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Antioxidant Activity of Ellagic Acid

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

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.

Antioxidant properties of novel preparations-bioflavonoid derivatives and tannins.

[Article in Russian] Iakovleva LV, Gerasimova OA, Karbusheva IV, Ivakhnenko AK, Buniatian ND, Sakharova TS.
Central Research Laboratory, Ukrainian Pharmaceutical Academy, ul. Pushkinskaya 53, Kharkov, 310002 Ukraine.

New medicinal plant preparations of polyphenol nature, representing the derivatives of bioflavonoids (piflamin) and ellagotannins (altan and ellagic acid) were experimentally studied. The drugs exhibited antioxidant properties, which were manifested by inhibition of a pathological lipid peroxidation, restoration of the functional activity of the antioxidant system components, and stabilization of the hepatocyte membranes.

Antioxid Redox Signal 2001 Dec;3(6):995-1008

Chemical studies of proanthocyanidins and hydrolyzable tannins.
Bors W, Foo LY, Hertkorn N, Michel C, Stettmaier K.

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.

Chemical studies of proanthocyanidins and hydrolyzable tannins.
Bors W, Foo LY, Hertkorn N, Michel C, Stettmaier K.
Institut fur Strahlenbiologie, GSF Forschungszentrum fur Umwelt und Gesundheit, Neuherberg, Germany. [email protected]

We investigated a number of natural polyphenols representing flavan-3-ols, gallotannins, and ellagitannins with regard to their antioxidant potential. For this purpose we used pulse radiolysis to determine scavenging rate constants with hydroxyl radicals and decay rates of the respective aroxyl radicals and EPR spectroscopy to identify the radicals after in situ oxidation. Using NMR spectroscopy, we could confirm phenolic coupling reactions of epigallocatechin gallate and pentagalloyl glucose after radical-induced oxidation.

Agric Food Chem. 2002 Aug 28;50(18):5191-6.

Ellagitannins, flavonoids, and other phenolics in red raspberries and their contribution to antioxidant capacity and vasorelaxation properties.

Mullen W, McGinn J, Lean ME, MacLean MR, Gardner P, Duthie GG, Yokota T, Crozier A.
Plant Products and Human Nutrition Group, Graham Kerr Building, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, United Kingdom.

Analysis of extracts of Glen Ample raspberries (Rubus idaeus L.) by gradient, reverse phase HPLC with diode array and tandem mass spectrometry identified eleven anthocyanins, including cyanidin-3-sophoroside, cyanidin-3-(2(G)-glucosylrutinoside), cyanidin-3-glucoside, cyanidin-3-rutinoside, pelargonidin-3-sophoroside, pelargonidin-3-(2(G)-glucosylrutinoside), and pelargonidin-3-glucoside. Significant quantities of an ellagitannin, sanguiin H-6, with an M(r) of 1870 were detected along with lower levels of a second ellagitannin, lambertianin C, which has an M(r) of 2804. Other phenolic compounds that were detected included trace levels of ellagic acid and its sugar conjugates along with one kaempferol- and four quercetin-based flavonol conjugates. Fractionation by preparative HPLC revealed that sanguiin H-6 was a major contributor to the antioxidant capacity of raspberries together with vitamin C and the anthocyanins. Vasodilation activity was restricted to fractions containing lambertianin C and sanguiin H-6.


G1 arrest refers to a stsage of mitosis or cell division and replication. Apoptosis refers to programmed tumor cell death.

1: Cancer Lett 1999 Mar 1;136(2):215-21, p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW.
Cancer Prevention Program, Hollings Cancer Center, Medical University of South Carolina, Charleston 29425, USA. [email protected]

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.


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