Pomegranate

 

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Clinical Studies


Pomegranate extract is used to prevent cancer and as an antiviral and antibacterial. Pomegranate extract has lipophilic antioxidant activity and free radical scavenging capability. Pomegranate extract inhibits lipid peroxidation at lower concentrations than vitamin E. Pomegranate also seems to have antibacterial, anti-inflammatory and antimutagenic activity. It has been proven to cause apoptosis (natural cell death) in cancer cells without harming healthy cells as chemotherapy does. Pomegranate extract has no side effects and no known drug interactions, and may be the most potent way to prevent cancer, strengthen the immune system, prevent heart disease, liver fibrosis, promote wound healing and strengthen connective tissue (which may keep cancer cells from spreading).

 


 

Published Clinical Studiescl top

Antibacterial action of several tannins against Staphylococcus aureus.1

Akiyama H, Fujii K, Yamasaki O, Oono T, Iwatsuki K.

 

Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho 2-5-1, Okayama 700-8558, Japan. akiyamah@cc.okayama-u.ac.jp

We examined the antibacterial action of several tannins on plasma coagulation by Staphylococcus aureus and the effect of conventional chemotherapy combined with tannic acid below the MIC. Coagulation was inhibited in plasma containing tannic acid (100 mg/L), gallic acid (5000 mg/L), ellagic acid (5000 mg/L), (-)-epicatechin (1500 mg/L), (-)-epicatechin gallate (500 mg/L) or (-)-epigallocatechin gallate (200 mg/L) after incubation for 24 h. All tannins inhibited coagulation at a concentration below the MIC. The MICs of oxacillin and cefdinir for S. aureus were reduced to < or = 0.06 mg/L in Mueller-Hinton agar plates with tannic acid (100 mg/L) at a concentration below the MIC. The antistaphylococcal activity of tannic acid was reduced in plates with 10% rabbit blood, but not in those with 10% rabbit plasma. Membranous structures formed in a culture medium containing equal proportions of plasma and tryptic soy broth after incubation for 24 h. The colony counts of S. aureus in membranous structures in the medium containing oxacillin (40 mg/L) and tannic acid (100 mg/L) were c. 10-fold lower than those in medium containing oxacillin (40 mg/L) alone (P < 0.01). Tannic acid merits further investigation as a possible adjuvant agent against S. aureus skin infections treated with beta-lactam antibiotics.

PMID: 11581226 [PubMed - indexed for MEDLINE]

 

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 2
Effects of ellagic acid by oral administration on N-acetylation and metabolism of 2-aminofluorene in rat brain tissues.

Lin SS, Hung CF, Ho CC, Liu YH, Ho HC, Chung JG.

 

Department of Radiological Technology, Chungtai Institute of Health Sciences and Technology, Taichung, Taiwan, Republic of China.

Numerous studies have demonstrated that the Acetyl Coenzyme A-dependent arylamine NAT enzyme exist in many tissues of experimental animals including humans, and that NAT has been shown to be exist in mouse brain tissue. Increased NAT activity levels are associated with increased sensitivity to the mutagenic effects of arylamine carcinogens. Attenuation of liver NAT activity is related to breast and bladder cancer processes. Therefore, the effects of ellagic acid (EA) on the in vitro and in vivo N-acetylation of 2-aminofluorene (AF) were investigated in cerebrum, cerebellum and pineal gland tissues from male Sprague-Dawley rats. For in vitro examination, cytosols with or without EA (0.5-500 microM) co-treatment decreased 7-72%, 15-63% and 10-78% of AF acetylation for cerebrum, cerebellum and pineal gland tissues, respectively. For in vivo examination, EA and AF at the same time treated groups with all 3 examined tissues did show significant differences (the changes of total amounts of AF and AF metabolites based on the Anova analysis) when compared to the ones without EA cotreatment rats. The pretreatment of male rats with EA (10 mg/kg) 24 hr prior to the administration of AF (50 mg/kg) (one day of EA administration suffice to induce large changes in phase II enzyme activity) resulted in a 76% decrease in total AF and metabolites in pineal gland but did not show significant differences in cerebrum and cerebellum tissues. This is the first demonstration to show that EA decreases the N-acetylation of carcinogens in rat brain tissues.

PMID: 11071370 [PubMed - indexed for MEDLINE]

 

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 3
Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid--extensive binding to protein and DNA.

Whitley AC, Stoner GD, Darby MV, Walle T.

 

Department of Cellular and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, PO Box 250505, Charleston, SC 29425, USA.

Ellagic acid (EA), a polyphenol present in many berries, has been demonstrated to be preventive of esophageal cancer in animals both at the initiation and promotion stages. To be able to extrapolate these findings to humans we have studied the transcellular absorption and epithelial cell accumulation of [14C]EA in the human intestinal Caco-2 cells. The apical (mucosal) to basolateral (serosal) transcellular transport of 10 microM [14C]EA was minimal with a P(app) of only 0.13 x 10(-6)cm/s, which is less than for the paracellular transport marker mannitol. In spite of observations of basolateral to apical efflux, Caco-2 cell uptake studies showed high accumulation of EA in the cells (1054+/-136 pmol/mg protein), indicating facile absorptive transport across the apical membrane. Surprisingly, as much as 93% of the cellular EA was irreversibly bound to macromolecules (982+/-151 pmol/mg protein). To confirm the irreversible nature of the binding to protein, Caco-2 cells treated with 10 microM [14C]EA were subjected to SDS-PAGE analysis. This resulted in radiolabeled protein bands trapped in the stacking gel, consistent with [14C]EA-crosslinked proteins. Treatment of Caco-2 cells with 10 microM [14C]EA also revealed irreversible binding of EA to cellular DNA as much as five times higher than for protein (5020+/-773 pmol/mg DNA). Whereas the irreversible binding to protein required oxidation of EA by reactive oxygen species, this did not seem to be the case with the DNA binding. The avid irreversible binding to cellular DNA and protein may be the reason for its highly limited transcellular absorption. Thus, EA appears to accumulate selectively in the epithelial cells of the aerodigestive tract, where its cancer preventive actions may be displayed.

PMID: 12963477 [PubMed - indexed for MEDLINE]

 

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 4
Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay.

Festa F, Aglitti T, Duranti G, Ricordy R, Perticone P, Cozzi R.

 

Dipartimento di Biologia, Universita degli Studi Roma TRE, Italy.

Oxidative stress due to oxygen and various radical species is associated with the induction of DNA single- and double-strand breaks and is considered to be a first step in several human degenerative diseases, cancer and ageing. Naturally occurring antioxidants are being extensively analysed for their ability to protect DNA against such injury. We studied three naturally occuring compounds, Ascorbic Acid, Melatonin and Ellagic acid, for their ability to modulate DNA damage produced by two strong radical oxygen inducers (H2O2 and Bleomycin) in cultured CHO cells. The alkaline Comet assay was used to measure DNA damage and a cytofluorimetric analysis was performed to reveal the intracellular oxidative species. The data showed a marked reduction of H2O2- and Bleomycin-induced DNA damage exerted by Ellagic Acid. On the contrary Ascorbic acid and Melatonin appeared to induce a slight increase in DNA damage per se. In combined treatments, they caused a slight reduction of H2O2-induced damage, but they did not efficiently modulate the Bleomycin-induced one. The Dichlorofluorescein diacetate (DCFH-DA) cytofluorimetric test confirmed the strong scavenging action exerted by Ellagic Acid.

PMID: 11911267 [PubMed - indexed for MEDLINE]

 

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 5
Ellagic [correction of ellagica] acid inhibits arylamine N-acetyltransferase activity and DNA adduct formation in human bladder tumor cell lines (T24 and TSGH 8301).

Lin SS, Hung CF, Tyan YS, Yang CC, Hsia TC, Yang MD, Chung JG.

 

Department of Radiological Technology, Chungtai Institute of Health Sciences and Technology, Taichung, Taiwan, Republic of China.

The fact that vitamin C (ascorbic acid) exhibits a protective effect in certain types of cancer is well documented. Our previous studies demonstrated that human bladder tumor cell line (T24) has N-acetyltransferase (NAT) activity in cytosols and intact cells. The present studies examined the inhibition of arylamine NAT activity and carcinogen (2-aminofluorene)-DNA adduct formation by ellagic acid (EA) in human bladder tumor cell lines (T24 and TSGH 8301). Two assay systems were performed, one with cellular cytosols (9,000 g supernatant), the other with intact bladder tumor cell suspensions. NAT activity and 2-aminofluorene-DNA adduct formation in T24 and TSGH 8301 cells was inhibited by EA in a dose-dependent manner in both systems, i.e.. the greater the concentration of EA in the reaction the greater the inhibition of NAT activity (dose- and time-course dependent effects). The data also indicated that EA decreased the apparent Km and Vmax of NAT enzymes from T24 and TSGH 8301 cells in cytosols. NAT activity and 2-aminofluorene-DNA adducts in T24 is higher than in TSGH 8301. This report is the first to demonstrate that EA affects human bladder tumor cell NAT activity.

PMID: 11828989 [PubMed - indexed for MEDLINE]

 

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 6
Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing.

Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA.

 

Department of Pomology, University of California, Davis, California 95616, USA.

The antioxidant activity of pomegranate juices was evaluated by four different methods (ABTS, DPPH, DMPD, and FRAP) and compared to those of red wine and a green tea infusion. Commercial pomegranate juices showed an antioxidant activity (18-20 TEAC) three times higher than those of red wine and green tea (6-8 TEAC). The activity was higher in commercial juices extracted from whole pomegranates than in experimental juices obtained from the arils only (12-14 TEAC). HPLC-DAD and HPLC-MS analyses of the juices revealed that commercial juices contained the pomegranate tannin punicalagin (1500-1900 mg/L) while only traces of this compound were detected in the experimental juice obtained from arils in the laboratory. This shows that pomegranate industrial processing extracts some of the hydrolyzable tannins present in the fruit rind. This could account for the higher antioxidant activity of commercial juices compared to the experimental ones. In addition, anthocyanins, ellagic acid derivatives, and hydrolyzable tannins were detected and quantified in the pomegranate juices.

PMID: 11052704 [PubMed - indexed for MEDLINE]

 

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Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxicity.7

Thresiamma KC, George J, Kuttan R.

 

Amala Cancer Research Centre, Amala Nagar, Trichur, Kerala State, India.

Induction of micronuclei and chromosomal aberrations produced by whole body exposure of r-radiation (1.5-3.0 Gy) in mice was found to be significantly inhibited by oral administration of natural antioxidants, curcumin (400 micro moles), ellagic acid (200 micro moles) and bixin (200 micro moles) per kilogram body weight. These antioxidants induced inhibition of micronucleated polychromatic and normochromatic erythrocytes, was comparable with alpha-tocopherol (200 micro moles) administration. Curcumin and ellagic acid were also found to significantly reduce the number of bone marrow cells with chromosomal aberrations and chromosomal fragments as effectively as alpha-tocopherol. Moreover, administration of antioxidants inhibited the DNA strand breaks produced in rat lymphocytes upon radiation as seen from the DNA unwinding studies. These results indicated that antioxidant curcumin, ellagic acid and bixin provide protection against chromosome damage produced by radiation.

PMID: 10089063 [PubMed - indexed for MEDLINE]

 

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[The protective action of ellagic acid in experimental myocarditis]8

Iakovleva LV, Ivakhnenko AK, Buniatian ND.

 

Central Research Laboratory, Ukranian Pharmaceutical Academy, Kharkov, Ukraine.

The article presents the material on the study of the cardioprotective effect of ellagic acid on a model of neoepinephrine myocarditis in rats. In doses of 0.5-1 mg/kg ellagic acid causes a marked antioxidant effect. Restores the disturbed myocardial functions. The reference-agent vitamin E (50 mg/kg) yields to ellagic acid as a cardioprotector. The effect of 0.5 mg/kg of ellagic acid was more stable than that of a 1 mg/kg dose. The cardioprotective activity of the drugs under study was determined according to the POL parameters in a myocardial homogenate and blood serum and according to the EEG parameters and the degree of cardiomyocyte cytolysis.

PMID: 9690073 [PubMed - indexed for MEDLINE]

 

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Inhibition of liver fibrosis by ellagic acid.9

Thresiamma KC, Kuttan R.

 

Amala Cancer Research Centre, Amala Nagar, Trichur, Kerala.

Chronic administration of carbon tetrachloride in liquid paraffin (1.7) ip; 0.15 ml, (20 doses) has been found to produce severe hepatotoxicity, as seen from the elevated levels of serum and liver glutamate-pyruvate transaminase, alkaline phosphatase and lipid peroxides. The chronic administration of carbon tetrachloride was also found to produce liver fibrosis as seen from pathological analysis as well as elevated liver-hydroxy proline. Oral administration of ellagic acid was found to significantly reduce the elevated levels of enzymes, lipid peroxide and liver hydroxy proline in these animals and rectified liver pathology. These results indicate that ellagic acid administration orally can circumvent the carbon tetrachloride toxicity and subsequent fibrosis.

PMID: 9055108 [PubMed - indexed for MEDLINE]