Scientific Researches On:
Ellagic Acid (Raspberry/Pomegranate
Extract)
USA National Center for Biotechnology Information
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1:
Nutr Cancer. 2008 Mar-Apr;60(2):227-34.
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Dietary berries and ellagic acid diminish
estrogen-mediated mammary tumorigenesis in ACI rats.
Aiyer HS,
Srinivasan C,
Gupta RC.
Brown Cancer Center, University of Louisville,
Louisville, Kentucky 40202, USA.
Estrogen acts as a complete mammary carcinogen in ACI
rats. Prevention studies in this model allowed us to
identify agents that are effective against
estrogen-induced mammary carcinogenesis. In this study,
we investigated efficacy of dietary berries and ellagic
acid to reduce estrogen-mediated mammary tumorigenesis.
Female ACI rats (8-9 wk) were fed either AIN-93M diet (n
= 25) or diet supplemented with either powdered
blueberry (n = 19) and black raspberry (n = 19) at 2.5%
wt/wt each or ellagic acid (n = 22) at 400 ppm. Animals
received implants of 17beta-estradiol 2 wk later, were
palpated periodically for mammary tumors, and were
euthanized after 24 wk. No differences were found in
tumor incidence at 24 wk; however, tumor volume and
multiplicity were reduced significantly after
intervention. Compared with the control group (average
tumor volume = 685 +/- 240 mm3 and tumor multiplicity =
8.0 +/- 1.3), ellagic acid reduced the tumor volume by
75% (P < 0.005) and tumor multiplicity by 44% (P <
0.05). Black raspberry followed closely, with tumor
volume diminished by > 69% (P < 0.005) and tumor
multiplicity by 37% (P = 0.07). Blueberry showed a
reduction (40%) only in tumor volume. This is the first
report showing the significant efficacy of both ellagic
acid and berries in the prevention of solely
estrogen-induced mammary tumors.
Publication Types:
PMID: 18444155 [PubMed - in process]
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Chemoprevention by white currant is mediated by the
reduction of nuclear beta-catenin and NF-kappaB levels
in Min mice adenomas.
Rajakangas J,
Misikangas M,
Päivärinta E,
Mutanen M.
Dept. of Applied Chemistry and Microbiology (Nutrition),
University of Helsinki, P.O. Box 66, 00014 Helsinki,
Finland. johanna.rajakangas@helsinki.fi
BACKGROUND: Berries are a good natural source of
phenolic compounds and many berries or their compounds
have been shown to be chemopreventive. White currant is
an interesting berry, as it contains low levels of
dominant berry phenolics such as ellagic acid,
anthocyanins and other flavonoids. AIMS OF THE STUDY: To
study if white currant is chemopreventive in an
experimental model for intestinal tumorigenesis and
further study the effects on beta-catenin and NF-kappaB
signaling pathways. METHODS: Multiple intestinal
neoplasia (Min) mice were fed an AIN-93G based control
diet or a diet containing 10% freeze dried white currant
(Ribes x pallidum) for 10 weeks. Cell signaling
parameters were analysed from intestinal adenomas and
surrounding mucosa by Western blotting and
immunohistochemistry. RESULTS: The white currant diet
reduced the number of adenomas from 81 (min-max 47-114)
to 51 (36-84) in the total small intestine of Min mice
(P<0.02). Most of the adenomas develop in the distal
part of the small intestine, and in this area white
currant reduced the number from 49 to 29.5 (P<0.01) and
also the size of the adenomas from 0.88 mm to 0.70 mm
(P<0.02). In the colon white currant increased the
number of adenomas (0.3+/-0.6 vs. 0.8+/-0.6, mean +/-
SD, P<0.05), but did not affect the size. White currant
reduced nuclear beta-catenin and NF-kappaB protein
levels in the adenomas (P<0.05 and P<0.02,
respectively). They were correlated with the size of
adenomas (P<0.01). CONCLUSIONS: This study shows that
white currant is effective in preventing cancer
initiation and progression in the Min mouse. Whether the
positive effects are due to its special phenolic
composition needs to be studied in more detail.
Publication Types:
PMID: 18389329 [PubMed - in process]
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Ellagic acid, pomegranate and prostate cancer -- a
mini review.
Bell C,
Hawthorne S.
School of Pharmacy, Medical Biology Centre, Queens
University of Belfast, 97 Lisburn Road, Belfast, BT9
7BL, UK.
There is currently a shifting focus towards finding
natural compounds that may prevent or treat cancer, due
to the problems that exist with current chemotherapeutic
regimens. The fruit of the Punica granatum (pomegranate)
contains hundreds of phytochemicals and pomegranate
extracts have recently been shown to exhibit antioxidant
properties, thought to be due to the action of ellagic
acid, the main polyphenol in pomegranate. In this mini
review the effects of pomegranate extracts and ellagic
acid on the proliferation of prostate cancer cells and
their future potential are discussed.
Publication Types:
PMID: 18237460 [PubMed - indexed for MEDLINE]
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Isolation and identification of strawberry phenolics
with antioxidant and human cancer cell antiproliferative
properties.
Zhang Y,
Seeram NP,
Lee R,
Feng L,
Heber D.
Center for Human Nutrition, David Geffen School of
Medicine, University of California, Los Angeles,
California 90095, USA.
Studies suggest that consumption of berry fruits,
including strawberries ( Fragaria x ananassa Duch.), may
have beneficial effects against oxidative stress
mediated diseases such as cancer. Berries contain
multiple phenolic compounds, which are thought to
contribute to their biological properties. Comprehensive
profiling of phenolics from strawberries was previously
reported using high-performance liquid chromatography
with mass spectrometry (HPLC-MS) detection. The current
study reports the isolation and structural
characterization of 10 phenolic compounds from
strawberry extracts using a combination of Amberlite
XAD16-resin and C18 columns, HPLC-UV, and nuclear
magnetic resonance (NMR) spectroscopy methods. The
phenolics were cyanidin-3-glucoside ( 1), pelargonidin
(2), pelargonidin-3-glucoside (3),
pelargonidin-3-rutinoside (4), kaempferol (5), quercetin
(6), kaempferol-3-(6'-coumaroyl)glucoside) (7),
3,4,5-trihydroxyphenyl-acrylic acid (8), glucose ester
of ( E)- p-coumaric acid (9), and ellagic acid .
Strawberry crude extracts and purified compounds 1- 10
were evaluated for antioxidant and human cancer cell
antiproliferative activities by the Trolox equivalent
antioxidant capacity (TEAC) and luminescent ATP cell
viability assays, respectively. Among the pure
compounds, the anthocyanins 1 (7156 microM Trolox/mg), 2
(4922 microM Trolox/mg), and 4 (5514 microM Trolox/mg)
were the most potent antioxidants. Crude extracts (250
microg/mL) and pure compounds (100 microg/mL) inhibited
the growth of human oral (CAL-27, KB), colon (HT29,
HCT-116), and prostate (LNCaP, DU145) cancer cells with
different sensitivities observed between cell lines.
This study adds to the growing body of data supporting
the bioactivities of berry fruit phenolics and their
potential impact on human health.
PMID: 18211028 [PubMed - indexed for MEDLINE]
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Potential of radiosensitizing agents in cancer
chemo-radiotherapy.
Girdhani S,
Bhosle SM,
Thulsidas SA,
Kumar A,
Mishra KP.
Radiation Biology and Health Sciences Division Bhabha
Atomic Research Centre, Mumbai 400 085, India.
Potential of herbs and other plant-based formulations
have been increasingly recognized in prevention and
treatment of human diseases including cancer. There
exist enormous prospect for screening and evaluation of
herbal/plant products for developing effective
radiosensitization and radioprotection relevant to
nuclear research program. Investigations in our
laboratory have focused on the mechanism of activity of
variety of anticancer and antioxidant agents, namely,
Eugenol, (EU), Ellagic acid (EA), Triphala (TPL),
Tocopherol Succinate (TOS) and Arachidonic acid on
normal and cancer cells with view to design effective
protocols in practical radioprotection and cancer
radiotherapy. This paper is mainly focused on studies on
cytotoxic effects on cancer cell lines. Results have
shown that these agents produced radiosensitizing action
involving oxidative damage, membrane alteration and
damage to nucleic acid in various human cell lines.
Studies were performed employing fluorescence probes and
electron spin resonance methods and gel electrophoresis
protocols. It has been found that cytotoxic effect was
induced by initiating membrane oxidative damage and by
triggering intracellular generation of reactive oxygen
species (ROS) by gamma radiation in combination with
phytochemicals like TPL, EA and TOS in tumor cell line
Ehrlich Ascites (EAC), Human cervical (HeLa) and breast
(MCF-7) cells. Membrane damage and ROS generation was
measured by DPH and DCF-FDA fluorescent probes
respectively after exposure to low to moderate doses of
gamma radiation. This talk will present the cytotoxic
effects of phytochemicals in combination with ionizing
radiation. It is emphasized that modulation of membrane
peroxidative damage and intra cellular ROS may help
achieve efficient killing of cancer cells which may
provide a new approach to developing effective treatment
of cancer.
Publication Types:
PMID: 17998642 [PubMed - indexed for MEDLINE]
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Iberian pig as a model to clarify obscure points in
the bioavailability and metabolism of ellagitannins in
humans.
Espín JC,
González-Barrio R,
Cerdá B,
López-Bote C,
Rey AI,
Tomás-Barberán FA.
Research Group on Quality, Safety and Bioactivity of
Plant Foods, Department of Food Science and Technology,
CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo,
Murcia, Spain.
Ellagitannin-containing foods (strawberries, walnuts,
pomegranate, raspberries, oak-aged wine, etc.) have
attracted attention due to their cancer chemopreventive,
cardioprotective, and antioxidant effects. Ellagitannins
(ETs) are not absorbed as such but are metabolized by
the intestinal flora to yield urolithins
(hydroxydibenzopyran-6-one derivatives). In this study,
Iberian pig is used as a model to clarify human ET
metabolism. Pigs were fed either cereal fodder or
acorns, a rich source of ETs. Plasma, urine, bile, lumen
and intestinal tissues (jejunum and colon), feces,
liver, kidney, heart, brain, lung, muscle, and
subcutaneous fat tissue were analyzed. The results
demonstrate that acorn ETs release ellagic acid (EA) in
the jejunum, then the intestinal flora metabolizes EA
sequentially to yield tetrahydroxy- (urolithin D),
trihydroxy- (urolithin C), dihydroxy- (urolithin A), and
monohydroxy- (urolithin B) dibenzopyran-6-one
metabolites, which were absorbed preferentially when
their lipophilicity increased. Thirty-one ET-derived
metabolites were detected, including 25 urolithin and 6
EA derivatives. Twenty-six extensively conjugated
metabolites were detected in bile, glucuronides and
methyl glucuronides of EA and particularly urolithin A,
C, and D derivatives, confirming a very active
enterohepatic circulation. Urolithins A and B as well as
dimethyl-EA-glucuronide were detected in peripheral
plasma. The presence of EA metabolites in bile and in
urine and its absence in intestinal tissues suggested
its absorption in the stomach. Urolithin A was the only
metabolite detected in feces and together with its
glucuronide was the most abundant metabolite in urine.
No metabolites accumulated in any organ analyzed. The
whole metabolism of ETs is shown for the first time,
confirming previous studies in humans and explaining the
long persistency of urolithin metabolites in the body
mediated by an active enterohepatic circulation.
Publication Types:
PMID: 17990850 [PubMed - indexed for MEDLINE]
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Purinergic regulation of angiogenesis by human breast
carcinoma-secreted nucleoside diphosphate kinase.
Rumjahn SM,
Javed MA,
Wong N,
Law WE,
Buxton IL.
Department of Pharmacology MS318, University of Nevada
School of Medicine, 1664 N Virginia Street, Reno, NV
89557, USA.
MDA-MB-435S human breast cancer cells (435S) secrete
nucleoside diphosphate kinase (NDPK) that supports
metastases and is inhibited by epigallocatechin gallate
(EGCG) and ellagic acid (EA). We hypothesise that 435S
cell-secreted NDPK-B supports tumour formation by
modulating ATP levels locally to activate endothelial
cell (EC) P2Y receptor-mediated angiogenesis.
Epigallocatechin gallate (IC50=8-10 microM) and EA
(IC50=2-3 microM) suppressed 435S cell growth, but had
less effect on human CD31+ EC growth. Epigallocatechin
gallate (IC50=11 microM) and EA (IC50=1 microM) also
prevented CD31+ EC tubulogenesis on Matrigeltrade mark.
435S cell-conditioned media induced tubulogenesis in a
cell number, time, and nucleotide-dependent manner.
Ellagic acid (1 microM), but not equimolar EGCG, reduced
cell number-dependent angiogenesis. P2Y 1 receptor
activation by NDPK-generated nucleotide (100 microM ATP)
or by 10 microM 2-methyl-thio-ATP (2MS-ATP) promoted
tubulogenesis on collagen and was blocked by the P2Y 1
antagonist MRS2179 (10 microM). Physiological amounts of
purified as well as 435S cell-secreted NDPK also
promoted angiogenesis that was attenuated by NDPK
depletion or 10 microM MRS2179, indicating a P2Y 1
receptor-mediated pathway. These results support the
notion that secreted NDPK mediates angiogenesis via P2Y
receptor signalling and suggests that novel inhibitors
of NDPK may be useful as therapeutics.
Publication Types:
PMID: 17940513 [PubMed - indexed for MEDLINE]
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Anticancer and antioxidant tannins from Pimenta
dioica leaves.
Marzouk MS,
Moharram FA,
Mohamed MA,
Gamal-Eldeen AM,
Aboutabl EA.
Natural Products Group, Nobel Project Laboratory,
National Research Centre, El-Behoos St., Dokki, Cairo,
Egypt.
Two galloylglucosides, 6-hydroxy-eugenol
4-O-(6'-O-galloyl)-beta-D-4C1-glucopyranoside (4) and
3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol-2-O-(2',6'-di-O-galloyl)-beta-D
-4C1-glucopyranoside (7), and two C-glycosidic tannins,
vascalaginone (10) and grandininol (14), together with
fourteen known metabolites, gallic acid (1), methyl
gallate (2), nilocitin (3), 1-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-(alpha/beta)-D-glucopyranose
(5), 4,6-(S)-hexahydroxydiphenoyl-(alpha/beta)-D-glucopyranose
(6), 3,4,6-valoneoyl-(alpha/beta)-D-glucopyranose (8),
pedunculagin (9), casuariin (11), castalagin (12),
vascalagin (13), casuarinin (15), grandinin (16),
methyl-flavogallonate (17) and ellagic acid (18), were
identified from the leaves of Pimenta dioica (Merr.) L.
(Myrtaceae) on the basis of their chemical and
physicochemical analysis (UV, HRESI-MS, 1D and 2D NMR).
It was found that 9 is the most cytotoxic compound
against solid tumour cancer cells, the most potent
scavenger against the artificial radical DPPH and
physiological radicals including ROO*, OH*, and O2-*,
and strongly inhibited the NO generation and induced the
proliferation of T-lymphocytes and macrophages. On the
other hand, 3 was the strongest NO inhibitor and 16 the
highest stimulator for the proliferation of
T-lymphocytes, while 10 was the most active inducer of
macrophage proliferation.
Publication Types:
PMID: 17913067 [PubMed - indexed for MEDLINE]
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Ellagic acid prevents cisplatin-induced oxidative
stress in liver and heart tissue of rats.
Yüce A,
Ateşşahin A,
Ceribaşi AO,
Aksakal M.
Experimental Research Centre, Firat University Medical
School, Elaziğ, Turkey. ryuce@hotmail.com
Cisplatin is one of the most active cytotoxic agents in
the treatment of cancer. High doses of cisplatin have
also been known to produce hepatotoxicity, and several
studies suggest that supplemental antioxidants can
reduce cisplatin-induced hepatotoxicity. The present
study was designed to determine the effects on the liver
and heart oxidant/antioxidant system and the possible
protective effects of ellagic acid on liver and heart
toxicity induced by cisplatin. The control group
received 0.9% saline; animals in the ellagic acid group
received only ellagic acid (10 mg/kg); animals in the
cisplatin group received only cisplatin (7 mg/kg);
animals in cisplatin + ellagic acid group received
ellagic acid for 10 days after cisplatin. The rats were
killed at the end of the treatment period.
Malondialdehyde (MDA) and glutathione (GSH) levels,
glutathione-peroxidase (GSH-Px) and catalase (CAT)
activities were determined in liver and heart tissue.
While administration of cisplatin increased the MDA
levels in liver and heart tissues, it decreased the GSH,
GSH-Px and CAT in these samples when compared to the
control group. The administration of ellagic acid to
cisplatin-treated rats decreased the MDA levels, and
increased GSH, GSH-Px and CAT in these samples.
Cisplatin caused marked damages in the histopathological
status of liver and heart tissues. These damages were
ameliorated by ellagic acid administration. In
conclusion, ellagic acid may be used in combination with
cisplatin in chemotherapy to improve cisplatin-induced
oxidative stress parameters.
PMID: 17910619 [PubMed - indexed for MEDLINE]
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Utilization of acorn fringe for ellagic acid
production by Aspergillus oryzae and Endomyces fibuliger.
Huang W,
Li Z,
Niu H,
Li L,
Lin W,
Yang J.
Institute for Nanobiomedical Technology and Membrane
Biology, State Key Lab of Biotherapy of Human Diseases,
Cancer Center, West China Hospital, West China Medical
School, Sichuan University, Chengdu 610041, China.
huangwen@iee.pku.edu.cn
Conversion of acorn fringe extract into ellagic acid
production by Aspergillus oryzae and Endomyces fibuliger
were investigated. The results showed that ellagic acid
production was maximized when co-fermentation of the two
fungi was performed at 30 degrees C and pH 5.0 with 5.7
g/l of initial substrate concentration, which were close
to the optimal values for both fungi to yield an
appropriate consortium of hydrolytic enzymes. Meanwhile,
it was found that the co-fermentation could compensate
the deficiencies in the level of polyphenol oxidase
activity from pure A. oryzae and the levels of
ellagitannin acyl hydrolase and beta-glucosidase
activities from pure E. fibuliger, resulting in. 0.91
g/l of biomass concentration containing 1.84 g/l of
ellagic acid. The research not only demonstrates that
the co-fermentation is an effective approach to utilize
forest byproduct for ellagic acid production, but also
provides more evidences for understanding evolution of
ellagic acid production with enzymes actions, which is
important for process control of ellagic acid production
in industrial application.
Publication Types:
PMID: 17826988 [PubMed - indexed for MEDLINE]
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Pomegranate ellagitannin-derived metabolites inhibit
prostate cancer growth and localize to the mouse
prostate gland.
Seeram NP,
Aronson WJ,
Zhang Y,
Henning SM,
Moro A,
Lee RP,
Sartippour M,
Harris DM,
Rettig M,
Suchard MA,
Pantuck AJ,
Belldegrun A,
Heber D.
Center for Human Nutrition, Greater Los Angeles VA
Medical Center, Los Angeles, California, USA. nseeram@mednet.ucla.edu
Our group has shown in a phase II clinical trial that
pomegranate juice (PJ) increases prostate specific
antigen (PSA) doubling time in prostate cancer (CaP)
patients with a rising PSA. Ellagitannins (ETs) are the
most abundant polyphenols present in PJ and contribute
greatly towards its reported biological properties. On
consumption, ETs hydrolyze to release ellagic acid (EA),
which is then converted by gut microflora to
3,8-dihydroxy-6H-dibenzo[b, d]pyran-6-one (urolithin A,
UA) derivatives. Despite the accumulating knowledge of
ET metabolism in animals and humans, there is no
available data on the pharmacokinetics and tissue
disposition of urolithins. Using a standardized
ET-enriched pomegranate extract (PE), we sought to
further define the metabolism and tissue distribution of
ET metabolites. PE and UA (synthesized in our
laboratory) were administered to C57BL/6 wild-type male
mice, and metabolite levels in plasma and tissues were
determined over 24 h. ET metabolites were concentrated
at higher levels in mouse prostate, colon, and
intestinal tissues as compared to other tissues after
administration of PE or UA. We also evaluated the
effects of PE on CaP growth in severe combined
immunodeficient (SCID) mice injected subcutaneously with
human CaP cells (LAPC-4). PE significantly inhibited
LAPC-4 xenograft growth in SCID mice as compared to
vehicle control. Finally, EA and several synthesized
urolithins were shown to inhibit the growth of human CaP
cells in vitro. The chemopreventive potential of
pomegranate ETs and localization of their bioactive
metabolites in mouse prostate tissue suggest that
pomegranate may play a role in CaP treatment and
chemoprevention. This warrants future human tissue
bioavailability studies and further clinical studies in
men with CaP.
Publication Types:
PMID: 17722872 [PubMed - indexed for MEDLINE]
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Effect of non-alcoholic compounds of alcoholic drinks
on the pancreas.
Feick P,
Gerloff A,
Singer MV.
Department of Medicine II (Gastroenterology, Hepatology
and Infectious Diseases), University Hospital of
Heidelberg at Mannheim, Mannheim, Germany.
Over the past 30 years the role of alcohol (ethanol) in
the development of acute and chronic pancreatitis has
been intensively investigated. However, ethanol is
generally consumed in form of alcoholic beverages which
contain numerous non-alcoholic compounds. At least on
gastric acid secretion it has been convincingly
demonstrated that alcohol and alcoholic beverages have
markedly different effects. In the present article, we
provide an overview about the effect of different
non-alcoholic constituents of alcoholic beverages on the
pancreas and their possible interaction with molecular
mechanisms leading to 'alcoholic' pancreatitis. The
present data indicate that pancreatic enzyme secretion
in humans is stimulated by non-alcoholic constituents of
beer which are generated by alcoholic fermentation of
glucose. In addition, it has been shown that natural
phenolic compounds (e.g. quercetin, resveratrol) of
alcoholic beverages exert different effects on the
pancreasin vitro, such as inhibition of pancreatic
enzyme output, of pancreatic stellate cell activation
and of pancreatic cancer growth as well as protective
effects against oxidative stress and on experimental
induced acute pancreatitis in rats. However, it should
be pointed out that alcoholic beverages contain much
more non-alcoholic ingredients. Since the effects of
these are still unknown, caution is required in
attempting to define alcoholic etiology of pancreatitis
without considering the effect of non-alcoholic
compounds of alcoholic beverages. (c) 2007 S. Karger AG,
Basel and IAP.
Publication Types:
PMID: 17592224 [PubMed - indexed for MEDLINE]
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Effects of various plant polyphenols on bladder
carcinogen benzidine-induced mutagenicity.
Makena PS,
Chung KT.
Department of Biology, The University of Memphis, TN
38152, United States. spmakena@gmail.com
Benzidine (Bz), a human bladder carcinogen, was strongly
mutagenic to Salmonella TA102 tester strain in the Ames
Salmonella microsome/mutagenicity assay in the presence
of rat liver S9 mix. Various non-mutagenic plant
polyphenols were included in the assay to test their
inhibitory effects on the Bz-induced mutations.
Coumestrol, ellagic acid (EA), (-)-epicatechin (EC),
(-)-epichatechingallate (ECG), gallic acid (GA), (-)-gallocatechin
(GC), plumbagin, propyl gallate (PG), taxifolin, and
2,2',4'-trihydroxychalcone were found to have a strong
inhibitory effect on Bz-induced mutations. (-)-Epigallo-catechingallate
(EGCG), fisetin, (-)-gallocatechingallate (GCG), and
piceatannol were moderately inhibitory to the mutations;
whereas, (-)-catechin, (-)-catechingallate (CG), and
reseveratrol were weakly inhibitory to the mutations.
(-)-Epigallocatechin (EGC) and 7,3',4'-trihydroxy
isoflavon were not inhibitory to the Bz-induced
mutations. Isoliquirtigenin, quercetin dihydrate, and
rhein were found to be mutagenic in tester strain TA102.
Benzidine mediated lipid peroxidation was conducted
employing the thiobarbituric acid reactive substances (TBARS)
assay using linoleic acid as a substrate. In the
presence of rat liver S9 mix, Bz could cause lipid
peroxidation as an outcome of production of oxygen free
radicals. Incorporation of the above mentioned
non-mutagenic plant polyphenols significantly inhibited
benzidine mediated lipid peroxidation in a time
dependent manner. These polyphenols also effectively
reduced the iron mediated lipid peroxidation. Thus, it
is concluded that the inhibition of oxidative
mutagenicity of Bz by plant polyphenols could be due to
an inhibitory effect of plant polyphenols on the
bioactivating enzymes such as cytochrome P-450 and
peroxidase and the chelation of iron present in the
cytochrome P-450 in the S9 mix. Thus, these plant
polyphenols play a significant inhibitory role on Bz-induced
mutagenicity.
Publication Types:
PMID: 17560706 [PubMed - indexed for MEDLINE]
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Ellagic acid from acorn fringe by enzymatic
hydrolysis and combined effects of operational variables
and enzymes on yield of the production.
Huang W,
Niu H,
Li Z,
Li L,
Wang W.
Institute for Nanobiomedical Technology and Membrane
Biology, State Key Laboratory of Biotherapy of Human
Diseases, Cancer Center, West China Hospital, West China
Medical School, Sichuan University, Gaoxinqu, Chengdu,
China. huangwen@iee.pku.edu.cn
The individual effects of three different enzyme types
-- one single enzyme (ellagitannin acyl hydrolase) and
two combinations of enzymes (ellagitannin acyl
hydrolase-beta-glucosidase-polyphenol oxidase and
ellagitannin acyl hydrolase-cellulase-xylanase) -- on
ellagic acid yield, combined with other process
parameters -- enzyme concentration, hydrolysis time,
particle size and solid-to-liquid ratio -- were
evaluated by response surface methodology. The selection
of the enzymes for the study was based on preliminary
experiments that showed higher increments in ellagic
acid yield. The quantitative parameters studied were
enzyme concentration (0.1, 0.45, 2 w/w or %),
solid-to-liquid ratio (0.05, 0.15, 0.2), particle size
(220, 445, 900 microm) and hydrolysis time (60, 89, 132
min). Experimental data for ellagic acid yield obtained
with a single enzyme and two combination enzymes
correlated very well with process parameters (P<0.0001),
resulting in models with high coefficient of
determination for ellagic acid yield (r(2)=0.9636). The
combinations of enzymes appeared more effective for
ellagic acid production than the single enzyme did. The
yield of ellagic acid from non-heat-treated acorn fringe
by the use of enzymes in general increased, compared
with that from heat-treated material. The research opens
a technological-efficient way and develop
easily-available renewable raw material for ellagic acid
production.
Publication Types:
PMID: 17544268 [PubMed - indexed for MEDLINE]
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Individual and combined effects of physicochemical
parameters on ellagitannin acyl hydrolase and ellagic
acid production from ellagitannin by Aspergillus oryzae.
Huang W,
Niu H,
Gong GH,
Lu YR,
Li ZS,
Li H.
Institute for Nanobiomedical Technology and Membrane
Biology, State Key Lab of Biotherapy of Human Diseases,
Cancer Center, West China Hospital, West China Medical
School, Sichuan University, Keyuan 4 Road No.1, Gaopeng
Avenue, Chengdu, Gaoxin District, 610041, China.
The individual and interactive effects of
physicochemical parameters on ellagitannin acyl
hydrolase activity and ellagic acid production by
Aspergillus oryzae using ellagitannins from acorn fringe
of oak as substrate were studied. Ellagitannins
concentration, incubation time were identified as
important physicochemical parameters influencing the
enzyme synthesis and the production accumulation, and
the substrate concentration with initial pH was
determined to has an interactive effect on the enzyme
synthesis, while ellagitannins concentration and initial
pH with incubation time were found to have interactions
on the production accumulation. Furthermore, the
parameters were optimized by quadratic programming.
Under optimum condition, the fermentation run lasted 84
h with 4 g L(-1 )ellagitannins concentration, yielding
17.7% ellagic acid. However, the maximum enzyme activity
was obtained in 96 h with 5 g L(-1 )substrate
concentration. The research demonstrated a possible way
to develop an efficient approach for recovery of higher
added-value product (ellagic acid) from forestry
byproduct (acorn fringe of oak).
PMID: 17450459 [PubMed - as supplied by publisher]
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Impact of antioxidant supplementation on
chemotherapeutic efficacy: a systematic review of the
evidence from randomized controlled trials.
Block KI,
Koch AC,
Mead MN,
Tothy PK,
Newman RA,
Gyllenhaal C.
Institute for Integrative Cancer Research and Education,
1800 Sherman Avenue, Suite 350, Evanston, IL 60201, USA.
kblock@blockmedical.com
PURPOSE: Much debate has arisen about whether
antioxidant supplementation alters the efficacy of
cancer chemotherapy. Some have argued that antioxidants
scavenge the reactive oxygen species integral to the
activity of certain chemotherapy drugs, thereby
diminishing treatment efficacy. Others suggest
antioxidants may mitigate toxicity and thus allow for
uninterrupted treatment schedules and a reduced need for
lowering chemotherapy doses. The objective of this study
is to systematically review the literature in order to
compile results from randomized trials that evaluate
concurrent use of antioxidants with chemotherapy.
DESIGN: MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch
and EMBASE databases were searched. Only randomized,
controlled clinical trials that reported survival and/or
tumor response were included in the final tally. The
literature searches were performed in duplicate
following a standardized protocol. No meta-analysis was
performed due to heterogeneity of tumor types and
treatment protocols used in trials that met the
inclusion criteria. RESULTS: Of 845 articles considered,
19 trials met the inclusion criteria. Antioxidants
evaluated were: glutathione (7), melatonin (4), vitamin
A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine
(1), vitamin E (1) and ellagic acid (1). Subjects of
most studies had advanced or relapsed disease.
CONCLUSION: None of the trials reported evidence of
significant decreases in efficacy from antioxidant
supplementation during chemotherapy. Many of the studies
indicated that antioxidant supplementation resulted in
either increased survival times, increased tumor
responses, or both, as well as fewer toxicities than
controls; however, lack of adequate statistical power
was a consistent limitation. Large, well-designed
studies of antioxidant supplementation concurrent with
chemotherapy are warranted.
Publication Types:
PMID: 17367938 [PubMed - indexed for MEDLINE]
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Effect of storage conditions on the biological
activity of phenolic compounds of blueberry extract
packed in glass bottles.
Srivastava A,
Akoh CC,
Yi W,
Fischer J,
Krewer G.
Department of Food Science and Technology, University of
Georgia, Athens, GA 30602-7610, USA.
Recent research suggests that blueberries are rich in
total polyphenols and total anthocyanins. Phenolic
compounds are highly unstable and may be lost during
processing, particularly when heat treatment is
involved. There is no systematic study available
providing information on the fate of phenolic compounds
during storage and how that affects their biological
activity. We provide a systematic evaluation of the
changes observed in total polyphenols (TPP), total
anthocyanins (TACY), Trolox equivalent antioxidant
capacity (TEAC), phenolic acids, and individual
anthocyanins of blueberry extract stored in glass
bottles and the ability of blueberry extract to inhibit
cell proliferation. The extract was stored at different
temperatures (-20 +/- 1, 6 +/- 1, 23 +/- 1, and 35 +/- 1
degrees C). Two cultivars, Tifblue and Powderblue, were
chosen for the study. The recoveries of TPP, TACY, and
TEAC in blueberry extract after pressing and heating
were approximately 25, approximately 29, and
approximately 69%, respectively, for both cultivars. The
recovery of gallic acid, catechin, and quercetin was
approximately 25%. Ferulic acid was not detected in the
final extract in both Tifblue and Powderblue cultivars.
The recovery of peonidin, malvidin, and cyanidin
glycosides was approximately 20% in the final extract in
both cultivars. Losses due to storage were less when
compared with initial losses due to processing. At -20
degrees C, no statistically significant loss of TPP,
TACY, and TEAC was observed up to 30 days (P < 0.05). At
6 degrees C storage, there was a significant loss
observed from 15 to 30 days. Similar results were
obtained at 23 and 35 degrees C (P < 0.05). There was
retention of more than 40% of ellagic and quercetin
after 60 days at 35 +/- 1 degrees C. Anthocyanins were
not detected after 60 days of storage at 35 +/- 1
degrees C. Significant retention (P < 0.05) was obtained
for malvidin (42.8 and 25.8%) and peonidin (74.0 and
79.5%) after 60 days of storage at 23 +/- 1 degrees C in
glass bottles for Tifblue and Powderblue, respectively,
when compared with other individual anthocyanins. A
linear relationship was observed between TEAC values and
total polyphenols or total anthocyanins. A cell
viability assay was performed using HT-29 cancer cell
lines and anthocyanins extracted from 30, 60, and 90
days of stored extract at 6 +/- 1 and 23 +/- 1 degrees
C. A significant cell proliferation inhibition
percentage was observed in 30 days, although this was
reduced significantly after 30-90 days. These results
suggest that heating and storage conditions
significantly affect the phenolic compounds and their
biological activities. Frozen and low temperature
storage are suggested for blueberry extract in order to
retain the bioactive components.
Publication Types:
PMID: 17348670 [PubMed - indexed for MEDLINE]
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Antiproliferative activity is predominantly
associated with ellagitannins in raspberry extracts.
Ross HA,
McDougall GJ,
Stewart D.
Quality, Health and Nutrition Programme, Genes to
Products Theme, Scottish Crop Research Institute,
Invergowrie, Dundee DD2 5DA, UK.
Raspberry extracts enriched in polyphenols, but devoid
of organic acids, sugars and vitamin C, were prepared by
sorption to C18 solid phase extraction matrices and
tested for their ability to inhibit the proliferation of
human cervical cancer (HeLa) cells in vitro. The
raspberry extract reduced proliferation in a
dose-dependent manner whether this was judged by cell
number or measurements of cell viability. However,
measurements based on cell viability were more accurate
and gave an EC(50) value of 17.5 microg/ml gallic acid
equivalents (GAE) at day 4 of culture. Raspberry
extracts were fractionated by sorption to Sephadex LH-20
into an unbound fraction, which was obviously enriched
in anthocyanins, and a bound fraction. The unbound
anthocyanin-enriched fraction was much less effective in
reducing proliferation then the original extract and
gave an EC(50) value estimated at 67 microg/ml. The
LH-20 bound fraction was more effective than the
original raspberry extract (EC(50)=13 microg/ml)
suggesting that the main anti-proliferative agents were
retained in the bound fraction. Analysis of the original
extract, the unbound and the LH20 bound fractions by
LC-MS confirmed that the unbound fraction was enriched
in anthocyanins and the bound fraction primarily
contained ellagitannins. The ellagitannin-rich bound
fraction had the highest antioxidant capacity as
measured by the ferric reducing antioxidant potential
(FRAP) assay. The mechanism by which the ellagitannins
inhibit proliferation of cancer cells is discussed.
PMID: 17126865 [PubMed - indexed for MEDLINE]
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Antioxidant and apoptosis-inducing activities of
ellagic acid.
Han DH,
Lee MJ,
Kim JH.
Department of Biochemistry, College of Dentistry, Kyung
Hee University, Seoul 130-701, Korea.
BACKGROUND: Antioxidant, antiproliferative and apoptosis
inducing activities of a natural polyphenolic compound,
ellagic acid, were studied. MATERIALS AND METHODS: DPPH
radical scavenging and lipid peroxidation inhibitory
activities were observed. Activities of antioxidant
enzymes, superoxide dismutase (SOD), catalase (CAT) and
glutathione peroxidase (GPX) were measured in ellagic
acid-treated V79-4 cells. For apoptotic inducing
activity, human osteogenic sarcoma (HOS) cell
proliferation, chromosomal DNA degradation and changes
in apoptosis-related protein levels were measured.
RESULTS: Ellagic acid showed high DPPH radical
scavenging and lipid peroxidation inhibition activities.
SOD, CAT and GPX activities were significantly increased
in ellagic acid-treated V79-4 cells. Ellagic acid
significantly reduced HOS cell proliferation, and
induced apoptosis evidenced by chromosomal DNA
degradation and apoptotic body appearance. Bax
expression was induced and caspase-3 was activated by
ellagic acid treatment. CONCLUSION: Ellagic acid
exhibited both antioxidant activity in V79-4 cells and
apoptosis-inducing activity in HOS cells through the
up-regulation of Bax and activation of caspase-3.
Publication Types:
PMID: 17094489 [PubMed - indexed for MEDLINE]
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Isolation, purification and identification of ellagic
acid derivatives, catechins, and procyanidins from the
root bark of Anisophyllea dichostyla R. Br.
Khallouki F,
Haubner R,
Hull WE,
Erben G,
Spiegelhalder B,
Bartsch H,
Owen RW.
Division of Toxicology and Cancer Risk Factors, German
Cancer Research Center (DKFZ), Im Neuenheimer Feld 280,
D-69120 Heidelberg, Germany.
The root bark of Anisophyllea dichostyla R. Br. is
traditionally used in the Democratic Republic Congo for
the treatment of several conditions such as anorexia,
fatigue and intestinal infections. We have identified
and quantitated several polyphenol antioxidants in the
methanol extract of the root bark (120g). The polyphenol
content (3.32g/kg) was predominantly ellagitannins (25%)
and polyhydroxyflavan-3-ols (catechins and procyanidins,
75%) with 3'-O-methyl-3,4-methylenedioxo ellagic acid
4'-O-beta-d-glucopyranoside and (-)-epicatechin as the
major species in each class. These two compounds and the
following species were identified unequivocally by NMR
spectroscopy: (+)-catechin, (-)-epicatechin 3-O-gallate,
3-O-methyl ellagic acid, 3,3'-di-O-methyl ellagic acid,
3'-O-methyl-3,4-methylenedioxo ellagic acid,
3'-O-methyl-3,4-methylenedioxo ellagic acid
4'-O-beta-d-glucopyranoside, and 3'-O-methyl ellagic
acid 4-O-beta-d-xylopyranoside. The following additional
compounds were purified by semi-preparative HPLC and
tentatively identified on the basis of UV spectra,
HPLC-ESI-MS and nano-ESI-MS-MS:
(+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin
(procyanidin B(1)), epicatechin-(4beta-->8)-epicatechin
(procyanidin B(2)), an (epi)catechin trimer, 3-O-methyl
ellagic acid 4-O-beta-d-glucopyranoside, (-)-epicatechin
3-O-vanillate, 3,4-methylenedioxo ellagic acid 4'-O-
beta-d-glucopyranoside, and 3,3'-di-O-methyl ellagic
acid 4-O-beta-d-xylopyranoside. Fractionation of the raw
extract by column chromatography on silicic acid yielded
10 fractions. In the hypoxanthine/xanthine oxidase
antioxidant assay system, CC-9 which contained a range
of polyphenols dominated by (-)-epicatechin-O-gallate
proved to be the most potent antioxidant fraction
(IC(50)=52 micro g/mL) in terms of ROS scavenging. In
terms of XO inhibition CC-8, dominated by (epi)catechin
trimer and which also contained appreciable amounts of
3'-O-methyl ellagic acid 4'-O-beta-d-xylopyranoside, as
well as the catechins
(+)-catechin-3-O-beta-d-glucopyranoside, epicatechin-(4beta-->8)-catechin
(procyanidin B(1)), and (-)-epicatechin 3-O-gallate,
proved to be the most potent (IC(50)=36 micro g/mL).
PMID: 17084499 [PubMed - indexed for MEDLINE]
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