Ellagic Acid, Technical information and research

Ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin. MESH TERMS: Animal Anticarcinogenic Agents/*Therapeutic Use Chemoprevention Diethylnitrosamine/*Antagonists and Inhib Ellagic Acid/*Therapeutic Use Glutathione/Metabolism Lipid Peroxidation/Drug Effects Lung Neoplasms/*Prevention and Control Male Mice Microsomes/Drug Effects/Metabolism Oxidation-Reduction Quercetin/*Therapeutic Use LANGUAGE: ENG PUBLICATION TYPE: JOURNAL ARTICLE TITLE ABBREVIATION: Food Chem Toxicol YEAR: 1999 AUTHOR: Khanduja KL, Gandhi RK, Pathania V, Syal N TITLE: Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. SOURCE: Food Chem Toxicol; 37(4):313-8 1999 UI: 99345316 ABSTRACT: The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin. MESH TERMS: Animal Anticarcinogenic Agents/*Therapeutic Use Chemoprevention Diethylnitrosamine/*Antagonists and Inhib Ellagic Acid/*Therapeutic Use Glutathione/Metabolism Lipid Peroxidation/Drug Effects Lung Neoplasms/*Prevention and Control Male Mice Microsomes/Drug Effects/Metabolism Oxidation-Reduction Quercetin/*Therapeutic Use LANGUAGE: ENG PUBLICATION TYPE: JOURNAL ARTICLE TITLE ABBREVIATION: Food Chem Toxicol YEAR: 1999 AUTHOR: Khanduja KL, Gandhi RK, Pathania V, Syal N TITLE: Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. SOURCE: Food Chem Toxicol; 37(4):313-8 1999 UI: 99345316 ABSTRACT: The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin. MESH TERMS: Animal Anticarcinogenic Agents/*Therapeutic Use Chemoprevention Diethylnitrosamine/*Antagonists and Inhib Ellagic Acid/*Therapeutic Use Glutathione/Metabolism Lipid Peroxidation/Drug Effects Lung Neoplasms/*Prevention and Control Male Mice Microsomes/Drug Effects/Metabolism Oxidation-Reduction Quercetin/*Therapeutic Use LANGUAGE: ENG PUBLICATION TYPE: JOURNAL ARTICLE TITLE ABBREVIATION: Food Chem Toxicol YEAR: 1999 AUTHOR: Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW TITLE: p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. SOURCE: Cancer Lett; 136(2):215-21 1999 UI: 99281882 ABSTRACT: Ellagic acid is a phenolic compound present in fruits and nuts including raspberries, strawberries and walnuts. It is known to inhibit certain carcinogen-induced cancers and may have other chemopreventive properties. The effects of ellagic acid on cell cycle events and apoptosis were studied in cervical carcinoma (CaSki) cells. We found that ellagic acid at a concentration of 10(-5) M induced G arrest within 48 h, inhibited overall cell growth and induced apoptosis in CaSki cells after 72 h of treatment. Activation of the cdk inhibitory protein p21 by ellagic acid suggests a role for ellagic acid in cell cycle regulation of cancer cells. MESH TERMS: Apoptosis* Blotting, Western Cell Division/Drug Effects Cyclins/*Biosynthesis Dose-Response Relationship, Drug DNA/Biosynthesis DNA Fragmentation Ellagic Acid/*Pharmacology Enzyme Inhibitors/*Metabolism Flow Cytometry G1 Phase/*Drug Effects Human Neoplasms/*Metabolism Protein p53/*Biosynthesis Time Factors Tumor Cells, Cultured LANGUAGE: ENG PUBLICATION TYPE: JOURNAL ARTICLE TITLE ABBREVIATION: Cancer Lett YEAR: 1999 TITLE: [The protective action of ellagic acid in experimental myocarditis] AUTHOR: Iakovleva LV, Ivakhnenko AK, Buniatian ND SOURCE: Eksp Klin Farmakol; 61(3):32-4 1998 UI: 98354527 ABSTRACT: 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. LANGUAGE: RUS PUBLICATION TYPE: JOURNAL ARTICLE TITLE ABBREVIATION: Eksp Klin Farmakol YEAR: 1998 ADDRESS: Central Research Laboratory, Ukranian Pharmaceutical Academy, Kharkov, Ukraine. AUTHOR: Chen Z, Gundimeda U, Gopalakrishna R TITLE: Ellagic acid induces oxidative inactivation of protein kinase C by modifying both catalytic and regulatory domains (Meeting abstract). SOURCE: Proc Annu Meet Am Assoc Cancer Res; 38:A1395 1997 UI: 98638395 ABSTRACT: Ellagic acid is a polyphenol found in fruits and vegetables, and has been shown to have cancer chemopreventive activity. The mechanism of its antitumor promoting activity is not known. Since protein kinase C (PKC) serves as a receptor for tumor promoters as well as can be oxidatively modified by phenolic compounds, we have determined whether ellagic acid can directly regulate this enzyme. When PKC was preincubated with ellagic acid and then assayed with a low (5 uM) or high (100 uM) concentration of ATP, the enzyme was inhibited with an IC50 of 1 and 4 uM, respectively. Detailed studies revealed that this was due to an irreversible inactivation of the enzyme caused by a redox modification. Ellagic acid-iron complex can inactivate PKC without the need for other metals. Both catalytic and regulatory domains of PKC were modified by ellagic as determined by the loss of kinase activity and phorbol ester binding. But the catalytic domain was 3-fold more sensitive. The thiol agents and vitamin C inhibited this inactivation. In JB6 cells, ellagic acid at low (less than 1 to 5 uM) concentrations induced a modification of PKC which was reversed by an endogenous reduction mechanism, while at higher (5 to 25 uM) concentrations, it induced an irreversible inactivation. Taken together these results suggest that the antitumor promoting action of ellagic acid may be mediated in part by inducing a redox modification of PKC. LANGUAGE: ENG PUBLICATION TYPE: MEETING ABSTRACTS TITLE ABBREVIATION: Proc Annu Meet Am Assoc Cancer Res YEAR: 1997 Ellagic Acid is a phenolic compound that has become a known as a potent anti-carcinogenic/anti-mutagenic compound. It also has anti-bacterial and anti-viral properties. Ellagic acid itself is not thought to be naturally present in plants. Instead, polymers of gallic acid and hexahydroxydipenoyl (HHDP) are linked to glucose centers to form the class of compounds known as ellagitannins. When two gallic acid groups become linked side-by-side within a tannin molecule and HHDP group is formed.

Ellagic acid is the result when the HHDP group is cleaved from the tannin molecule and spontaneously rearranges. It is the ellagitannins that are present in red raspberries. Some articles in which ellagitannins are quantified refer to ellagic acid because quantitation of ellagitannins is done by breaking them down into ellagic acid subunits and quantifying the subunits.

The Meeker red raspberry is the best source of ellagic acid followed by Chilliwack and Willamette. The Meeker variety is specific to the Pacific Northwest---grown primarily for commercial use in Washington State. The Chilliwack and Willamette varieties contain lesser variations of ellagic acid. Both of these varieties are grown in the Pacific Northwest and may be found in lesser volumes outside the United States

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