in pcpso showed a concentration by weight of approximately 0.015%. Pcpso fatty acid composition showed punicic acid (65.3%) along with palmitic acid (4.8%), stearic acid (2.3%), oleic acid (6.3%), linoleic acid (6.6%) and three unidentified peaks from which two (14.2%) are probably isomers of punicic acid (El-Shaarawy, M.I., Nahpetian, A., 1983). Studies on pomegranate seed oil. Fette Seifen Anstrichmittel 83(3), 123-126).
 


   Pomegranate's antioxidant properties:

 Just because pomegranate has gained newsworthiness of late, we should not forget its considerable primary antioxidant powers or less sensational plaudits as a preventive health drink. Whatever else pomegranate contains that may be applicable to specific diseases and conditions, modern scientific interests all stems from that strong force for good.
 Back in 1999 Israeli research on pomegranate's juice and cold pressed seed oil first showed strong antioxidant activity close to that of (butylated hydroxyanisole [BHA]) and green tea, and significantly greater than that of red wine.
 It has already been established that antioxidant activity in pomegranate juices is higher when extracted from whole pomegranates than in experimental juices obtained from the luscious red arils only. Not forgetting the red fruits anthocyanidins (red pigment) that contribute to the antioxidant activity, pomegranate juice has superior bioactivity compared to its purified polyphenols, which illustrates how the chemical synergy of the whole fruit multiple compounds compared to single, purified, active ingredients may prove to be preferable.
 In the lab-to-mouth process, research into the antioxidant properties of extracts from pomegranate peel and seeds results have been so encouraging that they are likely to be exploited via applications for the preservation of food products, as well as health supplements and neutraceuticals.
 Delicious pomegranate juice, bursting with antioxidants, is now said to contain in one glass as many antioxidants as two glasses of red wine or ten cups of green tea! It is also packed with vitamins A, C and E, and folic acid, the latter being important in the first trimester of pregnancy.
 Another important aspect of polyphenol-rich pomegranate juice is that results in animal models show that dietary supplementation with pomegranate juice is neuro-protective for the neonatal brain, which affects the infant during the first month after birth. It is worth noting in relation to any forthcoming supplements that pomegranate peel has a high polyphenolic content. A gel made from the peel has also demonstrated wound-healing capacity.
 

   Pomegranate, floral medicine and diabetes:

 The pomegranate really does have a most beautiful flower and this part of the amazing plant is no less interesting or medicinally exciting. The use of the flower has been recommended in Unani, an ancient and most natural form of medicine, as a remedy for diabetes.
 Earlier last year Australian researchers found that their scientific investigation of pomegranate flower extract improved hyperglycaemia in Type II diabetes and obesity, at least partially. Last autumn, further phytochemical investigation demonstrated that pomegranate flower extract's gallic acid is mostly responsible for its glycaemic activity. This was good news because it will help toward a better understanding of the extract's therapeutic mechanism and potential.
 Last autumn a human study by Iranian researchers found that concentrated pomegranate juice (CPJ) improves lipid profiles in diabetic patients with hyperlipidemia, ie. the presence of excess lipids in the blood. They concluded that CPJ consumption may modify heart disease risk factors in hyperlipidemic patients and therefore its inclusion in their diets may be beneficial.
 Additionally, research findings on excess triglyceride accumulation and increased fatty acid oxidation in the diabetic heart, which contribute to cardiac dysfunction, suggested that pomegranate flower extract improves abnormal cardiac lipid metabolism, thereby aiding heart function.
 


   Pomegranate the Anticarcinogenic:

 In October, 2005, Australian pop-singer Kylie Minogue, after her own devastating diagnosis for breast cancer, with great positivity helped raise the profile of breast cancer; but we must never forget that men can get this form of cancer too.
 It is good to know that, as well as pomegranate's potential non-cytotoxic therapy for leukaemia25 (pomegranate fermented juice, pericarp extracts and 'fatty acids' from seed oil), flavonoid-rich polyphenol fractions from pomegranate fruit have been shown to exert anti-proliferative, anti-invasive, anti-eicosanoid and pro-apoptotic actions in breast and prostate cancer cells and other solid malignancies.
 The roseate fruit is exceptional in that various parts of the fruit, eg. seed oil, juice, fermented juice and peel extract have been shown to exert suppressive effects on human breast cancer cells in vitro.
 Four years ago, in Korea, in laboratory testings of pomegranate as a chemo-preventive against breast cancer, it was found that pomegranate seed oil had the edge on cancer cell line death (apoptosis), ranging from 90 percent inhibition of proliferation of (MCF-7) at 100 microg/ml medium and other results at 75 percent, and 54 percent apoptosis (cell death) at 50 microg/ml. In another test pomegranate fermented juice polyphenols effected 47 percent inhibition of cancerous lesion formation, suggesting further clinical trials were warranted.
 However, more recent American research interest in pomegranate's potential for aiding breast cancers (Summer, 2004) has shown the fruit as an anti-carcinogen to be very useful indeed. In fact, results highlight enhanced breast cancer preventive potential both for a purified compound and for pomegranate seed oil, both greater than that previously reported for pomegranate fermented juice polyphenols.
 

   Prostate cancer:

 Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among US males, with a similar trend in many Western countries like the UK. In fact, prostate cancer is now the most common cancer diagnosed in UK men. Every year over 30,000 men are diagnosed and 10,000 men die from it.
 One approach to control this malignancy is its prevention through the use of agents present in human diet. 'Lifestyle and diet' is important to all areas of health, but recently a randomized, controlled trial involving 93 men with biopsy-proven, untreated prostate cancer, suggested changes in lifestyle and diet can make considerable in-roads into the prevention of prostate cancer in men and even reverse its progression. A good move into changing diet would be for men to drink pomegranate juice.
 Although it is early days, a Wisconsin team first tested pomegranate juice with its strong antioxidant and anti-inflammatory properties on laboratory cultures of human prostate cancer cells. They found the extract killed the cancer cells and the higher the dose, the more cells died. Animal testing proved the juice to 'slow' tumour growth. Researchers suggested that pomegranate juice may not only have cancer-protective effects, but also chemotherapeutic effects against prostate cancer in humans. Further research is required, but as a recommendation from man to man it was stated: "It is not too soon to point out that diet is plainly significant in the development of prostate cancer. As there are sound reasons for adopting a healthy diet with generally increased intake of fruit and vegetables, why not consider pomegranate, and its juice, as one of the ways of achieving this."
 

 Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer:
 Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 microg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-X(L) and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rnu1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans.

   Skin cancer:

 On a lighter note, pomegranate is one of the most important botanicals pertaining to dermatologic uses, eg. botanical-based cosmeceuticals. Dermatological scientists have published clinical trials for the treatment of parameters of extrinsic ageing, such as environmental damage. More importantly, topical application of pomegranate fruit extract tested on mouse skin appears to exhibit protective action in skin tumours. Furthermore, pomegranate seed oil has an excellent profile and a couple of years ago topical application for possible skin cancer protective efficacy was investigated. The overall results highlighted the potential of the seed oil as a 'safe' and effective protective agent against skin cancer.
 This is excellent news because skin cancer is also one of the most common cancers in the UK and the number of people who get it is increasing. The number of cases has more than doubled since the early 1980s. There are over 69,000 new cases of skin cancer diagnosed each year in the UK; many are not reported so the real number is probably much higher. Over 2,000 people die from skin cancer each year. The significant fact is that there are proportionately more skin cancer deaths in the UK than in Australia, so it is likely there will be even greater interest and research into pomegranate's products coming from that quarter before long.


   Cancer of the mouth and oesophagus:

 Just as TV Chef Rick Stein is following the canal system of France learning and sampling the delights of fresh regional food, so the cancer curative properties and potential of pomegranate follow the human alimentary canal. Cancer of the mouth, once rare, is increasingly noticeable. Cancer of the oesophagus has a more varied geographical distribution and incidence than any other commonly occurring cancer. Its incidence rate is increasing in many countries, especially among males.
 Although oesophageal cancer has been found to be associated with the consumption of alcohol and tobacco, particularly when combined, in the last decade the role of nutrition and diet in the etiology of this disease has attracted worldwide attention, 'Regions with a large incidence of this disease are generally located in poor parts of the world, and their inhabitants share several dietary characteristics. They subsist on a diet high in starch and almost without fresh fruit or vegetables, eat rapidly without sufficient mastication, and consume many foods and drinks such as tea at very high temperatures.
 Unfortunately, in the West, diet and eating and drinking habits do in many instances comply with this dietary deficit pattern, but by choice! And again, in a dietary survey carried out as long ago as 1987 ¡®in Mazanderan Province of the Caspian Littoral of Iran, where the inhabitants have the highest rate of esophageal cancer in the world, ¡­ they drink more tea at a much higher temperature [and] very little fruit and vegetables are consumed by [those] of the high-risk region, whereas inhabitants in the low-risk area keep vegetables and citrus fruits as an important part of their usual diets.
 Mouth cancer can affect the lips, tongue, cheeks and throat, which condition is also linked to poor diet! It kills 1,700 people in the UK every year and some 4,300 new cases are diagnosed annually. Men are still twice as likely to develop mouth cancer, but it has also become increasingly common in women in the last 10 years. Whereas previously it was thought that older people were particularly vulnerable to the disease, binge drinking and smoking may be fuelling an increase in mouth cancer among young people.
 Anecdotally, in the Middle East, Iran and India, healers use the bark, leaves and skin and rind as well as the edible parts of pomegranate to cure everything from conjunctivitis to haemorrhoids, eg. a paste of the leaves massaged into the scalp is said to reverse baldness. However, it is a boiled infusion of pomegranate rinds that is used to soothe a sore throat. This may give a clue to which way researchers should next advance in investigating pomegranate while looking for a mouth cancer cure.
 Near the end of our journey along the alimentary canal, dietary CLA-rich pomegranate seed oil has been found to suppress colon carcinogenesis, which inhibition is associated in part with the increased content of CLA (conjugated linoleic acid) in the colon and liver.
 


   Pomegranate general benefits:

 Moving on down the alimentary canal, traditionally anti-diarrhoeal, pomegranate rind extract has been shown to have gastro-protective activity through its antioxidant mechanism.
 Mexican researchers tested antibacterial properties of aqueous and methanolic extracts of 26 medicinal plants used in Mexico to treat gastrointestinal disorders against eight different species of entero-pathogens which cause diarrhoea and dysentery: two Escherichia coli species; two Shigella sonnei species; two Shigella flexneri species; and two Salmonella sp. species. Surprise, Surprise! Pomegranate possessed strong antibacterial activity against most of the pathogens tested. Plus, when some 54 plants extracts of importance in the Ayurvedic system of traditional Indian medicine used to treat enteric diseases were screened for their potential against multi-drug resistant Salmonella typhi, pomegranate showed strong antibacterial activity.
 Pomegranate is also one of eight plants tested by Australian researchers last year which may provide alternative but bioactive medicines for the treatment of the widespread Escherichia coli O157:H7 infection.43 Indian animal studies have also evaluated the pomegranate seed extract and established it to be effective as an anti-diarrhoeal agent.
 With regard to safe usage, in 2003 a Cuban research investigation focused on the toxicity evaluation of the whole pomegranate fruit (hydro-alcoholic) extract, which is used in traditional medicine for the treatment of respiratory diseases, because previous findings on the anti-influenza activity of pomegranate extracts had given support to the ethno-pharmacological application. It was concluded that any toxic effects of Punica granatum fruit extract occurred at higher doses than those effective in the models where the anti-viral activity has been studied or than those doses used in Cuban medicine.
 Earlier, when extracts of 13 Brazilian medicinal plants used in Brazilian folk medicine for the treatment of infectious diseases were screened for their antimicrobial activity against bacteria and yeasts, results found pomegranate showed good activity on Staphylococcus aureus bacteria and anti-candidal46A activity was detected. Also, in the early 90s, plants used in Argentine folk medicine screened for antimicrobial activity against Staphylococcus aureus, commonly present on skin and mucous membranes which causes boils and abscesses, showed that pomegranate pericarp (outer rind) extract produced one of the more active results.
 In the wake of recent world-shaking disasters, such as the Asian Tsunami , the more recent Katrina hurricane's strike on New Orleans, the September earthquake in Peru and latest large earthquake in Pakistan, the fearful spectre of 'cholera' is always waiting at the gate to claim victims. Peruvian people, in the popular treatment of diarrhoea, use natural products with good success. Accordingly, Peruvian scientists, when testing several plants in vitro on Vibrio cholerae (which causes cholera), found that tea infusion and the decoction of pomegranate peel showed the best bactericidal effect and they suggested it could be used to stop cholera spreading.
 


  Pomegranate Helps Diabetic Hearts.:SOURCES: Rosenblat, M. Atherosclerosis, August 2006; vol 186: pp 363-371. News release, American Technion Society.Jennifer Warner

 Aug. 29, 2006 -- Drinking pomegranate juice may help people with diabetes reduce their risk of heart disease.
 A preliminary new study shows that people with diabetes who drank pomegranate juice for three months had a lower risk of atherosclerosis -- or hardening of the arteries. In addition, the pomegranate juice appeared to slow the absorption of unhealthy LDL cholesterol by immune cells.
 People with diabetes have increased risk for atherosclerosis, which contributes to coronary heart disease, heart attacks, strokes, and other circulation problems.

 These results suggest that the antioxidants found in pomegranate juice may be especially beneficial in reducing these heart-related risks associated with diabetes.
 "In most juices, sugars are present in free -- and harmful -- forms," says researcher Michael Aviram, of the Technion Faculty of Medicine in Haifa, Israel, in a news release. "In pomegranate juice, however, the sugars are attached to unique antioxidants, which actually make these sugars protective against atherosclerosis."
 People with diabetes aren't able to process sugars normally and are advised to monitor their intake of food and beverages high in natural or processed sugars, including fruit juice.

 Pomegranate Juice Reduces Diabetes Risks
 In the small study, published in the journal Atherosclerosis, researchers examined the effects of drinking a specially prepared concentrated pomegranate juice that is the equivalent to about a 6-ounce glass of "single strength pomegranate juice, just as it is when you squeeze the pomegranate and get the juice," Aviram tells WebMD by email, every day for three months in 10 healthy adults and 10 adults with type 2 diabetes (who were not dependent on insulin therapy).
 Drinking pomegranate juice did not affect overall cholesterol levels, but researchers found it reduced the uptake of oxidized "bad" LDL cholesterol by immune cells, which is a major contributing factor to atherosclerosis.
 Although pomegranate juice contains a similar level of sugars as other fruit juices, Aviram says they were surprised to find that the sugars in pomegranate juice did not worsen diabetes markers, such as blood sugar levels, in the participants with diabetes.

  Pomegranate Slows Prostate Cancer.:Daniel DeNoon.SOURCES: Pantuck, A.J. Clinical Cancer Research, July 1, 2006; pp 4018-4026. News release, Jonsson Cancer Center.

 July 5, 2006 -- A glass of pomegranate juice a day may keep prostate cancer recurrence away, UCLA researchers report.

 Treatment cures two out of three men with early prostate cancer. But after treatment, a third of men have rising levels of prostate-specific antigen -- PSA -- in their blood. Of these men, 34% of them progressed to deadly, metastatic prostate cancer within 15 years. The faster PSA levels double, the sooner a man is likely to see his prostate cancer return.

 Cancer-fighting chemicals are found in many foods. One food rich in these kinds of chemicals is pomegranate juice. Might pomegranate juice slow -- or even reverse -- this post-treatment increase in PSA? Yes, find UCLA researcher Allan Pantuck, MD, and colleagues.
 Pantuck's team enrolled 46 men in a study funded by the owners of POM Wonderful Co., the maker of the pomegranate juice used in the study. The men all had detectable PSA after cancer treatment; all drank 8 ounces of pomegranate juice every day.
 The men's overall PSA doubling time was nearly four times slower after they began drinking pomegranate juice. Sixteen of the 46 patients had a decrease in PSA levels -- and in four, PSA levels dropped by half.
 "I was surprised when I saw such an improvement in PSA numbers," Pantuck said, in a news release. "This is not a cure, but we may be able to change the way prostate cancer grows."
 Pantuck says that pomegranate juice may allow 65- to 70-year-old men treated for prostate cancer to outlive their risk of dying from their cancer.

 Prostate cancer patients with rising PSA levels usually opt for treatment with drugs that block testosterone. This "chemical castration" can have serious side effects, including bone loss, depression, and sexual dysfunction. It's possible that drinking pomegranate juice can delay the need for such treatments.
 Pantuck says that some men in the study have been drinking pomegranate juice -- and keeping their PSA levels stable -- for more than three years.
 "The juice seems to be working," he notes.
 Because of these promising results, pomegranate juice will be studied in a major, placebo-controlled clinical trial at 10 U.S. medical centers.
 The study findings appear in the July 1 issue of Clinical Cancer Research

  Pomegranates May Fight Osteoarthritis.:

 SOURCES: Ahmed, S. The Journal of Nutrition, September 2005; vol 135: pp 2096-2102. National Institute of Arthritis and Musculoskeletal Diseases, "Handout on Health: Osteoarthritis." News release, Case Western Reserve University. WebMD Medical News: "Pomegranate Juice May Curb Prostate Cancer." WebMD Medical News: "Pomegranate Juice May Clear Clogged Arteries." U.S. Department of Agriculture.
 Sept. 9, 2005 -- Could osteoarthritis be brought to its knees by a simple fruit?
 Researchers aren't making that declaration just yet. But they have found signs that natural compounds called antioxidants in pomegranates may thwart osteoarthritis.
 Osteoarthritis is the most common type of arthritis, with more than 20 million patients in the U.S., according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
 The pomegranate study was done at Case Western Reserve University. The researchers included Tariq Haqqi, PhD, a professor of medicine. The results appear in The Journal of Nutrition.
 Pomegranate Project:Pomegranate extract was pitted against osteoarthritis in lab tests. That's not the same as tests on people or animals, but it's a first step.Pomegranate extract did two things in those lab tests. It cut levels of an inflammatory chemical called interleukin-1b (IL-1b). It also curbed enzymes that erode cartilage.Cartilage is a hard but slippery coating on the end of each bone that helps bones slide smoothly past each other. Osteoarthritis develops when cartilage is broken down; exposed bone breaks down, causing pain, inflammation, and disability.
 First Findings:This is the first study to show pomegranate's potential against osteoarthritis, note the researchers.The results "indicate the pomegranate fruit extract or compounds derived from it may inhibit cartilage degradation in osteoarthritis and may also be a useful nutritive supplement for maintaining joint integrity and function," they write.
 Researcher's Comments:"Arthritis is one of the foremost diseases for which patients seek herbal or traditional medicine treatments," says Haqqi in a news release."However, all the extracts and herbs have not been scientifically evaluated for their efficacy and safety. Indeed, some of them may even interfere with current treatments," he continues."Therefore, careful use of supplements and herbal medicines during early stages of disease or treatment may be made to limit the disease progression," says Haqqi.As always, discuss any supplement use with your doctor.
 Pomegranate Potion:The researchers didn't just crack open a pomegranate and put it in a blender. They also didn't use juice from the supermarket.Instead, they made their own pomegranate extract from powdered pomegranate. Sophisticated filtering and measuring was used for science's sake.The pomegranate has "been revered through the ages for its medicinal uses," write the researchers.Antioxidants in pomegranates fight inflammation and may also counter cancer and heart disease.In May, researchers reported that pomegranate juice may help prevent the return of prostate cancer. In March, another study showed that pomegranate juice may fight hardening of the arteries.
 Pomegranate Season:Pomegranates are in season in the U.S. in the fall. They've got a thick, red, leathery skin. The seeds inside are the edible part.Want to try a pomegranate? You might want to wear a bib or old clothes. The seeds leave a very strong stain and are used as a dye.

  Pomegranates May Prevent Prostate Cancer.:

 Sept. 27, 2005 -- A pomegranate a day may keep prostate cancer away, according to early results that suggest the antioxidant-rich fruit may both prevent and treat the deadly cancer.
 Researchers found pomegranate juice killed human prostate cancer cells in laboratory tests and significantly slowed the progression of prostate cancer in mice.
 "Our study -- while early -- adds to growing evidence that pomegranates contain very powerful agents against cancer, particularly prostate cancer," researcher Hasan Mukhtar, PhD, professor of dermatology at the University of Wisconsin Medical School, says in a news release.
 "There is good reason now to test this fruit in humans -- both for cancer prevention and for treatment."

 Breaking New Ground:Prostate cancer is the second-leading cause of cancer death in American men, behind lung cancer.
 Researchers say the study, published in the Proceedings of the National Academy of Sciences, is the first to evaluate the effects of pomegranate extract on human prostate cancer cells.
 Previous studies have shown that the ruby-seeded fruit native to the Middle East is rich in antioxidants and has anti-inflammatory effects. In fact, researchers say pomegranate juice has higher levels of antioxidants than red wine and green tea, which have also been investigated as potential cancer treatments.

 More Pomegranates, Less Cancer?

 In this study, researchers examined whether pomegranate juice would not only kill cancer but also help prevent prostate cancer from starting or progressing.
 In the first experiment, researchers treated human prostate cancer cells with various doses of pomegranate juice in the laboratory. The results showed that the higher the pomegranate dose, the more prostate cancer cells that were killed.
 In the second test, researchers divided mice injected with human prostate cancer cells into three groups. One group drank water and the other two groups drank either 0.1% pomegranate extract or 0.2% pomegranate extract.
 Researchers say the dose of pomegranate juice given to the mice equates to about one or two pomegranates -- or 8 to 16 ounces of pomegranate juice.
 The results showed that mice who drank the higher concentration of pomegranate extract experienced a significant slowing in their cancer progression and a decrease in prostate-specific antigen (PSA) levels. PSA is used to indicate the presence of prostate problems, including cancer, in humans.
 Now, researchers say the next step in evaluating pomegranates as a potential prostate cancer treatment is to conduct studies in humans.

  Two Natural Prostate Therapies Strike Out.:Neil Osterweil.AUA 2005 Annual Meeting: Abstracts 831, 1014, 1637. Presented May 22, 2005.

 May 24, 2005 (San Antonio) ¡ª Tons of tomatoes and fields of saw palmetto plants may have perished in vain, suggest authors of two studies presented here at the American Urological Association's 2005 Annual Meeting.
 Lycopene, found in tomatoes and other fruits and vegetables, does not appear to decrease the risk of prostate cancer, and saw palmetto was no better than placebo in a randomized controlled trial for treatment of benign prostatic hyperplasia (BPH).
 But, a third study found that men with rising prostate-specific antigen (PSA) levels after definitive prostate cancer therapy who drink 8 oz daily of pomegranate juice had significantly longer PSA doubling times.
 "The positive and significant beneficial effects on PSA parameters achieved, coupled with corresponding laboratory effects on prostate cancer in vitro cell growth and apoptosis warrant further testing," said lead investigator Allan Pantuck, MD, assistant professor of Urology at the University of California, Los Angeles.

 Dr. Pantuck and colleagues conducted a two-year, single center, two-stage, clinical trial in men who had rising PSA levels despite having undergone radical prostatectomy or radiation therapy. To be eligible, patients had to have a PSA level between 0.2 and 5.0 ng/mL, and a Gleason score of 7 or less. They were tested with serial PSA measurements, which were used to determine PSA doubling time.
 The participants drank 8 oz daily of the juice of pomegranates, which they selected on the advice of a panel of nutritional experts. The juice contains antioxidant polyphenols equivalent to 1.5 mmol per day.
 Clinical endpoints included safety, effect on serum PSA levels, and exploratory laboratory studies. The investigators found that at the end of the study about 71% of the patients had stable disease, 31% experienced a drop in PSA levels, ranging from 5% to 85% over baseline. In addition, 82.5% of patients had lengthening of their PSA doubling times, indicating a slowing of disease progression. The average PSA doubling time went from 15 months at baseline to 37 months at study end.

 Dr. Pantuck suggested that the slowing of the PSA doubling time might signal a delayed time to metastases that could last for several years, during which time many patients may die from other causes.
 Dr. Pantuck noted that in vitro tests of serum also showed reduced proliferation and increased apoptosis of prostate cancer cells. The researchers are planning a phase 3 multicenter study.

 In the saw palmetto trial, Andrew Avins, MD, assistant professor of medicine and epidemiology at the University of California, San Francisco, and colleagues tested the theory that saw palmetto extract can improve urinary flow in men with BPH. At total of 225 men aged 50 years and older were enrolled in a randomized, placebo-controlled trial. All men had American Urological Association Symptom Inventory (AUASI) scores between 8 and 35, and all had a diagnosis of BPH. They were randomly assigned to receive 160 mg of saw palmetto twice a day or a matching-placebo capsule. Patients were seen eight times for one year for assessment of AUASI changes, maximal urine flow, post-void residual urine volume, prostate size, and other health-related outcomes.
 "In contrast to most prior studies, we found no significant benefit of saw palmetto on urinary symptoms or objective measures of benign prostatic hyperplasia for a one-year period," Dr. Avins said in a media briefing.

 In the lycopene study, Peter Clark, MD, assistant professor of urology at Wake Forest University, Winston-Salem, North Carolina, and colleagues enrolled 36 men with recurrent prostate cancer in a dose-escalation trial. The study was designed to see whether lycopene could retard or prevent the development of prostate cancer. It was prompted by the anecdotal finding of a substantial reduction in PSA level and in residual cancer in a patient who had taken a saw palmetto and lycopene combination.

 At the time of enrollment, each participant was assigned to lycopene supplement dose ranging from 15 to 120 mg a day for 12 months.

 At one year, however, none of the 35 patients available for follow-up showed any benefit from lycopene. The mean PSA doubling time at baseline was 3.7 years, and at study end was 4.1 years; this difference was not statistically significant. In addition, PSA slope, which indicated the change in PSA level for a sustained period, was 0.010 before lycopene administration and 0.011 at study end; this difference was also not significant.

 Asked by Medscape whether a synergistic effect of saw palmetto and lycopene might have accounted for the results they saw in the patient whose case prompted the study, Dr. Clark said, "We have thought long and hard about it…The problem basically is whether anybody is going to sink money into a trial to look at that based on one patient, and that is where you run into problems."
 Dr. Clark said that in vitro studies using combinations in cell lines may be necessary to tease out effects of particular agents.

 One of the problems with alternative therapies, says Isaac Powell, MD, professor of urology at Wayne State University's Karamanos Cancer Center in Detroit, Michigan, is that there is a lack of standardization, and these agents often do not undergo the rigorous scrutiny that conventional pharmaceuticals are subjected to.
 "I have patients who have chosen to use [alternative medicine] and 'that is their choice. They still have cancer, we biopsy them, and they still have cancer. It has not grown very rapidly, but would it have grown rapidly otherwise? You would have to have a comparative or randomized study to answer that question," said Dr. Powell in an interview with Medscape seeking objective commentary.

 Dr. Avins's study was funded by the National Institutes of Health's National Institute on Complementary and Alternative Medicine. Dr. Pantuck's study was funded by POM Wonderful, a maker of pomegranate juice. Dr. Clark's study was internally funded.
 None of the investigators disclosed any pertinent financial information.


  Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells.:

 J Ethnopharmacol. 2006; 103(3):311-8 (ISSN: 0378-8741).Aslam MN; Lansky EP; Varani J.Department of Pathology, The University of Michigan Medical School, 1301 Catherine Road/Box 0602, Ann Arbor, MI 48109, USA.
 Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit's peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.

  Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells.:

 J Agric Food Chem. 2006; 54(3):980-5 (ISSN: 0021-8561).Adams LS; Seeram NP; Aggarwal BB; Takada Y; Sand D; Heber D.Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. ladams@mednet.ucla.edu
 Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.

  Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.:

 Clin Cancer Res. 2006; 12(13):4018-26 (ISSN: 1078-0432).Pantuck AJ; Leppert JT; Zomorodian N; Aronson W; Hong J; Barnard RJ; Seeram N; Liker H; Wang H; Elashoff R; Heber D; Aviram M; Ignarro L; Belldegrun A.Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1738, USA. apantuck@mednet.ucla.edu
 PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy. EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels. RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption. CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.

  Anticancer activities of pomegranate extracts and genistein in human breast cancer cells.:

 J Med Food. 2005; 8(4):469-75 (ISSN: 1096-620X).Jeune MA; Kumi-Diaka J; Brown J.Department of Biological Sciences, Charles E. Schmidt College of Science, Florida Atlantic University, Davie, FL 33314-7714, USA. celestre@iwon.com
 Previous studies have demonstrated the anticarcinogenic activity of pomegranate extracts and genistein in a series of human cancer cells. In the present study, the potential anticancer effects of pomegranate extracts and genistein on inhibition of cell proliferation and induction of apoptosis in human breast cancer cells was investigated. Human breast cancer cells (MCF-7) were cultured as monolayers in complete RPMI 1640 medium. The cells were cultured for 48 hours to allow growth and achieve about 80% confluence in 48-well culture plates, and then exposed to the agents for 24 hours in single and combination treatments. Post-treatment growth rate and apoptosis induction were assessed by the use of a series of bioassays-lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (inner salt) for viability and cytotoxicity; acridine orange-ethidium bromide and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays for induction of apoptosis. Both pomegranate extracts and genistein had significant (dose- and time-dependent) cytotoxic and growth inhibition effects on MCF-7 cancer cells. Both growth inhibition and cytotoxicity were significantly higher (P < .01) in the combination treatments than in the single treatments with either agent. The data revealed that both drugs in single and in combination treatments induced apoptosis in MCF-7 cells. Apoptotic induction in the combination treatments was significantly higher (P < .01) than in single treatments. Both pomegranate extracts and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis, with combination treatment being more efficacious than single treatments.

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  Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease.:

 Am J Cardiol. 2005; 96(6):810-4 (ISSN: 0002-9149).Sumner MD; Elliott-Eller M; Weidner G; Daubenmier JJ; Chew MH; Marlin R; Raisin CJ; Ornish D.The Preventive Medicine Research Institute, Sausalito, California, USA.
 Pomegranate juice contains antioxidants such as soluble polyphenols, tannins, and anthocyanins and may have antiatherosclerotic properties. However, no study has investigated the effects of pomegranate juice on patients who have ischemic coronary heart disease (CHD). We investigated whether daily consumption of pomegranate juice for 3 months would affect myocardial perfusion in 45 patients who had CHD and myocardial ischemia in a randomized, placebo-controlled, double-blind study. Patients were randomly assigned into 1 of 2 groups: a pomegranate juice group (240 ml/day) or a placebo group that drank a beverage of similar caloric content, amount, flavor, and color. Participants underwent electrocardiographic-gated myocardial perfusion single-photon emission computed tomographic technetium-99m tetrofosmin scintigraphy at rest and during stress at baseline and 3 months. Visual scoring of images using standardized segmentation and nomenclature (17 segments, scale 0 to 4) was performed by a blinded independent nuclear cardiologist. To assess the amount of inducible ischemia, the summed difference score (SDS) was calculated by subtracting the summed score at rest from the summed stress score. The experimental and control groups showed similar levels of stress-induced ischemia (SDS) at baseline (p >0.05). After 3 months, the extent of stress-induced ischemia decreased in the pomegranate group (SDS -0.8 +/- 2.7) but increased in the control group (SDS 1.2 +/- 3.1, p <0.05). This benefit was observed without changes in cardiac medications, blood sugar, hemoglobin A1c, weight, or blood pressure in either group. In conclusion, daily consumption of pomegranate juice may improve stress-induced myocardial ischemia in patients who have CHD.

  Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice.:

 Food Chem Toxicol. 2006; 44(7):984-93 (ISSN: 0278-6915).Kaur G; Jabbar Z; Athar M; Alam MS.Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
 Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study evaluated antioxidant and hepatoprotective activity of pomegranate flowers. Alcoholic (ethanolic) extract of flowers was prepared and used in the present study. The extract was found to contain a large amount of polyphenols and exhibit enormous reducing ability, both indicative of potent antioxidant ability. The extract showed 81.6% antioxidant activity in DPPH model system. The ability of extract to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) was tested and it was found to significantly scavenge superoxide (O(2)(.-)) (by up to 53.3%), hydrogen peroxide (H(2)O(2)) (by up to 30%), hydroxyl radicals (()OH) (by up to 37%) and nitric oxide (NO) (by up to 74.5%). The extract also inhibited (.)OH induced oxidation of lipids and proteins in vitro. These results indicated pomegranate flower extract to exert a significant antioxidant activity in vitro. The efficacy of extract was tested in vivo and it was found to exhibit a potent protective activity in acute oxidative tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Intraperitoneal administration of 9 mg/kg body wt. Fe-NTA to mice induced oxidative stress and liver injury. Pretreatment with pomegranate flower extract at a dose regimen of 50-150 mg/kg body wt. for a week significantly and dose dependently protected against Fe-NTA induced oxidative stress as well as hepatic injury. The extract afforded up to 60% protection against hepatic lipid peroxidation and preserved glutathione (GSH) levels and activities of antioxidant enzymes viz., catalase (CAT), glutathione peroxidase (GPX) glutathione reductase (GR) and glutathione-S-transferase (GST) by up to 36%, 28.5%, 28.7%, 40.2% and 42.5% respectively. A protection against Fe-NTA induced liver injury was apparent as inhibition in the modulation of liver markers viz., aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and albumin in serum. The histopathological changes produced by Fe-NTA, such as ballooning degeneration, fatty changes, necrosis were also alleviated by the extract. These results indicate pomegranate flowers to possess potent antioxidant and hepatoprotective property, the former being probably responsible for the latter.

  In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice.:

 J Nutr Biochem. 2005; 16(6):360-7 (ISSN: 0955-2863).Seeram NP; Adams LS; Henning SM; Niu Y; Zhang Y; Nair MG; Heber D.Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. nseeram@mednet.ucla.edu
 Pomegranate (Punica granatum L.) fruits are widely consumed as juice (PJ). The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA). Punicalagin is the major antioxidant polyphenol ingredient in PJ. Punicalagin, EA, a standardized total pomegranate tannin (TPT) extract and PJ were evaluated for in vitro antiproliferative, apoptotic and antioxidant activities. Punicalagin, EA and TPT were evaluated for antiproliferative activity at 12.5-100 microg/ml on human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, 22Rv1) tumor cells. Punicalagin, EA and TPT were evaluated at 100 microg/ml concentrations for apoptotic effects and at 10 microg/ml concentrations for antioxidant properties. However, to evaluate the synergistic and/or additive contributions from other PJ phytochemicals, PJ was tested at concentrations normalized to deliver equivalent amounts of punicalagin (w/w). Apoptotic effects were evaluated against the HT-29 and HCT116 colon cancer cell lines. Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 microg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.

  Analysis of fenhexamid in caneberry, blueberry, and pomegranate by liquid chromatography-tandem mass spectrometry.:

 J Agric Food Chem. 2003; 51(23):6635-9 (ISSN: 0021-8561).Hengel M; Hung B; Engebretson J; Shibamoto T.Department of Environmental Toxicology, University of California at Davis, One Shields Avenue, Davis, California 95616, USA. mjhengel@ucdavis.edu
 An analytical method for the determination of fenhexamid [N-(2,3-dichloro-4-hydroxyphenyl)-1-methylcyclohexanecarboxamide] in caneberry, blueberry, and pomegranate was developed utilizing acetone extraction, column cleanup, liquid-liquid partitioning, and liquid chromatography-tandem mass spectroscopy (LC-MS/MS) for detection. Method validation recoveries ranged from 91 to 96% for caneberry, from 80 to 91% for blueberry, and from 74 to 95% for pomegranate. Control samples collected from IR-4 trials for all matrixes had residue levels of <0.020 ppm. Fenhexamid-treated field samples had residue levels that ranged from 0.46 to 16.11 ppm (caneberry), from 0.87 to 2.91 ppm (blueberry), and from 1.59 to 1.85 ppm (pomegranate). The method was validated to a limit of quantitation of 0.020 ppm, and the limit of detection was 0.009 ppm.

  Pomegranate extract inhibits Staphylococcus aureus growth and subsequent enterotoxin production.:

 J Ethnopharmacol. 2005; 96(1-2):335-9 (ISSN: 0378-8741).Braga LC; Shupp JW; Cummings C; Jett M; Takahashi JA; Carmo LS; Chartone-Souza E; Nascimento AM.Departamento de Biologia Geral, Instituto de Ci??ncias Biol??gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
 In Brazil, pomegranate (Punica granatum L. (Punicaceae)) is widely used as a phytotherapeutic agent. This study evaluates the effect of pomegranate extract on Staphylococcus aureus FRI 722 growth and subsequent enterotoxin production. Bacterial susceptibility was determined by tube dilution method and production of enterotoxin was assessed using membrane-over-agar (MOA) plates. At a low extract concentration (0.01% v/v) bacterial growth was delayed, while a higher concentration (1% v/v) eliminated bacterial growth. Most interestingly, a 0.05% (v/v) concentration of extract was found to inhibit Staphylococcal enterotoxin (SE) A production. These data further implicate pomegranate extracts as potential antibacterial therapeutics with the added ability to inhibit enterotoxin production.


  Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers.:

 J Agric Food Chem. 2006; 54(23):8956-61 (ISSN: 0021-8561).Mertens-Talcott SU; Jilma-Stohlawetz P; Rios J; Hingorani L; Derendorf H.Pharmaceutics Department, University of Florida, Gainesville, Florida 32610, USA. smertens@ufl.edu
 The intake of polyphenols has been demonstrated to have health-promoting and disease-preventive effects. The pomegranate (Punica granatum L.), which is rich in several polyphenols, has been used for centuries in ancient cultures for its medicinal purposes. The potential health benefits of pomegranate polyphenols have been demonstrated in numerous in vitro studies and in vivo experiments. This study investigated the absorption and antioxidant effects of a standardized extract from pomegranate in healthy human volunteers after the acute consumption of 800 mg of extract. Results indicate that ellagic acid (EA) from the extract is bioavailable, with an observed C(max) of 33 ng/mL at t(max) of 1 h. The plasma metabolites urolithin A, urolithin B, hydroxyl-urolithin A, urolithin A-glucuronide, and dimethyl ellagic acid-glucuronide were identified by HPLC-MS. The antioxidant capacity measured with the oxygen radical absorbance capacity (ORAC) assay was increased with a maximum effect of 32% after 0.5 h, whereas the generation of reactive oxygen species (ROS) was not affected. The inflammation marker interleukin-6 (IL-6) was not significantly affected after 4 h after the consumption of the extract. Overall, this study demonstrated the absorbability of EA from a pomegranate extract high in ellagitannin content and its ex vivo antioxidant effects.

  Beware of pomegranates bearing 40% ellagic Acid.:

 J Med Food. 2006; 9(1):119-22 (ISSN: 1096-620X).Lansky EP.Rimonest Ltd., Haifa, Israel. info@rimonest.com
 A recent profusion of pomegranate nutraceutical products, "standardized to 40% ellagic acid," has appeared in the marketplace. This Perspective reviews the chemical and functional studies of pomegranate as well as the virtues and dangers of ellagic acid, and concludes that synergy among the various pomegranate fractions and phytochemicals is the most important factor for assessing strength of pomegranate nutraceutical preparations, and not simply the concentration of ellagic acid. Ellagic acid concentration in final products is likely to have an optimal therapeutic range, which very likely is less than 40%. The wisdom of designing and engineering pomegranate nutraceutical products to maximize therapeutic or chemopreventive synergy is suggested, as opposed to preparations that are designed and engineered simply to maximize the concentration of a single phytochemical. The implications of this strategy may be generalized for the optimization of nutraceutical preparations from other medicinal plants as well.

  Pharmacokinetic study of ellagic acid in rat after oral administration of pomegranate leaf extract.:

 J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 796(1):189-94 (ISSN: 1570-0232).Lei F; Xing DM; Xiang L; Zhao YN; Wang W; Zhang LJ; Du LJ.Institute of Medicinal Plant, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100094, China.
 Quantification of ellagic acid, the principal bioactive component of pomegranate leaf extract, in rats plasma following oral administration of pomegranate leaf extract was achieved by using a high-performance liquid chromatographic method. The calibration curve for ellagic acid was linear (r2=0.9998) ver the concentration range 0.026-1.3 microg/ml. The intra- and inter-day assays of ellagic acid from rat plasma were less than 6.52% at concentration range from 26 to 1300 ng/ml and good overall recoveries (94.5-102.4%) were found on same concentrations. The concentration-time profile was fitted with an open two-compartment system with lag time and its max concentration of ellagic acid in plasma was 213 ng/ml only 0.55 h after oral administration extract 0.8 g/kg. The pharmacokinetic profile indicates that ellagic acid has poor absorption and rapid elimination after oral administration pomegranate leaf extract, and part of it was absorbed from stomach.

  Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic.:

 J Agric Food Chem. 2003; 51(11):3493-501 (ISSN: 0021-8561).Cerd?? B; Cer??n JJ; Tom??s-Barber??n FA; Esp??n JC.Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 4195, 30080 Murcia, Spain.
 The water-soluble ellagitanin punicalagin has been reported to be toxic to cattle. Taking into account that this antioxidant polyphenol is very abundant in pomegranate juice (> or =2 g/L), the present study evaluated the possible toxic effect of punicalagin in Sprague-Dawley rats upon repeated oral administration of a 6% punicalagin-containing diet for 37 days. Punicalagin and related metabolites were identified by HPLC-DAD-MS-MS in plasma, liver, and kidney. Five punicalagin-related metabolites were detected in liver and kidney, that is, two ellagic acid derivatives, gallagic acid, 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one glucuronide, and 3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one. Feedstuff intake, food utility index, and growth rate were lower in treated rats during the first 15 days without significant adverse effects, which could be due to the lower nutritional value of the punicalagin-enriched diet together with a decrease in its palatability (lower food intake). No significant differences were found in treated rats in any blood parameter analyzed (including the antioxidant enzymes gluthatione peroxidase and superoxide dismutase) with the exception of urea and triglycerides, which remained at low values throughout the experiment. Although the reason for the decrease is unclear, it could be due to the lower nutritional value of the punicalagin-enriched diet with respect to the standard rat food. Histopathological analysis of liver and kidney corroborated the absence of toxicity. In principle, the results reported here, together with the large safety margin considered, indicate the lack of toxic effect of punicalagin in rats during the 37 day period investigated. However, taking into account the high punicalagin content of pomegranate-derived foodstuffs, safety evaluation should be also carried out in humans with a lower dose and during a longer period of intake.

  Study on the qualitative and quantitative methods of gallic acid in pomegranate rind.:

 Zhongguo Zhong Yao Za Zhi. 2005; 30(15):1171-2 (ISSN: 1001-5302).Wang KY.Guizhou Institute for Drug Control, Guiyang 550004, China.
 OBJECTIVE: To establish the qualitative and quantitative methods of gallic acid in pomegranate rind. METHOD: The thin layer chromatographic method was used for identitication, and the high performance liquid chromatographic method was used for assay. Extracts were separated on a Diamonsil C18 column eluted with the mobile phase of a mixture of acetonitrile containing 0.2% methanol and water containing 0.1% phosphoric acid and 0.1% TEA (3:97). The detection wavelength was set at 216 nm, and colum temperature was 40 degrees C. RESULT: The calibration curve was linear in the range of 0.085-0.768 microg (r = 0.9996). The average recovery was 96.7% (RSD 0.8%, n = 5). 20 batches of the crude drug were identified and assayed, with the methods. CONCLUSION: The methods were sensitive and reliable, and can be used for quality control of the pomegranate rind.


  Polyphenols from green tea and pomegranate for prevention of prostate cancer.:

 Free Radic Res. 2006; 40(10):1095-104 (ISSN: 1071-5762).Adhami VM; Mukhtar H.Department of Dermatology, University of Wisconsin-Madison, Madison, WI 53706, USA.
 Prostate cancer (PCa) is the most common non-cutaneous cancer diagnosed in North America with similar trends in many Western countries. Geographic, epidemiological and laboratory studies suggest a role for dietary constituents in the etiology as well as prevention of PCa. The rising incidence of PCa in several countries appears to be coincidental with adoption of western lifestyle. Increase in the incidence of PCa has also been found in Asian populations migrating to the west. These facts give numerous leads to explore testable PCa prevention strategies. There is growing evidence in support of use of dietary ingredients in prevention and treatment of PCa. While substantial data exists in favor of use of polyphenols from tea as PCa chemopreventive agent, interest in anti-cancer properties of polyphenols from pomegranate has recently emerged. This review summarizes current literature on the effects of polyphenols from green tea and pomegranate against PCa.

  beta-Secretase (BACE1) inhibitors from pomegranate (Punica granatum) husk.:

 Arch Pharm Res. 2005; 28(12):1328-32 (ISSN: 0253-6269).Kwak HM; Jeon SY; Sohng BH; Kim JG; Lee JM; Lee KB; Jeong HH; Hur JM; Kang YH; Song KS.School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, Korea.
 In the course of screening for anti-dementia agents from natural products, two beta-secretase (BACE1) inhibitors were isolated from the husk of pomegranate (Punica granatum) by activity-guided purification. They were identified as ellagic acid and punicalagin with IC50 values of 3.9 x10(-6) and 4.1x10(-7) M and Ki values of 2.4x10(-5) and 5.9x10(-7) M, respectively. The compounds were non-competitive inhibitors with a substrate in the Dixon plot. Ellagic acid and punicalagin were less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, thus indicating that they were relatively specific inhibitors of BACE1.

  Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide.:

 Nitric Oxide. 2006; 15(2):93-102 (ISSN: 1089-8603)Ignarro LJ; Byrns RE; Sumi D; de Nigris F; Napoli C.Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. lignarro@mednet.ucla.edu
 Pomegranate juice (PJ), which is a rich source of potent flavonoid antioxidants, was tested for its capacity to protect nitric oxide (NO) against oxidative destruction and enhance the biological actions of NO. Employing chemiluminescence headspace analysis, PJ was found to be a potent inhibitor of superoxide anion-mediated disappearance of NO. PJ was much more potent than Concord grape juice, blueberry juice, red wine, ascorbic acid, and DL-alpha-tocopherol. As little as 3 microl of a 6-fold dilution of PJ, in a reaction volume of 5000 microl, produced a marked antioxidant effect, whereas 300 microl of undiluted blueberry juice or nearly 1000 microl of undiluted Concord grape juice were required to produce similar effects. PJ and other antioxidant-containing products were found to augment the anti-proliferative action of NO (DETA/NO) on vascular smooth muscle cell (rat aorta) proliferation. PJ was much more effective than the other products tested and elicited no effects when tested alone in the absence of added NO. Similarly, neither PJ nor the other products enhanced the anti-proliferative action of alpha-difluoromethylornithine, a stable substance that inhibits cell growth by NO-independent mechanisms. In order to determine whether PJ is capable of increasing the production of NO by vascular endothelial cells, PJ was tested for its capacity to upregulate and/or activate endothelial NO synthase (eNOS) in bovine pulmonary artery endothelial cells. PJ elicited no effects on eNOS protein expression or catalytic activity. Moreover, PJ did not enhance promoter activity in the eNOS gene (COS-7 cells transfected with eNOS). These observations indicate that PJ possesses potent antioxidant activity that results in marked protection of NO against oxidative destruction, thereby resulting in augmentation of the biological actions of NO.

  Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats.:

 Cancer Sci. 2004; 95(6):481-6 (ISSN: 1347-9032)
 Pomegranate (Punica granatum L.) seed oil (PGO) contains more than 70% cis(c)9,trans(t)11,c13-18:3 as conjugated linolenic acids (CLN). Our previous short-term experiment demonstrated that seed oil from bitter melon (Momordica charantia) (BMO), which is rich in c9,t11,t13-CLN, inhibited the occurrence of colonic aberrant crypt foci (ACF) induced by azoxymethane (AOM). In this study, we investigated the effect of dietary PGO on the development of AOM-induced colonic malignancies and compared it with that of conjugated linoleic acid (CLA). To induce colonic tumors, 6-week old male F344 rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks. One week before the AOM treatment they were started on diet containing 0.01%, 0.1%, or 1% PGO or 1% CLA for 32 weeks. Upon termination of the bioassay (32 weeks) colon tumors were evaluated histopathologically. AOM exposure produced colonic adenocarcinoma with an incidence of 81% and multiplicity of 1.88 +/- 1.54 at week 32. Administration of PGO in the diet significantly inhibited the incidence (AOM + 0.01% PGO, 44%, P < 0.05; AOM + 0.1% PGO, 38%, P < 0.01; AOM + 1% PGO, 56%) and the multiplicity (AOM + 0.01% PGO, 0.56 +/- 0.73, P < 0.01; AOM + 0.1% PGO, 0.50 +/- 0.73, P < 0.005; AOM + 1% PGO, 0.88 +/- 0.96, P < 0.05) of colonic adenocarcinomas, although a clear dose-response relationship was not observed at these dose levels. CLA feeding also slightly, but not significantly, reduced the incidence and multiplicity of colonic adenocarcinomas. The inhibition of colonic tumors by PGO was associated with an increased content of CLA (c9,t11-18:2) in the lipid fraction of colonic mucosa and liver. Also, administration of PGO in the diet elevated expression of peroxisome proliferator-activated receptor (PPAR) gamma protein in the non-tumor mucosa. These results suggest that PGO rich in c9,t11,c13-CLN can suppress AOM-induced colon carcinogenesis, and the inhibition is associated in part with the increased content of CLA in the colon and liver and/or increased expression of PPARgamma protein in the colon mucosa.

  Bioactive compounds from the seeds of Punica granatum (pomegranate).:

 J Nat Prod. 2004; 67(12):2096-8 (ISSN: 0163-3864).Wang RF; Xie WD; Zhang Z; Xing DM; Ding Y; Wang W; Ma C; Du LJ.Laboratory of Pharmaceutical Sciences, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
 Two new compounds, coniferyl 9-O-[beta-D-apiofuranosyl(1-->6)]-O-beta-D-glucopyranoside (1) and sinapyl 9-O-[beta-d-apiofuranosyl(1-->6)]-O-beta-D-glucopyranoside (2), were isolated from the seeds of Punica granatum (pomegranate), together with five known compounds, 3,3'-di-O-methylellagic acid (3), 3,3',4'-tri-O-methylellagic acid (4), phenethyl rutinoside, icariside D1, and daucosterol. The structures of 1 and 2 were elucidated by spectroscopic data analysis. Compounds 1-4 exhibited antioxidant activity, which was evaluated by measurement of low-density lipoprotein (LDL) susceptibility to oxidation and by determination in vitro of malondialdehyde (MDA) levels in the rat brain.


  Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation.:

 Biosci Biotechnol Biochem. 2005; 69(12):2368-73 (ISSN: 0916-8451).
 A pomegranate extract (PE) from the rind containing 90% ellagic acid was tested for its skin-whitening effect. PE showed inhibitory activity against mushroom tyrosinase in vitro, and the inhibition by the extract was comparable to that of arbutin, which is a known whitening agent. PE, when administered orally, also inhibited UV-induced skin pigmentation on the back of brownish guinea pigs. The intensity of the skin-whitening effect was similar between guinea pigs fed with PE and those fed with L-ascorbic acid. PE reduced the number of DOPA-positive melanocytes in the epidermis of UV-irradiated guinea pigs, but L-ascorbic acid did not. These results suggest that the skin-whitening effect of PE was probably due to inhibition of the proliferation of melanocytes and melanin synthesis by tyrosinase in melanocytes. PE, when taken orally, may be used as an effective whitening agent for the skin.

  Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus.:

 Can J Microbiol. 2005; 51(7):541-7 (ISSN: 0008-4166).Braga LC; Leite AA; Xavier KG; Takahashi JA; Bemquerer MP; Chartone-Souza E; Nascimento AM.Departamento de Biologia Geral, Instituto de Ci??ncias Biol??gicas, Universidade Federal de Minas Gerais, Brazil.
 We evaluated the interaction between Punica granatum (pomegranate) methanolic extract (PGME) and antibiotics against 30 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Susceptibility testing of the isolates to PGME and antibiotics was performed by the broth dilution method. Synergic activity was detected between PGME and the 5 antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to 73%. For some isolates, PGME did not interfere with the action of any of the antibiotics tested. The bactericidal activity of PGME (0.1 x MIC) in combination with ampicillin (0.5 x MIC) was assessed using chosen isolates by time-kill assays, and they confirmed the synergic activity. Using this combination, cell viability was reduced by 99.9% and 72.5% in MSSA and MRSA populations, respectively. PGME increased the post-antibiotic effect (PAE) of ampicillin from 3 to 7 h. In addition, PGME demonstrated the potential to either inhibit the efflux pump NorA or to enhance the influx of the drug. The detection of in vitro variant colonies of S. aureus resistant to PGME was low and they did not survive. In conclusion, PGME dramatically enhanced the activity of all antibiotics tested, and thus, offers an alternative for the extension of the useful lifetime of these antibiotics.

  Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation.:

 Clin Nutr. 2004; 23(3):423-33 (ISSN: 0261-5614).Aviram M; Rosenblat M; Gaitini D; Nitecki S; Hoffman A; Dornfeld L; Volkova N; Presser D; Attias J; Liker H; Hayek T.The Lipid Research Laboratory, Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, Israel. aviram@tx.technion.ac.il
 Dietary supplementation with polyphenolic antioxidants to animals was shown to be associated with inhibition of LDL oxidation and macrophage foam cell formation, and attenuation of atherosclerosis development. We investigated the effects of pomegranate juice (PJ, which contains potent tannins and anthocyanins) consumption by atherosclerotic patients with carotid artery stenosis (CAS) on the progression of carotid lesions and changes in oxidative stress and blood pressure. Ten patients were supplemented with PJ for 1 year and five of them continued for up to 3 years. Blood samples were collected before treatment and during PJ consumption. In the control group that did not consume PJ, common carotid intima-media thickness (IMT) increased by 9% during 1 year, whereas, PJ consumption resulted in a significant IMT reduction, by up to 30%, after 1 year. The patients' serum paraoxonase 1 (PON 1) activity was increased by 83%, whereas serum LDL basal oxidative state and LDL susceptibility to copper ion-induced oxidation were both significantly reduced, by 90% and 59%, respectively, after 12 months of PJ consumption, compared to values obtained before PJ consumption. Furthermore, serum levels of antibodies against oxidized LDL were decreased by 19%, and in parallel serum total antioxidant status (TAS) was increased by 130% after 1 year of PJ consumption. Systolic blood pressure was reduced after 1 year of PJ consumption by 21% and was not further reduced along 3 years of PJ consumption. For all studied parameters, the maximal effects were observed after 1 year of PJ consumption. Further consumption of PJ, for up to 3 years, had no additional beneficial effects on IMT and serum PON1 activity, whereas serum lipid peroxidation was further reduced by up to 16% after 3 years of PJ consumption. The results of the present study thus suggest that PJ consumption by patients with CAS decreases carotid IMT and systolic blood pressure and these effects could be related to the potent antioxidant characteristics of PJ polyphenols.

  Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models.:

 J Agric Food Chem. 2002; 50(17):4791-5 (ISSN: 0021-8561).Chidambara Murthy KN; Jayaprakasha GK; Singh RP.Government College of Pharmacy, Bangalore 560 027, India.
 Pomegranate (Punica granatum) peel extracts have been shown to possess significant antioxidant activity in various in vitro models. Dried pomegranate peels were powdered and extracted with methanol for 4 h. The dried methanolic extract was fed to albino rats of the Wistar strain, followed by carbon tetrachloride (CCl4), and the levels of various enzymes, such as catalase, peroxidase, and superoxide dismutase (SOD), and lipid peroxidation were studied. Treatment of rats with a single dose of CCl4 at 2.0 g/kg of body weight decreases the levels of catalase, SOD, and peroxidase by 81, 49, and 89% respectively, whereas the lipid peroxidation value increased nearly 3-fold. Pretreatment of the rats with a methanolic extract of pomegranate peel at 50 mg/kg (in terms of catechin equivalents) followed by CCl4 treatment causes preservation of catalase, peroxidase, and SOD to values comparable with control values, wheres lipid peroxidation was brought back by 54% as compared to control. Histopathological studies of the liver were also carried out to determine the hepatoprotection effect exhibited by the pomegranate peel extract against the toxic effects of CCl4. Histopathological studies of the liver of different groups also support the protective effects exhibited by the MeOH extract of pomegranate peel by restoring the normal hepatic architecture.

  Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin.:

 J Agric Food Chem. 2002; 50(1):166-71 (ISSN: 0021-8561)
 Antioxidant activities of freeze-dried preparations of a 70% acetone extract of pomegranate (Punica granatum L.) and its three major anthocyanidins (delphinidin, cyanidin, and pelargonidin) were evaluated. Free radical scavenging activities were examined using an ESR technique with spin trapping; DMPO for hydroxyl (.OH) and superoxide (O(2)(.-) ) radicals; and [(MGD)(2)Fe(2+)] for nitric oxide (NO). Inhibitory effects on lipid peroxidation were estimated by the levels of malonaldehyde and 4-hydroxyalkenals in rat brain homogenates. Pomegranate extract exhibited scavenging activity against.OH and O(2)(.-). Anthocyanidins inhibited a Fenton reagent.OH generating system possibly by chelating with ferrous ion. Anthocyanidins scavenged O(2)(.)- in a dose-dependent manner. The ID(50) values of delphinidin, cyanidin, and pelargonidin were 2.4, 22, and 456 microM, respectively. In contrast, anthocyanidins did not effectively scavenge NO. Anthocyanidins inhibited H(2)O(2)-induced lipid peroxidation in the rat brain homogenates. The ID(50) values of delphinidin, cyanidin, and pelargonidin for them were 0.7, 3.5, and 85 microM, respectively. These findings suggest that the above anthocyanidins contribute to the antioxidant activity of pomegranate fruits.


  Cosmeceuticals containing herbs: fact, fiction, and future.:

 Dermatol Surg. 2005; 31(7 Pt 2):873-80; discussion 880 (ISSN: 1076-0512).Thornfeldt C.Oregon Health Sciences University, Portland, Oregon, USA. drcarl@epionce.com
 BACKGROUND: Modern medicine is rooted in ethnobotanical traditions using indigenous flora to treat symptoms of human diseases or to improve specific aspects of the body condition. Herbal medicine is now used by over half of the American population. Yet the American medical community generally lacks knowledge of the function, metabolism, interaction, adverse reactions, and preparation of herbal products. OBJECTIVE: Because over 60 botanicals are marketed in cosmeceutical formulations, dermatologists need to obtain working knowledge of the major botanicals. The preparation, traditional uses, mechanisms of action, human clinical data, adverse reactions, and interactions all impact herbal efficacy and are discussed below. METHOD: English-language medical journal and symposium searches. RESULTS: The most important botanicals pertaining to dermatologic uses, such as cosmeceuticals, include teas, soy, pomegranate, date, grape seed, Pycnogenol, horse chestnut, German chamomile, curcumin, comfrey, allantoin, and aloe. All are documented to treat dermatologic conditions. Only green and black tea, soy, pomegranate, and date have published clinical trials for the treatment of parameters of extrinsic aging. CONCLUSIONS: Preparation of botanical-based cosmeceuticals is complex. Very few of these products are supported by evidence-based science.

  Antioxidant activity of selected foodstuffs.:

 Int J Food Sci Nutr. 2004; 55(6):511-6 (ISSN: 0963-7486).Kelawala NS; Ananthanarayan L.Food and Fermentation Technology Department, Institute of Chemical Technology, University of Mumbai, Mumbai 400019, India.
 The growing interest in the substitution of synthetic food antioxidants by natural antioxidants and in the health implications of antioxidants as nutraceuticals has fostered research on vegetable sources and the screening of raw materials for identifying antioxidants. Plant and plant products have been used as a source of medicine for a long time. Among the more important constituents of edible plant products, low molecular weight antioxidants are the most important species. It is known that consumption of fruits and vegetables is essential for normal health of human beings. The aim of the present work was to evaluate the total antioxidant activity of selected natural food materials by an in vitro method involving the measurement of oxidation of linoleic acid by fluorimetry. Among the food materials chosen for the present study, pomegranate peel gave the maximum antioxidant activity due to the presence of its high polyphenolic content. At a concentration of 60 ppm, pomegranate peel powder reduced lipid peroxidation by 65% in an in vitro assay.

  The Herbal Alternatives for Menopause (HALT) Study: background and study design.:

 Maturitas. 2005; 52(2):134-46 (ISSN: 0378-5122).Newton KM; Reed SD; Grothaus L; Ehrlich K; Guiltinan J; Ludman E; Lacroix AZ.Center for Health Studies, Group Health Cooperative, Seattle, WA 98101, USA. newton.k@ghc.org
 We designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160 mg daily; (2) multibotanical (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625 mg +/- 2.5 mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women's Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry.

  Investigation of a betainic alkaloid from Punica granatum.:

 Nat Prod Res. 2005; 19(5):541-6 (ISSN: 1478-6419).Schmidt A; Mordhorst T; Nieger M.Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany. schmidt@ioc.tu-clausthal.de
 Spectroscopic investigations reveal that a hydroquinone pyridinium alkaloid isolated from the leaves of pomegranates Punica granatum L. (X-ray) exists as a mixture of a conjugated and a cross-conjugated heterocyclic mesomeric betaine in aqueous and DMSO-d6 solution. Twofold deprotonation yields an anionic tripole.

  The history and evolution of pessaries for pelvic organ prolapse.:

 Int Urogynecol J Pelvic Floor Dysfunct. 2006; 17(2):170-5 (ISSN: 0937-3462).Shah SM; Sultan AH; Thakar R.Department of Obstetrics and Gynaecology, Mayday University Hospital, 530 London Road, CR7 7YE, Croydon, U K.
 The use of pessaries for the treatment of genital prolapse dates back prior to the days of Hippocrates and their use has been documented in early Egyptian papyruses. Throughout the centuries remedies such as honey, hot oil, wine and fumes have been used as treatment. Mechanical methods included succussion and leg binding. Pomegranates were also common remedies. In the middle ages, linen and cotton wool soaked in many different potions were used. As new materials were discovered, pessaries evolved and began to resemble those used today. Cork and brass were soon replaced with rubber. Modern day pessaries are made of non-reactive silicone and come in various designs and sizes to suit each individual. Pessaries can be used as an interim measure for women who wish to complete childbearing or women awaiting surgery. It can also be used as a permanent measure for women who are unsuitable for surgery. It remains to be established whether the use of modern pessaries over prolonged periods of time can prevent progression of or even cure, prolapse.


  Quantitative analysis of flavan-3-ols in Spanish foodstuffs and beverages.:

 J Agric Food Chem. 2000; 48(11):5331-7 (ISSN: 0021-8561).de Pascual-Teresa S; Santos-Buelga C; Rivas-Gonzalo JC.Laboratorio de Nutrici??n y Bromatolog??a, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca 37007, Spain.
 An HPLC method, using detection after postcolumn derivatization with p-dimethylaminocynnamaldehyde (DMACA), was developed for the quantitative analysis of individual flavanols in food. This method was applied to flavanol determination in 56 different kinds of Spanish food products, including fruit, vegetables, legumes, beverages (cider, coffee, beer, tea, and wine), and chocolate. The determined compounds corresponded to the catechins and proanthocyanidin dimers and trimers usually present in food and, therefore, they were representative of the flavanols of low degree of polymerization consumed with the diet. The data generated could be used for calculation of the dietary intake of either individual or total flavanols, which would allow the further establishment of epidemiological correlations with the incidence of chronic diseases. Similar flavanol profiles were found in the different samples of a similar type of product, even though important variations could exist in the concentrations of total and individual flavanols among them. This was attributed to factors such as sample origin, stage of ripeness, post-harvesting conservation, and processing. Total flavanol contents varied from nondetectable in most of the vegetables to 184 mg/100 g found in a sample of broad bean. Substantial amounts were also found in some fruits, such as plum and apple, as well as in tea and red wine. Epicatechin was the most abundant flavanol, followed by catechin and procyanidin B2. In general, catechins were found in all the flavanol-containing products, but the presence of gallocatechins was only relevant in pomegranate, broad bean, lentil, grape, wine, beer, and tea, and most of the berries. Galloyled flavanols were only detected in strawberry, medlar, grape, and tea.

  Quantitative determination of the polyphenolic content of pomegranate peel.:

 Z Lebensm Unters Forsch. 1996; 203(4):374-8 (ISSN: 0044-3026).Ben Nasr C; Ayed N; Metche M.Facult?? des sciences de Bizerte, D??partement de chimie, Zarzouna, Tunisia.
 The quantitative determination of total phenols, ellagic tannins and gallic and ellagic acids in the peel of the Tunisian pomegranate variety Chelfi, has been carried out. The ellagic tannin content is prominently less than the amount of total phenols, which led us to look for the presence of the condensed tannins. The determination of the content of catechic tannins in eight Tunisian varieties of the pomegranate was carried out using weekly samples over a period of 2 months.


  Scientific References:

  1.Pomegranate:Ancient Fruit of Life Yields Modern Promise...
  2.Pomegranate and Its Modern Research Update: