X-Message-Number: 26085
Date: Mon, 25 Apr 2005 05:30:16 -0700 (PDT)
From: Doug Skrecky <>
Subject: possible health consequences of pomegranate juice

[Warning: Pomegranate juice may inhibit atherosclerosis, reduce
blood pressure, limit stroke damage, prevent various cancers,
accelerate wound healing, improve mood, and strengthen bones.
Drink at your own risk.]

[50 ml/day of pomegranate juice was consumed in the 3 year study
listed below.]

Clin Nutr. 2004 Jun;23(3):423-33.
Pomegranate juice consumption for 3 years by patients with
carotid artery stenosis reduces common carotid intima-media
thickness, blood pressure and LDL oxidation.
  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.

Atherosclerosis. 2001 Sep;158(1):195-8.
Pomegranate juice consumption inhibits serum angiotensin
converting enzyme activity and reduces systolic blood pressure.
  Consumption of pomegranate juice which is rich in tannins,
possess anti-atherosclerotic properties which could be related to
its potent anti-oxidative characteristics. As some antioxidants
were recently shown to reduce blood pressure, we studied the
effect of pomegranate juice consumption (50 ml, 1.5mmol of total
polyphenols per day, for 2 weeks) by hypertensive patients on
their blood pressure and on serum angiotensin converting enzyme
(ACE) activity. A 36% decrement in serum ACE activity and a 5%
reduction in systolic blood pressure were noted. Similar
dose-dependent inhibitory effect (31%) of pomegranate juice on
serum ACE activity was observed also in vitro. As reduction in
serum ACE activity, even with no decrement in blood pressure,
was previously shown to attenuate atherosclerosis, pomegranate
juice can offer a wide protection against cardiovascular diseases
which could be related to its inhibitory effect on oxidative
stress and on serum ACE activity.

Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4896-901.
Epub 2005 Mar 21.
Beneficial effects of pomegranate juice on oxidation-sensitive
genes and endothelial nitric oxide synthase activity at sites of
perturbed shear stress.
  Atherosclerosis is enhanced in arterial segments exposed to
disturbed flow. Perturbed shear stress increases the expression
of oxidation-sensitive responsive genes (such as ELK-1 and p-JUN)
in the endothelium. Evidence suggests that polyphenolic
antioxidants contained in the juice derived from the pomegranate
can contribute to the reduction of oxidative stress and
atherogenesis. The aim of the present study was to evaluate the
effects of intervention with pomegranate juice (PJ) on
oxidation-sensitive genes and endothelial NO synthase (eNOS)
expression induced by high shear stress in vitro and in vivo.
Cultured human coronary artery endothelial cells (EC) exposed to
high shear stress in vitro and hypercholesterolemic mice were
used in this study. PJ concentrate reduced the activation of
redox-sensitive genes (ELK-1 and p-JUN) and increased eNOS
expression (which was decreased by perturbed shear stress) in
cultured EC and in atherosclerosis-prone areas of
hypercholesterolemic mice. Moreover, oral administration of PJ
to hypercholesterolemic mice at various stages of disease
reduced significantly the progression of atherosclerosis. This
experimental study indicates that the proatherogenic effects
induced by perturbed shear stress can be reversed by chronic
administration of PJ. This approach may have implications for
the prevention or treatment of atherosclerosis and its clinical

Zhonghua Yu Fang Yi Xue Za Zhi. 2005 Mar;39(2):80-3.
Intervention of antioxidant system function of aged rats by
giving fruit juices with different antioxidant capacities.
  OBJECTIVE: To observe the effects of fruit juices with
different antioxidant capacity on antioxidant system function
of aged rats. METHODS: Thirty Wistar rats were randomly divided
into three groups: pomegranate juice and apple juice as two
experimental groups, while distilled water as normal control
group. They were administrated fruit juices or distilled water
respectively by gavage daily for 4 weeks. At the end of
experiment, the antioxidant system function was assessed.
RESULTS: The aged rats in pomegranate juice group showed
significantly higher serum antioxidant capacity (0.90 +/- 0.13)
mmol/L than that in control group (0.79 +/- 0.10) mmol/L
(P < 0.05). The concentrations of serum carbonyl and oxLDL were
decreased significantly in pomegranate juice group as compared
to the control group (P < 0.05). The percentage of injured blood
lymphocyte DNA and the ratio of tail length/total length were
declined significantly in pomegranate juice group (P < 0.05 and
P < 0.01 respectively). The apple juice showed no effects except
decreased ratio of tail length/total length of injured
lymphocyte DNA. There were no changes in concentrations of serum
vitamin C, vitamin E, urinary 8-OH-dG excretion and the
activities of serum SOD, GSH-Px, CAT among three groups.
CONCLUSIONS: The pomegranate juice should possess higher
antioxidant capacity and might improve the antioxidant system
function of aged rats, while the apple juice is relatively lower
in antioxidant capacity and not very effective. The polyphenols
in pomegranate juice might be the important functional components.

Pediatr Res. 2005 Mar 17; [Epub ahead of print]
Maternal Dietary Supplementation with Pomegranate Juice Is
Neuroprotective in an Animal Model of Neonatal Hypoxic-Ischemic
Brain Injury.
  Neonatal hypoxic-ischemic brain injury remains a significant
cause of morbidity and mortality and lacks effective therapies for
prevention and treatment. Recently, interest in the biology of
polyphenol compounds has led to the discovery that dietary
supplementation with foods rich in polyphenols (e.g. blueberries,
green tea extract) provides neuroprotection in adult animal
models of ischemia and Alzheimer's disease. We sought to determine
whether protection of the neonatal brain against a
hypoxic-ischemic insult could be attained through supplementation
of the maternal diet with pomegranate juice, notable for its high
polyphenol content. Mouse dams were provided ad libitum access to
drinking water with pomegranate juice, at one of three doses, as
well as plain water, sugar water, and vitamin C water controls
during the last third of pregnancy and throughout the duration of
litter suckling. At postnatal day 7, pups underwent unilateral
carotid ligation followed by exposure to 8% oxygen for 45 min.
Brain injury was assessed histologically after 1 wk (percentage of
tissue area loss) and biochemically after 24 h (caspase-3 activity).
Dietary supplementation with pomegranate juice resulted in markedly
decreased brain tissue loss (>60%) in all three brain regions
assessed, with the highest pomegranate juice dose having greatest
significance (p </= 0.0001). Pomegranate juice also diminished
caspase-3 activation by 84% in the hippocampus and 64% in the
cortex. Ellagic acid, a polyphenolic component in pomegranate juice,
was detected in plasma from treated but not control pups. These
results demonstrate that maternal dietary supplementation with
pomegranate juice is neuroprotective for the neonatal brain.

Invest New Drugs. 2005 Mar;23(2):121-2.
Pomegranate (Punica granatum) pure chemicals show possible
synergistic inhibition of human PC-3 prostate cancer cell invasion
across Matrigel.
  Four pure chemicals, ellagic acid (E), caffeic acid (C), luteolin
(L) and punicic acid (P), all important components of the aqueous
compartments or oily compartment of pomegranate fruit (Punica
granatum), and each belonging to different representative chemical
classes and showing known anticancer activities, were tested as
potential inhibitors of in vitro invasion of human PC-3 prostate
cancer cells in an assay employing Matrigel artificial membranes.
All compounds significantly inhibited invasion when employed
individually. When C, P, and L were equally combined at the same
gross dosage (4 microg/ml) as when the compounds were tested
individually, a supradditive inhibition of invasion was observed,
measured by the Kruskal-Wallis non-parametric test.

Eur J Cancer Prev. 2004 Aug;13(4):345-8.
Breast cancer chemopreventive properties of pomegranate (Punica
granatum) fruit extracts in a mouse mammary organ culture.
  We previously reported anticancer effects of pomegranate
extracts in human breast cancer cells in vitro and also
chemopreventive activity of pomegranate fermented juice
polyphenols (W) in a mouse mammary organ culture (MMOC). In the
present study we decided to expand the MMOC investigations to
also include an evaluation of the potential chemopreventive
efficacy of a purified chromatographic peak of W (Peak B), and
also of whole pomegranate seed oil. In brief, an MMOC was
established according to a known method. For the first 10 days of
culture, the glands were treated with pomegranate fermented juice
polyphenols (W), a high-performance liquid chromatographic (HPLC)
peak separated from W (peak B), or pomegranate seed oil (Oil, and
on day 3, exposed to the carcinogen 7,12-dimethylbenz[a]anthracene
(DMBA), and for 10 days treated with the putative pomegranate
chemopreventive. The glands were subsequently harvested and
tumours counted by visual inspection. While W effected a 42%
reduction in the number of lesions compared with control, peak B
and pomegranate seed oil each effected an 87% reduction. The
results highlight enhanced breast cancer preventive potential both
for the purified compound peak B and for pomegranate seed oil,
both greater than that previously reported for pomegranate
fermented juice polyphenols.

Int J Cancer. 2005 Jan 20;113(3):423-33.
Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract
modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis
in CD-1 mice.
  Chemoprevention has come of age as an effective cancer control
modality; however, the search for novel agent(s) for the
armamentarium of cancer chemoprevention continues. We argue that
agents capable of intervening at more than one critical pathway in
the carcinogenesis process will have greater advantage over other
single-target agents. Pomegranate fruit extract (PFE) derived from
the tree Punica granatum possesses strong antioxidant and
antiinflammatory properties. Pomegranate fruit was extracted with
acetone and analyzed based on matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry and found to
contain anthocyanins, ellagitannins and hydrolyzable tannins. We
evaluated whether PFE possesses antitumor-promoting effects. We
first determined the effect of topical application of PFE to CD-1
mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
conventional markers and other novel markers of skin tumor promotion.
We found that topical application of PFE (2 mg/mouse) 30 min prior to
TPA (3.2 nmole/mouse) application on mouse skin afforded significant
inhibition, in a time-dependent manner, against TPA-mediated increase
in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC)
activity and protein expression of ODC and cyclooxygenase-2. We also
found that topical application of PFE resulted in inhibition of
TPA-induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as
activation of NF-kappaB and IKKalpha and phosphorylation and
degradation of IkappaBalpha. We next assessed the effect of skin
application of PFE on TPA-induced skin tumor promotion in
7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse. The animals
pretreated with PFE showed substantially reduced tumor incidence and
lower tumor body burden when assessed as total number of tumors per
group, percent of mice with tumors and number of tumors per animal as
compared to animals that did not receive PFE. In TPA-treated group,
100% of the mice developed tumors at 16 weeks on test, whereas at this
time in PFE-treated group, only 30% mice exhibited tumors. Skin
application of PFE prior to TPA application also resulted in a
significant delay in latency period from 9 to 14 weeks and afforded
protection when tumor data were considered in terms of tumor incidence
and tumor multiplicity. The results of our study provide clear evidence
that PFE possesses antiskin-tumor-promoting effects in CD-1 mouse.
Because PFE is capable of inhibiting conventional as well as novel
biomarkers of TPA-induced tumor promotion, it may possess
chemopreventive activity in a wide range of tumor models. Thus, an
in-depth study to define active agent(s) in PFE capable of affording
antitumor-promoting effect is warranted.

J Med Food. 2004 Summer;7(2):256-9.
Study on wound healing activity of Punica granatum peel.
  The methanolic extract of dried pomegranate (Punica granatum)
peels showed the presence of a high content of phenolic compounds
(44.0%) along with other constituents. This extract was formulated
as a 10% (wt/wt) water-soluble gel and was studied for its wound
healing property against an excision wound on the skin of Wistar
rats. The activity was compared with that of a commercial topical
antibacterial applicant. The wound healing activity was assessed by
measuring the percent contraction in skin and estimation of collagen
content in terms of hydroxyproline content. Healed skin was also
subjected to histopathological studies to examine the microscopic
changes. The animals treated with 2.5% gel showed moderate healing
(55.8% and 40.8% healing compared with negative and positive
controls, respectively), whereas the group treated with 5.0% gel
showed good healing (59.5% and 44.5% healing compared with negative
and positive controls, respectively). The amount of hydroxyproline
increased by twofold in the group treated with 5.0% gel.
Histopathological studies also supported the wound healing on
application of the gels. The group of rats that received 5.0% gel
showed complete healing after 10 days, whereas in rats treated with
2.5% gel, healing was observed on day 12, in contrast to the
positive control animals receiving the blank gel, which took 16-18
days for complete healing. The results of this study may be extended
to different types of wounds so that the formulation could be
exploited to develop it as a topical dermatological formulation.
High-performance liquid chromatography analysis of the extract
showed the presence of gallic acid and catechin as major components.

J Ethnopharmacol. 2004 May;92(1):93-101.
Pomegranate extract improves a depressive state and bone properties
in menopausal syndrome model ovariectomized mice.
  Pomegranate is known to contain estrogens (estradiol, estrone, and
estriol) and show estrogenic activities in mice. In this study, we
investigated whether pomegranate extract is effective on experimental
menopausal syndrome in ovariectomized mice. Prolongation of the
immobility time in forced swimming test, an index of depression, was
measured 14 days after ovariectomy. The bone mineral density (BMD)
of the tibia was measured by X-ray absorptiometry and the structure
and metabolism of bone were also analyzed by bone histomorphometry.
Administration of pomegranate extract (juice and seed extract) for 2
weeks to ovariectomized mice prevented the loss of uterus weight and
shortened the immobility time compared with 5% glucose-dosed mice
(control). In addition, ovariectomy-induced decrease of BMD was
normalized by administration of the pomegranate extract. The bone
volume and the trabecular number were significantly increased and
the trabecular separation was decreased in the pomegranate-dosed
group compared with the control group. Some histological bone
formation/resorption parameters were significantly increased by
ovariectomy but were normalized by administration of the pomegranate
extract. These changes suggest that the pomegranate extract inhibits
ovariectomy-stimulated bone turnover. It is thus conceivable that
pomegranate is clinically effective on a depressive state and bone
loss in menopausal syndrome in women.

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