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Therapeutic Applications of Pomegranate (Punica granatum L.): A Review


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The pomegranate, Punica granatum L., is an ancient, mystical, unique fruit borne on a small, long-living tree cultivated throughout the Mediterranean region, as far north as the Himalayas, in Southeast Asia, and in California and Arizona in the United States. In addition to its ancient historical uses, pomegranate is used in several systems of medicine for a variety of ailments. The synergistic action of the pomegranate constituents appears to be superior to that of single constituents. In the past decade, numerous studies on the antioxidant, anticarcinogenic, and anti-inflammatory properties of pomegranate constituents have been published, focusing on treatment and prevention of cancer, cardiovascular disease, diabetes, dental conditions, erectile dysfunction, bacterial infections and antibiotic resistance, and ultraviolet radiation-induced skin damage. Other potential applications include infant brain ischemia, male infertility, Alzheimer's disease, arthritis, and obesity.
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Copyright © 2008 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 13, Number 2 June 2008
Alternative Medicine Review Volume 13, Number 2 2008
Review Article
Page 128
Julie Jurenka, MT (ASCP) – Associate Editor, Alternative Medicine Review;
technical assistant, Thorne Research
Correspondence address: Thorne Research, PO Box 25, Dover, ID 83825
The pomegranate, Punica granatum L., is an ancient, mystical,
unique fruit borne on a small, long-living tree cultivated throughout
the Mediterranean region, as far north as the Himalayas, in
Southeast Asia, and in California and Arizona in the United
States. In addition to its ancient historical uses, pomegranate
is used in several systems of medicine for a variety of ailments.
The synergistic action of the pomegranate constituents appears
to be superior to that of single constituents. In the past decade,
numerous studies on the antioxidant, anticarcinogenic, and
anti-inflammatory properties of pomegranate constituents
have been published, focusing on treatment and prevention
of cancer, cardiovascular disease, diabetes, dental conditions,
erectile dysfunction, bacterial infections and antibiotic
resistance, and ultraviolet radiation-induced skin damage.
Other potential applications include infant brain ischemia,
male infertility, Alzheimer’s disease, arthritis, and obesity.
(Altern Med Rev 2008;13(2):128-144)
e pomegranate, Punica granatum L., an an-
cient, mystical, and highly distinctive fruit, is the pre-
dominant member of two species comprising the Pu-
nicaceae family. It was lauded in ancient times in the
Old Testament of the Bible, the Jewish Torah, and the
Babylonian Talmud as a sacred fruit conferring powers
of fertility, abundance, and good luck. It also features
prominently in the ceremonies, art, and mythology of
the Egyptians and Greeks and was the personal emblem
of the Holy Roman Emperor, Maximilian. Pomegranate
is the symbol and heraldic device of the ancient city of
Granada in Spain from which the city gets its name.
erapeutic Applications of
Pomegranate (Punica granatum L.):
A Review
Julie Jurenka, MT (ASCP)
e genus name, Punica, was the Roman name for
Carthage, where the best pomegranates were known to
grow. Pomegranate is known by the French as grenade,
the Spanish as granada, and literally translates to seeded
(“granatus”) apple (“pomum”).
e pomegranate tree typically grows 12-16
feet, has many spiny branches, and can be extremely long
lived, as evidenced by trees at Versailles, France, known
to be over 200 years old. e leaves are glossy and lance-
shaped, and the bark of the tree turns gray as the tree
ages. e flowers are large, red, white, or variegated and
have a tubular calyx that eventually becomes the fruit.
e ripe pomegranate fruit can be up to five inches wide
with a deep red, leathery skin, is grenade-shaped, and
crowned by the pointed calyx. e fruit contains many
seeds (arils) separated by white, membranous pericarp,
and each is surrounded by small amounts of tart, red
juice. e pomegranate is native from the Himalayas
in northern India to Iran but has been cultivated and
naturalized since ancient times over the entire Mediter-
ranean region. It is also found in India and more arid
regions of Southeast Asia, the East Indies, and tropical
Africa. e tree is also cultivated for its fruit in the drier
regions of California and Arizona.
In addition to its ancient historical uses, pome-
granate is used in several systems of medicine for a vari-
ety of ailments. In Ayurvedic medicine the pomegranate
is considered a pharmacy unto itself and is used as an
antiparasitic agent,
a blood tonic,
and to heal aph-
thae, diarrhea, and ulcers.
Pomegranate also serves as
Copyright © 2008 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 13, Number 2 June 2008
Alternative Medicine Review Volume 13, Number 2 2008
Review Article
Page 129
a remedy for diabetes in the Unani system of medicine
practiced in the Middle East and India.
e current
explosion of interest in pomegranate as a medicinal and
nutritional product is evidenced by a MedLine search
from 2000 to present, revealing over 130 new scientific
papers pertaining to its health effects. Between 1950 and
1999 only 25 such publications appear on MedLine.
e potential therapeutic properties of pomegranate
are wide-ranging and include treatment and prevention
of cancer, cardiovascular disease, diabetes, dental con-
ditions, erectile dysfunction, and protection from ul-
traviolet (UV) radiation. Other potential applications
include infant brain ischemia, Alzheimer’s disease, male
infertility, arthritis, and obesity.
e following abbreviations for various pome-
granate extracts will be used throughout the article:
Pomegranate juice – PJ Â
Pomegranate by-product – PBP Â
Fermented pomegranate juice – FPJ Â
Cold-pressed seed oil – CPSO Â
Pomegranate peel extract – PPE Â
Pomegranate pulp juice – PPJ Â
Pomegranate fruit extract – PFE Â
Pomegranate flower extract – PFLE Â
Hydroalcoholic extract of pomegranate – HAEP Â
Gel-based pomegranate extract – GPBE Â
Biochemical Constituents
Over the past decade, significant progress has
been made in establishing the pharmacological mecha-
nisms of pomegranate and the individual constituents
responsible for them. Extracts of all parts of the fruit
appear to have therapeutic properties,
and some stud-
ies report the bark, roots, and leaves of the tree have
medicinal benefit as well.
Current research seems to
indicate the most therapeutically beneficial pomegran-
ate constituents are ellagic acid ellagitannins (including
punicalagins), punicic acid, flavonoids, anthocyanidins,
anthocyanins, and estrogenic flavonols and flavones.
Table 1 lists the principal constituents of the Punica
granatum tree and fruit. Figure 1 depicts the structure
of ellagic acid.
Table 1. Pomegranate Fruit Parts and Constituents
Pomegranate juice
Pomegranate seed oil
Pomegranate pericarp
(peel, rind)
Pomegranate leaves
Pomegranate flower
Pomegranate roots and bark
glucose, ascorbic acid;
ellagic acid, gallic acid,
caffeic acid;
catechin, EGCG;
quercetin, rutin;
minerals, particularly iron;
amino acids
95-percent punicic acid;
other constituents, including ellagic
other fatty acids;
phenolic punicalagins; gallic acid and other fatty acids;
catechin, EGCG;
quercetin, rutin, and other flavonols;
tannins (punicalin and punicafolin); and flavone glycosides,
including luteolin and apigenin
gallic acid, ursolic acid;
triterpenoids, including maslinic and
asiatic acid;
other unidentified constituents
ellagitannins, including punicalin and punicalagin;
piperidine alkaloids
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Figure 1. Structure of Ellagic Acid
Constituent Standardization versus
e goal of many pomegranate studies has
been to identify the therapeutic constituents. Common-
ly found in many plants, ellagic acid exhibits powerful
and antioxidant
properties, propel-
ling it to the forefront of pomegranate research. Many
commercially available pomegranate extracts are being
standardized to contain 40-percent (or more) ellagic
acid; however, Lansky, a prominent researcher on the
medicinal properties of pomegranate, cautions against
focusing on ellagic acid standardization to the exclusion
of other therapeutically important pomegranate constit-
Research on ellagic acid with other flavonoids
such as quercetin supports his contention.
sky’s research confirms the synergistic action of several
pomegranate constituents is superior to ellagic acid in
suppressing prostate cancer.
To quote Lansky, “e
recent profusion onto the nutraceuticals marketplace of
products standardized to 40 percent (or even higher)
ellagic acid represents a cynical, lucre-driven attempt to
replace the power of the pomegranate with the power
of ellagic acid. e pomegranate needs no such tricks
or enhancements. It is rather an extraordinary, albeit
mysterious (and messy), fruit with a complete medicinal
power contained within its juice, peel, and seeds.
Although little is known about the metabolism
and bioavailability of ellagitannins from food sources,
three small human trials and one case study have inves-
tigated the bioavailability, absorption, metabolism, and
in vivo antioxidant effects of pomegranate. In the case
study, consumption of 180 mL pomegranate juice (PJ)
by a single subject yielded 31.9 ng/mL plasma ellagic
acid at one hour, with rapid plasma clearance by four
hours post-ingestion. is was the first direct evidence
that ellagic acid consumed from food was absorbed in
A study of 18 healthy volunteers by the same
researchers confirmed the rapid absorption and plasma
clearance of ellagitannins and also confirmed urolithin
metabolites excreted in the urine can persist for 48 hours
after pomegranate juice ingestion, thereby suggesting an
explanation of the benefits of long-term pomegranate
In a 13-day clinical trial involving six healthy
subjects (4 men and 2 women), one liter of PJ contain-
ing 4.37 g/L punicalagins and 0.49 g/L anthocyanins
was consumed by all six subjects for five days. ree
pomegranate juice metabolites were detected in the
plasma – urolithin A, urolithin B, and a third unidenti-
fied minor metabolite; urinalysis at 24 hours revealed
six metabolites – the three found in the plasma as well
as an aglycone metabolite corresponding to each of three
plasma metabolites. Maximum excretion rates occurred
3-4 days after juice ingestion. Significant variability of
urinary metabolite concentrations was observed among
subjects and may be attributable to differences in co-
lonic microflora, where the ellagitannins are believed to
be metabolized.
e persistence of urolithin A and B
in the urine may be responsible for pomegranates long-
term antioxidant effects, rather than the polyphenols
found in the juice.
In another study, 11 healthy men and women
were placed on a polyphenol- and antioxidant-free diet
for three days prior to consuming pomegranate extract
(plant parts used were not specified). Subjects were
given 800 mg capsuled pomegranate extract daily con-
taining 330.4 mg punicalagins and 21.6 mg ellagic acid
(EA). C
and T
for plasma EA was 33.8±12.7 ng/
mL at one hour post-ingestion, similar to values ob-
served in the case study when similar amounts of pu-
nicalagins and EA were administered. is study also
demonstrated a significant increase (31.8%) in plasma
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Alternative Medicine Review Volume 13, Number 2 2008
Review Article
Page 131
antioxidant capacity 30 minutes after extract adminis-
tration; one and two hours post ingestion, values were
increased 1.62- and 1.43-fold, respectively.
Mechanisms of Action
Although pomegranates wide-ranging thera-
peutic benefits may be attributable to several mecha-
nisms, most research has focused on its antioxidant,
anticarcinogenic, and anti-inflammatory properties.
Antioxidant Mechanisms
An in vitro assay using four separate testing
methods demonstrated pomegranate juice and seed
extracts have 2-3 times the antioxidant capacity of ei-
ther red wine or green tea.
Pomegranate extracts have
been shown to scavenge free radicals and decrease mac-
rophage oxidative stress and lipid peroxidation in ani-
and increase plasma antioxidant capacity in el-
derly humans.
Studies in rats and mice confirm the antioxi-
dant properties of a pomegranate by-product (PBP)
extract made from whole fruit minus the juice, show-
ing a 19-percent reduction in oxidative stress in mouse
peritoneal macrophages (MPM), a 42-percent decrease
in cellular lipid peroxide content, and a 53-percent in-
crease in reduced glutathione levels.
In vitro assay of a
fermented pomegranate juice (FPJ) extract and a cold-
pressed seed oil (CPSO) extract found the antioxidant
capacity of both are superior to red wine and similar to
green tea extract.
A separate study in rats with CCl
induced liver damage demonstrated pretreatment with
a pomegranate peel extract (PPE) enhanced or main-
tained the free-radical scavenging activity of the hepatic
enzymes catalase, super oxide dismutase, and peroxi-
dase, and resulted in 54-percent reduction of lipid per-
oxidation values compared to controls.
Research in humans has shown a juice made
from pomegranate pulp (PPJ) has superior antioxidant
capacity to apple juice. Using the FRAP assay (ferric
reducing/antioxidant power), Guo et al found 250 mL
PPJ daily for four weeks given to healthy elderly sub-
jects increased plasma antioxidant capacity from 1.33
mmol to 1.46 mmol, while subjects consuming apple
juice experienced no significant increase in antioxidant
capacity. In addition, subjects consuming the PPJ exhib-
ited significantly decreased plasma carbonyl content (a
biomarker for oxidant/antioxidant barrier impairment
in various inflammatory diseases) compared to subjects
taking apple juice. Plasma vitamin E, ascorbic acid, and
reduced glutathione values did not differ significantly
between groups, leading researchers to conclude pome-
granate phenolics may be responsible for the observed
Anticarcinogenic Mechanisms
In vitro assays utilizing three prostate cancer
cell lines (DU-145, LNCaP, and PC-3) demonstrated
various pomegranate extracts (juice, seed oil, peel) po-
tently inhibit prostate cancer cell invasiveness and pro-
liferation, cause cell cycle disruption, induce apoptosis,
and inhibit tumor growth. ese studies also demon-
strated combinations of pomegranate extracts from
different parts of the fruit were more effective than any
single extract.
Several animal studies have elucidated pome-
granates potential anticancer mechanisms. Two studies
in mice implanted with the prostate cancer PC-3 cell
line demonstrated pomegranate fruit extract (PFE; ed-
ible parts of the fruit, excluding the peel) inhibits cell
growth and induces apoptosis via modulation of pro-
teins regulating apoptosis.
In an open-label, phase II clinical trial in 46
men with recurrent prostate cancer, 16 patients (35%)
showed a significant decrease in serum prostate specific
antigen (PSA) levels (average=27%) during treatment
with eight ounces of pomegranate juice. Corresponding
in vitro assays using patient plasma and serum dem-
onstrated significant decreases in prostate cancer cell
line proliferation and increased apoptosis. Nitric oxide
preservation via ingestion of pomegranate polyphenols
significantly correlated with lower PSA values. ese
results indicate pomegranate may affect prostate cancer
because of antiproliferative, apoptotic, antioxidant, and
possibly anti-inflammatory effects.
Recent research also indicates pomegranate
constituents inhibit angiogenesis via downregulation of
vascular endothelial growth factor in MCF-7 breast can-
cer and human umbilical vein endothelial cell lines.
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Anti-inflammatory Mechanisms
Cold pressed pomegranate seed oil has been
shown to inhibit both cyclooxygenase and lipoxygenase
enzymes in vitro. Cyclooxygenase, a key enzyme in the con-
version of arachidonic acid to prostaglandins (important
inflammatory mediators), was inhibited by 37 percent by
a CPSO extract. Lipoxygenase, which catalyzes the con-
version of arachidonic acid to leukotrienes, also key me-
diators of inflammation, was inhibited by 75 percent by a
CPSO extract. By comparison, an FPJ extract resulted in
a 23.8-percent inhibition of lipoxygenase in vitro.
Another in vitro study that may have far-reaching
implications for those suffering from osteoarthritis (OA)
demonstrated PFE has a significant and broad inhibitory
effect on matrix metalloproteinases (MMPs), a subgroup
of collagenase enzymes expressed in high levels in arthritic
joints and involved in the turnover, degradation, and ca-
tabolism of extracellular joint matrix. In pretreated hu-
man femoral OA chondrocytes, PFE inhibited IL-1beta-
induced destruction of proteoglycan, expression of MMPs
at the cellular level, and phosphorylation and activation of
mitogen-activated protein kinases (signal transduction
molecules involved in MMP expression). e suppres-
sion of MMP expression in OA chondrocyte cultures by
PFE suggests pomegranate constituents prevent collagen
degradation and may inhibit joint destruction in OA pa-
Other Mechanisms
A pilot study in type 2 diabetic patients with hy-
perlipidemia found concentrated PJ decreased cholesterol
absorption, increased fecal excretion of cholesterol, had a
beneficial effect on enzymes involved in cholesterol me-
tabolism, significantly reduced total and LDL cholesterol,
and improved total/HDL and LDL/HDL cholesterol
PJ consumption by hypertensive patients inhib-
its serum angiotensin converting enzyme (ACE; a cata-
lyst for the conversion of angiotensin I to angiotensin II, a
potent vasoconstrictor) activity, thereby reducing systolic
blood pressure
and potentially protecting against car-
diovascular disease.
Animal studies have revealed three possible hy-
poglycemic mechanisms for Punica granatum extracts.
Pomegranate flower extract (PFLE) improved insulin
sensitivity and lowered glucose levels in rats as early as 30
minutes post-glucose loading. PFLE also inhibited alpha-
glucosidase in vitro, thereby decreasing the conversion of
sucrose to glucose.
PPE demonstrates significant hypo-
glycemic activity in diabetic rats, via enhanced insulin lev-
els and regeneration of pancreatic beta cells.
Numerous in vitro studies
and two human
demonstrate the antimicrobial activity of pome-
granate extracts. e growth of Staphylococcus aureus,
Streptococcus pyogenes, Diplococcus pneumoniae, Escheri-
chia coli O157:H7, and Candida albicans was inhibited
via direct bacteriocidal or fungicidal activity.
Clinical Applications
Prostate Cancer
Among males in the United States and other
Western countries, prostate cancer is the second-lead-
ing cause of cancer-related death. In vitro studies show
several PFEs inhibit prostate cancer cell growth, induce
apoptosis of several prostate cancer cell lines (including
highly aggressive PC-3 prostate carcinoma cells), sup-
press invasive potential of PC-3 cells, and decrease pro-
liferation of DU-145 prostate cancer cells.
et al found combining equal amounts of FPJ, PPE, and
CPSO extracts resulted in a 99-percent suppression of
DU-145 prostate cancer cell invasion across a Matrigel
matrix. CPSO extract or FPJ extract alone resulted in
60-percent suppression of invasion, and combining any
two extracts induced 90-percent suppression. Studies
in mice have also demonstrated PFE inhibits prostate
tumor growth and decreases PSA levels.
ese promising results led some of the same
researchers to conduct a two-stage phase II clinical trial
in men with recurrent prostate cancer and rising PSA
levels. All eligible patients had previous surgery or ra-
diation therapy for prostate cancer, Gleason scores (a
grading system for predicting the behavior of prostate
cancer) ≤7, rising PSA value of 0.2-5.0 ng/mL, no
prior hormonal therapy, and no evidence of metastases.
Baseline PSA doubling times were established for 22
participants who were then started on eight ounces PJ
(570 mg total polyphenol gallic acid equivalents) daily
until meeting disease progression endpoints. Endpoints
measured were: effect on PSA levels, serum lipid per-
oxidation and nitric oxide levels, in vitro induction of
proliferation and apoptosis of LNCaP cells in patient
serum containing pomegranate constituents, and over-
all safety of extract administration.
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Based on preliminary results achieved in phase
I, 24 additional patients were enrolled and 46 patients
were evaluated over 13 months in both stages of the
trial. Of these, 35 percent (n=16) demonstrated de-
creased PSA levels, the primary trial endpoint average
decrease=27%; median decrease=18%; range 5-85%.
Four of 46 patients (8.7%) met objective response cri-
teria and exhibited >50-percent reduction in PSA val-
ues, meeting criteria for a phase III trial. In addition, an
average 40-percent reduction in serum oxidative state
was observed in patients accompanied by a significant
reduction in serum lipid peroxidation compared to
baseline. Nitric oxide serum metabolites measured at
nine months after study initiation revealed an average
23-percent increase, which significantly correlated with
baseline PSA levels.
An in vitro arm of the trial using patient serum
investigated whether PJ consumption had any effect on
growth rates or apoptosis of LNCaP prostate cancer
cells in culture. Serum collected at nine months after
study initiation and incubated with LNCaP decreased
cell growth by an average of 12 percent in 84 percent
of patients compared to baseline. An average 17.5-per-
cent increase in apoptosis in 75 percent of patients was
also noted. is study indicates PJ or PJ constituents
may have promise as a therapy for prostate cancer, par-
ticularly recurrent type with rising PSA levels; phase III
studies are currently underway.
Other Cancer Types
Numerous in vitro studies have investigated the
therapeutic effect of pomegranate extracts against sev-
eral other cancer cell lines. In HT-29 colon cancer cells,
cyclooxygenase-2 (COX-2) expression is increased via
activation of nuclear factor kappa-B (NFκB) by tumor
necrosis factor-alpha (TNF-α), an inflammatory cell
signaling process that may be a cause of cancer initia-
tion and progression. Treatment of HT-29 colon can-
cer cells with PJ, total pomegranate tannins, or concen-
trated pomegranate punicalagin induced a significant
decrease in COX-2 expression. PJ treatment resulted
in the highest level of COX-2 suppression (79%) com-
pared to treatment with single constituents. e effects
were attributed to synergistic activity of the bioactive
constituents thought to be necessary for pomegranates
anti-inflammatory and anticarcinogenic activity.
Another in vitro study investigated the effects
of punicalagin, ellagic acid, total pomegranate tannins,
and PJ on several cell lines. Although all preparations
decreased viable cell numbers in KB and CAL-27 oral
cancer cell lines, as well as in HT-29 and HCT-116
colon cancer cell lines, a higher degree of suppression
was obtained with pure PJ, an affect attributed to the
synergy of its bioactive constituents.
Research utilizing breast cancer cell lines
MCF-7 and MB-MDA-231 demonstrates pomegran-
ate constituents effectively inhibit angiogenesis,
proliferation, and invasiveness,
and induce
To examine the effect of FPJ and CPSO
extracts, and an HPLC-isolated peak B (from the fruit
extract), Mehta and Lansky used the mouse mammary
organ culture, an animal model of breast cancer having
≥75-percent accuracy of predicting in vivo carcinogen-
esis. ey found cancerous glands treated with each
pomegranate compound exhibited decreased lesion
incidence 37 percent for FPJ, and 75-90 percent for
both peak B and CPSO. Seed oil is comprised mainly of
punicic acid, a trienoic acid with anticarcinogenic prop-
erties and effective at very low doses (1 mg/mL in organ
culture). Peak B is believed to be a phenolic compound
with potent chemopreventative properties.
Research in mice has shown PFE inhibits tum-
origenesis in lung cancer and skin cancer models. In the
lung cancer study, mice given daily oral dosages of PFE
comparable to what humans could reasonably consume
(exact dosages were not available) exhibited significantly
less lung tumor growth than mice not receiving PFE.
In mice treated with skin-cancer-inducing 12-O-tet-
radecanoylphorbol-13-acetate (TPA), animals treated
topically with PFE had significantly reduced incidence
of skin tumors. In the PFE-treated group, only 30 per-
cent of mice exhibited tumors compared to 100 percent
of mice treated with TPA and no PFE. is result was
attributed to suppression of inflammation (COX-2,
MAPKs, NFκB) and the tumor proliferation marker
ornithine decarboxylase.
Lansky and Kuwaii investigated the effect of
flavonoid-rich PJ and FPJ and pomegranate pericarp
extracts on HL-60 human leukemia cell differentia-
tion (the ability of cancer cells to revert to normal cells)
and proliferation. Because of the structural similarity
between plant flavonoids and retinoids (the latter be-
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Page 134
established pro-differentiating agents), it was
h y p o t h
esized that flavonoid-rich pomegranate extracts
might have a similar effect on differentiation. In vitro
assays confirmed both the FPJ and pericarp extracts
strongly promoted cellular differentiation and inhibited
proliferation in HL-60 cell cultures; the effect of PJ on
cellular differentiation was less significant. is study
suggests another mechanism by which pomegranate
constituents impart an anticarcinogenic effect.
In vitro, animal, and human trials have exam-
ined the effects of various pomegranate constituents on
prevention and attenuation of atherosclerosis. One of
the preeminent researchers in endothelial function and
nitric oxide (NO) biochemistry, Louis J. Ignarro, PhD,
investigated the effects of pomegranate juice and other
fruit juices on endothelial function, comparing propen-
sities to protect NO from destruction by reactive oxy-
gen species in vitro. Results of the antioxidant portion
of the study demonstrate pomegranate juice possesses
significantly greater antioxidant capacity at much lower
concentrations (>1000-fold dilutions) than either grape
or blueberry juice, which was attributed to the high an-
thocyanin flavonoid content and higher total flavonoid
content in PJ than the other juices.
Because impaired endothelial function is an
early indicator of atherosclerosis, this study examined
the effect of PJ on proliferation of rat aortic smooth
muscle cells in culture. PJ proved superior to other
juices, significantly enhancing NO’s effect on cardiac
endothelium even at 2,000-fold dilutions. PJ did not
influence endothelial nitric oxide synthase (eNOS)
expression, leading Ignarro et al to conclude the anti-
oxidant properties of PJ protect NO from free radical
destruction and augment the antiproliferative action of
NO on rat aortic smooth muscle cells.
In early-stage atherosclerosis, elevated plasma
cholesterol, increased oxidative stress, and increased
cholesterol esterification rates are factors contributing
to foam cell formation and development of athero-
sclerotic lesions.
Research in atherosclerotic apoli-
poprotein-E deficient (E°) mice by Aviram et al at the
Lipid Research Laboratory in Haifa, Israel, has focused
on the ability of pomegranate extracts to inhibit athero-
Two months of PJ to E° mice with advanced
atherosclerosis reduced MPM lipid peroxide content by
42 percent compared with placebo-treated mice; MPM
lipid peroxide content in PJ-treated mice was 20-per-
cent lower than in four-month-old control mice. In ad-
dition, MPM harvested from PJ-treated mice exhibited
80-percent lower rates of cholesterol esterification than
placebo-treated mice. In PJ-treated mice atherosclerotic
lesion size in the aorta was 17-percent smaller than in
the age-matched placebo group. PJ and an isolated tan-
nin fraction from PJ were also given to young mice
prior to development of significant atherosclerosis.
Researchers found 25- and 17-percent reductions in
plasma lipid peroxide concentrations with the isolated
tannin fraction and PJ, respectively.
Aviram et al also investigated the anti-ath-
erosclerotic effects of a PBP extract after the juice was
removed. Four-month-old E° mice with significant ath-
erosclerosis were given PBP extract (containing 51.5
µg gallic acid equiv/kg/day) with an eight-fold higher
polyphenol concentration than PJ for three months.
is resulted in a significant reduction in MPM oxida-
tive status as evidenced by a 27-percent decrease in to-
tal macrophage peroxide levels, a 42-percent decrease in
cellular lipid peroxide levels, and a 19-percent decrease
in peritoneal macrophage uptake of oxidized LDL.
To further identify the most potent anti-athero-
genic pomegranate components, Aviram et al analyzed
several more pomegranate extracts from all parts of the
plant. Atherosclerotic mice were given six different
pomegranate preparations with varying amounts of to-
tal polyphenols and gallic acid content for three months.
Antioxidant activity, atherosclerotic lesion size, MPM
oxidative status, blood sugar, and lipid profiles were ex-
amined. Confirming earlier results, this study demon-
strated PFLE more significantly affects atherosclerotic
lesion size (Figure 2), lipid profiles, and blood sugar lev-
els than other extracts tested; two PPEs demonstrated
the most potent antioxidant effects. Mechanisms associ-
ated with the anti-atherogenic effects of pomegranate in
this study include increased MPM uptake of oxidized
LDL, decreased lipid peroxidation, and decreased cho-
lesterol levels.
e effect of PJ consumption on lipid per-
oxidation in plasma and HDL- and LDL-lipoproteins
was examined in a double-armed human trial. In the
first study, 13 healthy, nonsmoking men (ages 20-35)
were given 50 mL PJ daily (containing 1.5 mmol total
polyphenols) for two weeks. In the second study (dura-
tion ≤10 weeks), three healthy men (same age range)
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Review Article
Page 135
were given increasing doses of PJ ranging from 20-80
mL daily (0.54-2.16 mmol total polyphenols). Fasting
blood samples were drawn from participants pre-study
and after one and two weeks of PJ supplementation.
No significant effect was observed in either study on
plasma lipid profile or lipoprotein patterns. e results
did show, however, for the first time in humans, that PJ
has an inhibitory effect on lipid peroxidation in plasma
and in lipoproteins, with the middle dose (50 mL daily)
being the most effective, yielding a 32-percent decrease
in plasma lipid peroxidation. PJ (in a dose-dependent
manner) also demonstrated up to 90-percent inhibi-
tion of collagen-induced platelet aggregation in human
platelets ex vivo.
Pomegranate flowers have been used in both
the Unani and Ayurvedic systems of medicine as a
remedy for diabetes. Based on historical use, a study in
diabetic rats explored the effects of PFLE on cardiac
lipid metabolism in 13-
to 15-week old Zucker
diabetic rats. Animals
were given 500 mg/kg
PFLE or placebo for six
weeks, and total choles-
terol, triglyceride, and
nonesterified free fatty
acids (NEFA) were de-
termined prior to treat-
ment (nonfasting), at
week 4 (nonfasting), and
week 5 (fasting) in both
rat plasma and cardiac
tissue. PFLE was shown
to activate peroxisome
receptor (PPAR-α), a
cardiac transcription fac-
tor involved in myocar-
dial energy production
via fatty acid uptake and
oxidation. PPAR-α acti-
vation decreased cardiac
uptake and circulation
of lipids. Decreases were
observed in cardiac tissue
triglyceride content at the
end of the study and in plasma total cholesterol and
NEFA after four weeks of treatment.
A pilot study involving 22 type 2 diabetic pa-
tients (8 men and 14 women) investigated the choles-
terol-lowering effects of 40 g concentrated PJ for eight
weeks. Statistically significant decreases were observed
in total cholesterol (from 202.4±27.7 mg/dL at baseline
to 191.4±21 mg/dL at study conclusion), LDL choles-
terol (124.4±31.9 mg/dL at baseline to 112.9±25.9
mg/dL at study conclusion), total/HDL cholesterol ra-
tio (5.5±1.3 at baseline to 5.1±1.1 at study conclusion),
and LDL/HDL ratio (3.4±1.2 at baseline to 3.0±0.9 at
study conclusion). e authors attributed these effects
to decreased absorption and increased fecal excretion of
cholesterol, as well as possible affects on HMG-CoA
reductase and sterol O-acyltransferase, two enzymes
key to cholesterol metabolism.
Figure 2. Atherosclerotic Lesion Size with Various Pomegranate Extracts
Pomegranate Fruit
Liquid Extract
Pomegranate Polyphenol
Powder Extract
Pomegranate Juice
Flower Extract
Pomegranate Ground
Arils & Seeds
Atherosclerotic Lesion Size (µm
38% decrease
39% decrease
44% decrease
6% decrease
Aviram M, Volkova N, Coleman R, et al. Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies
in vivo in atherosclerotic apolipoprotein E-deficient (E°) mice and in vitro cultured macrophages and lipoproteins. J Agric
Food Chem 2008;56:1148-1157.
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Alternative Medicine Review Volume 13, Number 2 2008
Page 136
A small clinical trial demonstrated PJ inhib-
its serum ACE and reduces systolic blood pressure in
hypertensive patients. Ten hypertensive subjects (ages
62-77; seven men and three women) were given 50 mL/
day PJ containing 1.5 mmol total polyphenols for two
weeks. Two of seven patients were also diabetic and two
were hyperlipidemic. Seven of 10 subjects (70%) expe-
rienced a 36-percent average decrease in serum ACE ac-
tivity and a small, but significant, five-percent decrease
in systolic blood pressure.
Carotid Artery Stenosis
In a small, long-term study, 19 subjects (ages
65-75) with severe carotid artery stenosis (70-90%
stenosis of internal carotid arteries) were randomized
to receive either 50 mL PJ daily containing 1.5 mmoles
total polyphenols (n=10) or no treatment (n=9) for
one year; five subjects continued PJ for an additional
two years. Study participants were treated with similar
hypocholesterolemic and antihypertensive medications
and no dietary or lifestyle changes occurred in either
group. Blood samples were collected and echo Doppler
analysis was performed at baseline and at 3, 6, 9, 12,
22, 28, and 36 months. Control subjects demonstrated
a mean nine-percent increase in intima-media thick-
ness (IMT) of left and right carotid arteries during the
first year. Conversely, those consuming PJ had reduced
IMT at 3, 6, 9, and 12 months ranging from 13 percent
at three months to 35 percent at one year compared to
baseline values.
Most serum biochemistry parameters re-
mained unchanged by PJ consumption over the first
year, with the exception of triglyceride concentrations,
which increased 16 percent but remained in the normal
range. Serum lipid peroxidation in subjects consum-
ing PJ was significantly reduced by 59 percent after
one year, and levels of LDL-associated lipid peroxides
Table 2. Antioxidant Activity of Pomegranate Juice Extract in Patients
with Carotid Artery Stenosis
Total Antioxidant Status
Serum Antibodies against
LDL Oxidation (EU/mL)
AAPH-induced Serum Lipid
Peroxidation (nmol/mL)
Serum Paraoxonase
1 (PON1) Arylesterase
Activity (Units/mL)
Lipid Peroxide Content of
Carotid Lesions (nmol/mg
of lesion protein)
0.95 ± 0.12
2670 ± 61
1670 ± 66
56 ± 5
1563 ± 69
1670 ± 52
2.20 ± 0.23
691 ± 43
97 ± 10
107 ± 10
EU = Enzyme units
AAPH = 2.2’-azobis, 2-amidinopropane hydrochloride
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Page 137
were also decreased by as much as 90 percent after six
months of supplementation. Body mass index did not
change in treated subjects but systolic blood pressure
was reduced an average of 16 percent during the three-
year study.
In addition to previous reports of reduced
systolic blood pressure
and inhibition of lipid peroxi-
this study demonstrated that PJ consumption
(via antioxidative mechanisms) significantly reduces
various aspects of IMT in patients with severe carotid
artery stenosis (Table 2).
Myocardial Perfusion
In a double-blind, randomized, placebo-con-
trolled trial, 39 patients were given either 240 mL PJ
(polyphenol content not specified) (n=23) or a sports
beverage of similar color, flavor, and caloric content
daily for three months (n=16). Although both control
and treatment patients demonstrated similar levels of
stress-induced ischemia at baseline, at three months
stress-induced ischemia increased in the placebo group
(from 5.9±4.3 to 7.1±5.5) but decreased in the treat-
ment group (from 4.5±3.1 to 3.7±3.7). In addition, an-
gina episodes increased 38 percent in the placebo group
but decreased 50 percent in the treatment group (a net
change of 88 percent). ese results demonstrate a re-
duction in myocardial ischemia and improved myocar-
dial perfusion (as measured by stress-induced ischemia)
in patients consuming pomegranate juice.
In an animal model of diabetes, Huang et al dem-
onstrated the favorable effect of PFLE on lipid profiles
and cardiac fibrosis
of Zucker fatty diabetic rats. Rosen-
blat et al investigated the effect of 50 mL/day PJ for three
months on oxidative stress, blood sugar, and lipid profiles
in 10 type 2 diabetic patients (history of diabetes for 4-10
years) and 10 healthy controls (ages 35-71).
In diabetic
patients, triglyceride levels were 2.8 times greater, HDL
cholesterol was 28-percent lower, and hemoglobin A1C
(HbA1C) values were 59-percent higher than in control
patients. Insulin was only slightly lower in patients than
controls, and C-peptide (a proinsulin metabolite marker
for endogenously secreted insulin) was slightly higher in
diabetic patients than in healthy controls at baseline (indi-
cating slight hyperinsulinemia). Consuming PJ for three
months did not significantly affect triglyceride, HDL
cholesterol, HbA1C, glucose, or insulin values, but did
lower serum C-peptide values by 23 percent compared to
baseline in diabetic patients – a sign of improved insulin
PJ consumption also significantly reduced oxi-
dative stress in the diabetic patients as evidenced by a
56-percent reduction in lipid peroxides and a 28-percent
reduction in TBARS compared to baseline serum levels.
In addition, a 39-percent decrease in uptake of oxidized
LDL by human monocyte-derived macrophages (an early
development in foam cell formation and atherogenesis)
was observed in diabetic patients after PJ consumption.
Researchers concluded that despite the sugars naturally
present in pomegranate juice, consumption did not ad-
versely affect diabetic parameters but had a significant ef-
fect on atherogenesis via reduced oxidative stress.
Dental Conditions
Topical applications of pomegranate prepara-
tions have been found to be particularly effective for
controlling oral inflammation, as well as bacteria and
fungal counts in periodontal disease and Candida-asso-
ciated denture stomatitis.
Dental Plaque
A hydroalcoholic extract of Punica granatum
fruit (HAEP) was investigated for antibacterial effect
on dental plaque microorganisms. Sixty healthy patients
(33 females/27 males; ages 9-25) with fixed orthodon-
tic appliances were randomized to three groups of 20:
(1) control group who rinsed with 15 mL distilled wa-
ter; (2) a group who rinsed with 15 mL chlorhexidine,
a standard antiplaque mouth rinse; and (3) a group who
rinsed with a 15-mL HAEP solution. Rinsing duration
was one minute and dental plaque material was collected
from each patient prior to and after rinsing. Samples were
diluted and plated on Meuller-Hinton agar and incuba-
ted at 37° C for 48 hours. HAEP decreased the number
of colony forming units (CFU) of dental plaque bacteria
84 percent, comparable to chlorhexidine (79-percent in-
hibition) but significantly better than the control rinse
(11-percent inhibition). Both HAEP and chlorhexidine
were effective against Staphylococcus, Streptococcus,
Klebsiella, and Proteus species, as well as E. coli. e
ellagitannin, punicalagin, is thought to be the fraction
responsible for pomegranates antibacterial activity.
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Periodontal Disease
A preliminary and follow-up study by a group
of ai researchers investigated the effect of biodegrad-
able chips impregnated with Centella asiatica and P. gra-
natum pericarp on periodontal disease in 20 patients
with gum pocket depths of 5-8 mm. A baseline exam
was performed and followed by root planing and scal-
ing of target teeth. Subgingival placement of the medi-
cated chips (treatment group) and non-medicated chips
(placebo/control group) followed, and pocket depth,
attachment level, bleeding, and gingival and plaque in-
dexes were measured at baseline and after three and six
months. All treatment sites demonstrated a trend to-
ward decreasing plaque and significant improvements
were noted in pocket depth and attachment level at
three months compared to placebo.
In the follow-up study, 15 patients who had
completed standard periodontal therapy but still had
pocket depths of 5-8 mm were implanted with the same
medicated chips. e same parameters were measured
again at baseline and after three and six months, but
researchers also measured inflammatory markers inter-
leukin-1ß (IL-1ß) and IL-6. Significant improvement
was noted in all re-measured parameters and confirmed
by significant decreases in IL-1ß and IL-6 at three and
six months compared to baseline.
Denture Stomatitis
e primary etiologic factors for denture stom-
atitis are poor oral hygiene, inflammation from ill-fitting
dentures, and Candida infection,
which manifest as
swelling, pain, burning in the mouth, and aphthous ul-
In a randomized, double-blind study of 60 sub-
jects (ages 19-62) with candidiasis confirmed via myco-
logic examination, the effect of a gel-based P. granatum
bark extract (GPBE) was evaluated for its effect on heal-
ing of oral lesions and direct fungicidal effect. Patients
were randomized into two groups of 30: one received
miconazole oral gel (a standard therapy) and the other
used GPBE, both three times daily for 15 days. Gels
were applied to oral surfaces, dentures were removed
and cleaned nightly, then brushed with the correspond-
ing oral gels. All subjects reported an improvement in
symptoms and general oral health. Clinical symptoms of
those using miconazole were slightly better (27/30 sat-
isfactory improvement) compared to GPBE (21/30 sat-
isfactory improvement). Clearing of Candida infection
was approximately the same in both groups (25/30 in the
miconazole group and 23/30 in the GPBE group).
Interestingly, despite randomized subject place-
ment, there were three times more subjects with good
oral hygiene scores in the miconazole group compared
to the GPBE group, possibly accounting for the superior
results observed by miconazole therapy. Also, because
the initial step in the development of Candida denture
stomatitis is adherence of organisms to dentures and the
miconazole gel was stickier than GPBE, contact dura-
tion of miconazole was longer. A stickier GPBE might
result in improved clinical response.
Bacterial Infections
e only human trials examining the antibac-
terial properties of pomegranate extracts have focused
on oral bacteria.
However, several in vitro assays
demonstrate its bacteriocidal activity against several
highly pathogenic and sometimes antibiotic-resistant
organisms. Brazilian researchers evaluated the synergis-
tic effect of a P. granatum methanolic extract with five
antibiotics on 30 clinical isolates of methicillin-resistant
Staphylococcus aureus (MRSA) and methicillin-sensitive
S. aureus.
Antibiotics tested were chloramphenicol, gen-
tamicin, ampicillin, tetracycline, and oxacillin. Although
synergistic activity between the pomegranate extract
and all five antibiotics was noted in the S. aureus isolates,
synergy with ampicillin was the most pronounced. A
combination of the two increased the lag time to bacter-
ial growth by three hours (over that of ampicillin alone)
and was also bacteriocidal as evidenced by a 72.5-per-
cent reduction in methicillin-sensitive organisms and a
99.9-percent reduction in MRSA. Based on earlier re-
and the results of this study, the ellagitannin,
punicalagin, is thought to be the primary constituent
responsible for the observed antibacterial effects.
Another organism that can cause significant dis-
ease in humans is enterohemorrhagic Escherichia coli (E.
coli O157:H7), which can present with diarrhea, hem-
orrhagic colitis, thrombocytopenic purpura, and hemo-
lytic uremic syndrome. P. granatum and seven other ai
medicinal plant extracts were tested for in vitro activity
against E. coli O157:H7. An ethanolic PPE, one of the
two most effective extracts against E. coli O157:H7, was
shown to be both bacteriostatic and bacteriocidal, indi-
cating PPE may be an effective adjunct treatment for E.
coli O157:H7 infection.
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Page 139
Ultraviolet Radiation
In vitro studies using normal human epidermal
keratinocytes and PFE demonstrate PFE incubation
with cell cultures ameliorates ultraviolet A and B radia-
tion-induced cell damage in a dose- and time-dependent
manner, providing evidence at a cellular level that PFE
may be an effective photo-chemopreventive agent.
A double-blind, placebo-controlled trial eval-
uated the protective and ameliorative properties of
pomegranate extract and its EA constituent on UV-
induced skin pigmentation. An ethanolic PPE was pre-
pared containing 89.5 percent EA, confirmed by HPLC
analysis. irty-nine healthy women (ages 20-49) were
randomly assigned to one of three groups: (1) high-
dose (200 mg/day) EA tablets; (2) low-dose (100 mg/
day) EA tablets; and (3) placebo (0 mg EA) tablets for
four weeks. Prior to the first dose, subjects received a
1.5 minimum erythema dose (MED) of UV radiation
on the inside upper right arm. Melanin, luminance, and
erythema values were measured at baseline and at the
end of each of the next four weeks. A questionnaire
was completed by subjects to evaluate PPE’s effective-
ness on improvement of UV-induced slight sunburn.
Rate of change for luminance, melanin, and erythema
values was not significantly different for subjects receiv-
ing either EA dose compared to placebo or compared
to baseline values. However, analysis of the question-
naire results demonstrated a trend toward amelioration
of UV-induced damage in both EA groups compared
to placebo.
Erectile Dysfunction
A study using a rabbit model of arteriogenic
erectile dysfunction (ED) measured the effect of PJ
concentrate on intracavernous blood flow and penile
erection. Azadzoi et al found eight weeks administra-
tion of 3.87 mL PJ concentrate (112 µmol polyphenols)
daily significantly increased intracavernous blood flow
and smooth muscle relaxation, probably via its antioxi-
dant effect on enhanced NO preservation and bioavail-
A randomized, double-blind, placebo-con-
trolled, 10-week crossover trial in 53 men (mean age
46) investigated PJs therapeutic effect on mild-to-
moderate ED. Subjects with other medical conditions
that might contribute to ED were excluded, and sub-
jects were asked to refrain from taking ED medication
for the duration of the study. e trial consisted of two
four-week treatment periods separated by a two-week
washout. During the first four weeks, subjects were
given PJ (1.5 mmol polyphenols daily) or placebo bev-
erage, followed by washout and crossover to the other
group. Although assessment via the International Index
of Erectile Function and Global Assessment Question-
naires demonstrated a trend toward improvements in
ED, statistical significance was not achieved. is may
be attributable to small sample size, short study dura-
tion, subject compliance with beverage consumption, or
may indicate the PJ dosage did not have an appreciable
effect on ED.
Male Infertility
Research in rats demonstrates PJ consumption
improves epididymal sperm concentration, spermato-
genic cell density, diameter of seminiferous tubules, and
sperm motility, and decreases the number of abnormal
sperm compared to control animals. An improvement
in antioxidant enzyme activity in both rat plasma and
sperm was also noted.
Neonatal Hypoxic-Ischemic Brain Injury
Neonatal hypoxic-ischemic (HI) brain injury
in severely preterm, very low birth-weight infants is a
major cause of infant illness and death
and has been
associated with an increase in reactive oxygen species.
Two studies in which pregnant mice were given PJ in
drinking water revealed the neonatal offspring, when
subjected to experimentally-induced HI brain injury,
had significantly less brain tissue loss (64% decrease)
and significantly decreased hippocampal caspase-3 ac-
tivity (84% decrease) compared to neonates with ex-
perimentally-induced HI brain injury from dams who
consumed a control beverage.
ese results suggest
PJ has an antioxidant-driven neuroprotective effect
conferred from mother to neonate.
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Alzheimer’s Disease
e neuroprotective properties of pomegran-
ate polyphenols were evaluated in an animal model of
Alzheimer’s disease. Transgenic mice with Alzheimer’s-
like pathology treated with PJ had 50-percent less accu-
mulation of soluble amyloid-beta and less hippocampal
amyloid deposition than mice consuming sugar water,
suggesting PJ may be neuroprotective. Animals also
exhibited improved learning of water maze tasks and
swam faster than control animals.
PFLE (400 or 800 mg/kg/day) given to obese
hyperlipidemic mice for five weeks caused significant
decreases in body weight, percentage of adipose pad
weights, energy intake, and serum cholesterol, triglyc-
eride, glucose, and total cholesterol/HDL ratios. De-
creased appetite and intestinal fat absorption were also
observed, improvements mediated in part by inhibition
of pancreatic lipase activity.
Potential Drug Interactions
Based on pomegranates current popularity
and research suggesting its therapeutic benefit in cancer,
cardiovascular disease, and other diseases treated with
prescription medications, it has been of interest to de-
termine whether pomegranate extracts have any effect
on cytochrome P450-3A, the hepatic enzyme system
responsible for metabolism of many prescription medi-
cations. A randomized, single-dose, crossover study in
Table 3. Ongoing Pomegranate Trials
Rising PSA levels in
men with previous
prostate cancer
Recurrent prostate
Prostate cancer
Benign prostatic
Follicular lymphoma
Rising PSA levels in
men with previous
prostate cancer
Atherosclerosis in
Prevention of
rhino-virus infection
M.D. Anderson Cancer
Center; Houston, TX
Jonsson Comprehensive
Cancer Center; National
Cancer Institute
University of Oslo;
Norwegian Cancer
Society; The Research
Council of Norway
University of California,
Irvine; Jarrow
University of Oslo,
Jonsson Comprehensive
Cancer Center; National
Cancer Institute
HaEmek Medical Center,
Pom Wonderful LLC
300 subjects
102 subjects
20 subjects
45 subjects
250 subjects
10 males
10 females
150 subjects
September 2004
or longer
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13 healthy human volunteers demonstrated PJ pretreat-
ment did not affect elimination half-life or distribution
of intravenous midazolam (a benzodiazepine derivative
with anxiolytic, amnestic, hypnotic, anticonvulsant, and
muscle relaxant properties), nor did it affect the C
clearance of oral midazolam.
is human study con-
tradicts a rat study showing PJ has an inhibitory effect
on carbamazepine pharmacokinetics, an anticonvulsant
medication also metabolized by cytochrome P450-
Safety of Pomegranate Extracts
Pomegranate and its constituents have safely
been consumed for centuries without adverse effects.
Studies of pomegranate constituents in animals at con-
centrations and levels commonly used in folk and tradi-
tional medicine note no toxic effects.
Toxicity of the
polyphenol antioxidant punicalagin, abundant in pome-
granate juice, was evaluated in rats. No toxic effects or
significant differences were observed in the treatment
group compared to controls, which was confirmed via
histopathological analysis of rat organs.
Research in 86 overweight human volunteers
demonstrated the safety of a tableted PFE in amounts
up to 1,420 mg/day (870 mg gallic acid equivalents)
for 28 days, with no adverse events reported or adverse
changes in blood or urine laboratory values observed.
Another study in 10 patients with carotid artery steno-
sis demonstrated PJ consumption (121 mg/L EA
equivalents) for up to three years had no toxic effect
on blood chemistry analysis for kidney, liver, and heart
An explosion of interest in the numerous
therapeutic properties of Punica granatum over the last
decade has led to numerous in vitro, animal, and clini-
cal trials. Pomegranate is a potent antioxidant, superior
to red wine and equal to or better than green tea. In
addition, anticarcinogenic and anti-inflammatory prop-
erties suggest its possible use as a therapy or adjunct
for prevention and treatment of several types of cancer
and cardiovascular disease. Because of pomegranates
antimicrobial properties, it may aid in preventing infec-
tion by dental pathogens, pathogenic E. coli O157:H7,
and antibiotic-resistant organisms such as MRSA.
Pomegranates effect on bacterial pathogens has only
been tested in vitro, however, necessitating human trials
to refute or substantiate any clinical effect. e possibil-
ity that pomegranate extracts may also have an effect
on several other disease processes, such as Alzheimers
disease, osteoarthritis, neonatal brain injury, male infer-
tility, and obesity, underscores the need for more clinical
research. Currently, numerous clinical trials are in pro-
gress exploring the therapeutic potential of pomegran-
ate extracts (Table 3).
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Copyright © 2008 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 13, Number 2 June 2008
Alternative Medicine Review Volume 13, Number 2 2008
Review Article
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Copyright © 2008 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 13, Number 2 June 2008
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results?term=pomegranate. [Accessed on April 21,
... It is believed that the ellagitannin, punicalagin, is the fraction responsible for pomegranate's antibacterial activity. 16 The polyphenol composition of pomegranate arils and skins is characterized by a high proportion of punicalagin, punicalin, ellagitannins, and gallotannins in comparison to ellagic acid. 17 To date, all outspread studies on minor aphthous cannot agree on a definite treatment. ...
... 24 Pomegranate extracts have been proven to remove free radicals and reduce macrophage oxidative stress and lipid peroxidation in animals and to increase plasma antioxidant capacity in elderly humans. 16,25 The antioxidant properties of a pomegranate by-product extract that was made from whole fruit minus the juice have been demonstrated through several studies in rats and mice. ...
... 25 An in vitro analysis of a fermented pomegranate juice extract and a cold pressed seed oil extract reported that the antioxidant capacity of both extracts are higher compared with that of red wine and green tea extract. 16 Another study in rats with CCl 4 -induced liver damage confirmed that pretreatment with pomegranate peel extracts improved or maintained the free-radical scavenging activity of the hepatic enzymes catalase, superoxide dismutase, and peroxidase. The experiment resulted in a 54% reduction in lipid peroxidation values compared to controls, 26 and it was shown that pomegranate pulp (PPJ) has a higher antioxidant property compared to apple juice. ...
Full-text available
Background Herbal drugs are considered alternative agents and have been used for several years around the world. Recurrent aphthous stomatitis (RAS) is one of the most common problems recognized by dentists and skin specialists. This problem is characterized by recurring, painful, small oral mucosal ulcers with a round or oval aspect that mostly appear in keratinized mucosa, cheeks, and on the surface of the mouth under the tongue. Methods In our experiment, the alcoholic and water extracts of Punica granatum var. pleniflora, P. granatum var. Sweet Alak, and P. granatum var. Saveh Black were tested on minor RAS. The study was carried out using the double-blind method. The study population consisted of 210 participants, of whom 69 were females (32%) and 141 were males (68%). In addition to checking several factors, the pain and the degree of the participant's satisfaction had been determined based on visual analog scale. Data analysis was done in the form of a nonparametric method using Kruskal–Wallis test and SPSS version 20 software. Results The results show that the alcoholic and water extracts of P. granatum var. pleniflora have a meaningful therapeutic effect on minor RAS. Results from the antioxidant activity and its relation to total phenolics show that P. granatum var. pleniflora and P. granatum var. Sweet Alak are rich in phenols. Conclusion The water and alcoholic extracts of P. granatum varpleniflora decreased the entire time of complete treatment, and the treatment was meaningfully satisfactory for patients who participated in this experiment.
... Different parts of this plant are used in indigenous Indian medicine to cure various diseases, particularly diabetes [2]. Pomegranate fractions from different parts of the fruit have been linked with the prevention and treatment of a wide range of disorders and diseases, including cardiovascular disease, cancer, Alzheimer disease, erectile dysfunction, male infertility, arthritis, brain ischemia, dental diseases, obesity, and diabetes [3] and [4]. The therapeutic potential of pomegranate fractions is due to the presence of unique bioactive compounds with antioxidant, antiinflammatory, anti-infective, anti-atherogenic, anti-carcinogenic, and anti-hyperglycemic effects [4], [5] and [6]. ...
... Katz and his group concluded that pomegranate extracts and their active compounds could be effective in the treatment and prevention of type 2 diabetes. Later reviews that addressed the therapeutic effects of pomegranate in general [3] or the cardioprotective benefits of pomegranate juice [8] have indirectly discussed the link between pomegranate and diabetes. More recently, a review by Medjakovic and Jungbauer (2013) focused on the potential use of pomegranate and its compounds in therapy for metabolic syndrome [4]. ...
... Punica granatum is an ancient fruit cultivated around the globe from the Mediterranean region to the Himalayas, from Southeast Asia to California and Arizona in the USA. It is known to be used in many traditional systems of medicine for cardiovascular disease, diabetes, bacterial infections, skin damage, arthritis, and obesity along with proven antioxidant, anti-inflammatory, and anticarcinogenic activities [22,23]. ...
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Differently expressed genes (DEGs) across cervical (CC), endometrial (EC), and vulvar carcinoma (VC) may serve as potential biomarkers for these progressive tumor conditions. In this study, DEGs of cervical (CC), endometrial (EC), and vulvar carcinoma (VC) were identified by microarray analysis. The interaction network between the identified 124 DEGs was constructed and analyzed to identify the hub genes and genes with high stress centrality. DEGs, namely, CDK1 and MMP9, were found to show highest degree and highest stress centrality respectively from the gene interaction network of 124 nodes and 1171 edges. DEG CDK1 is found to be overlapping in both cervical and endometrial carcinomic conditions while DEG MMP9 is found in vulvar carcinomic condition. Further, as it is studied that many phytochemicals play an important role as medicinal drugs, we have identified phytochemicals from few widely available medicinal plants and performed comprehensive computational study to identify a multi-targeted phytochemical against the identified DEGs, which are crucially responsible for the progression of these carcinomic conditions. Virtual screening of the phytochemicals against the target DEG protein structures with PDB IDs 4Y72 and 1GKC resulted in identifying the multi-targeted phytochemical against both the proteins. The molecular docking and dynamics simulation studies reveal that luteolin can act as a multi-targeted agent. Thus, the interactional and structural insights of luteolin toward the DEG proteins signify that it can be further explored as a multi-targeted agent against the cervical, endometrial, and vulvar carcinoma.
... In the past decade, numerous studies on the antioxidant, anticarcinogenic, and anti-inflammatory properties of pomegranate constituents have been published, focusing on treatment and prevention of cancer, cardiovascular disease, diabetes, dental conditions, erectile dysfunction, bacterial infections and antibiotic resistance, and ultraviolet radiation-induced skin damage. Other potential applications include infant brain ischemia, male infertility, Alzheimer's disease, arthritis, and obesity (Jurenka, 2008). ...
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Punica granatum (Pg), commonly known as pomegranate is a member of the monogeneric family, Punicaceae. Pg and its chemical components possess various pharmacological and toxicological properties including antioxidant, anti-inflammatory, antifungal and against vegetable and palms diseases. Bayoud is the most dangerous disease, causing significant losses of date palms in Algeria whose the responsible fungi is called Fusarium oxysporum f.sp.albednis. This study focused on the evaluation of the in vitro antifungal activity of a Punica granatum L fruit extracts obtained by the reflux method, considered as a hot method using heating with the following solvents: distilled water, methanol, ethyl acetate, and chloroform; on ten selected strains of Fusarium oxysporum f.sp. albedinis. The evaluation of antifusarial activity of Punica granatum L. was carried out by using the dilution and the direct contact method to determine the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC). The results of the extraction yield show that distilled water and methanol are the two best solvents which give a good yield compared to chloroform and ethyl acetate, 42% for methanol and 54% for distilled water, but the low yield is 0.5% for chloroform and between 1.15 for ethyl acetate. The antifungal activity results of these extracts on the solid and liquid medium, the PDA and the PDB, respectively, show that they have good inhibitory activity against all the tested fungi. According to the results obtained in the solid medium, the extracts tested have an inhibitory activity against Foa, with different MIC values ranging from 1.2 mg/ml to 4.2 mg/ml. The result of growing on liquid medium, shows that with each increase in the concentration of the extracts in the culture medium, there is a decrease in the fungal biomass, and there is a fungicide activity for all extracts used.
... Modern tıbbi araştırmalarda, kanseri, kardiyovasküler hastalığı, diyabeti, Alzheimer hastalığı, kısırlığı tedavi etmede, artrit ve obezitenin yanı sıra ultraviyole (UV) radyasyondan korumada olası kullanımını destekleyen kanıtlar vardır. Pek çok sağlık etkileri nar ve bunlardan yapılan ürünlerdeki çeşitli biyoaktif bileşikler arasındaki sinerjistik etkileşimlerden kaynaklanmaktadır (Jurenka, 2008). Ayrıca, nar özleri içeren takviye edici gıdalar mevcuttur. ...
Background and objectives: The overuse and misuse of antibiotics coupled with the intrinsic and acquired resistance of bacteria resulted in the emergence of multi-drug resistant strains. Pomegranate and Passion fruit are two fruits which have been documented to have signicant antimicrobial activity against harmful organisms which colonize the gut. The present study evaluates the antimicrobial activity of Punica granatum and Passiora edulis against organisms isolated from intestinal infections and compares the antimicrobial efcacy of the ethanolic and aqueous extracts of fruit rind of Punica granatum and leaves of Passiora edulis. Fruit ri Methods: nd of Punica granatum and the fresh leaves of Passiora edulis plants were dried, ground into powder and made into extracts. A total of 100 gastrointestinal pathogens were isolated and included in the study. The antibacterial efcacy of the aqueous and alcoholic extracts against 100 human faecal isolates was tested by employing Kirby Bauer disc diffusion technique. Sensitivity to the ethanolic and aqueous extracts of Punica Results: granatum were found to be maximum in Staphylococcus aureus. MRSA was sensitive to these extracts. Aqueous extract of Punica granatum were effective against a large number of organisms, however, better antimicrobial action was seen with the ethanolic extract of Punica granatum. No encouraging results were obtained with the extracts of Passiora edulis. Our study shows that puried forms of Pomegranate (Punica granat Interpretation and conclusions: um) can be used as an adjunct in the treatment, in conjunction with antibiotics against intestinal pathogens and can open new areas of research.
This paper reports the presence of undeclared drugs in the herbal slimming supplement Sulami®. The four cases of the adverse drug reactions related to Sulami® were reported to the Dutch Pharmacovigilance Centre (Lareb) or the Dutch Poisons Information Centre (DPIC). The analysis of all four collected samples revealed adulteration with sibutramine and canrenone. Both drugs can cause serious adverse drug reactions. From a legal point of view, it is clear that Sulami® does not meet the legal requirement for safety. As defined in the European General Food Law Regulation (GFL) food business operators are responsible for food safety. This also applies to online store owners who sell herbal preparations. Thus, it is clear that it is forbidden to sell Sulami® on the European and Dutch market. Collaboration between involved national authorities make it possible to identify risky products. This allows the nationally responsible regulators to take targeted action. They can call on users to report sell points what makes it possible to arrest the sellers and confiscate the dangerous products. Beyond the national also the European enforcement organizations should take legal measures where possible, to protect public health. The Heads of Food Safety Agencies Working Group on Food Supplements “an Initiative on European level is a good example of efforts to improve consumer safety.
Full-text available
Wound care is a global health issue with a financial burden of up to US $96.8 billion annually in the USA alone. Chronic non-healing wounds which show delayed and incomplete healing are especially problematic. Although there are more than 3000 dressing types in the wound management market, new developments in more efficient wound dressings will require innovative approaches such as embedding antibacterial additives into wound-dressing materials. The lack of novel antibacterial agents and the misuse of current antibiotics have caused an increase in antimicrobial resistance (AMR) which is estimated to cause 10 million deaths by 2050 worldwide. These ongoing challenges clearly indicate an urgent need for developing new antibacterial additives in wound dressings targeting microbial pathogens. Natural products and their derivatives have long been a significant source of pharmaceuticals against AMR. Scrutinising the data of newly approved drugs has identified plants as one of the biggest and most important sources in the development of novel antibacterial drugs. Some of the plant-based antibacterial additives, such as essential oils and plant extracts, have been previously used in wound dressings; however, there is another source of plant-derived antibacterial additives, i.e., those produced by symbiotic endophytic fungi, that show great potential in wound dressing applications. Endophytes represent a novel, natural, and sustainable source of bioactive compounds for therapeutic applications, including as efficient antibacterial additives for chronic wound dressings. This review examines and appraises recent developments in bioactive wound dressings that incorporate natural products as antibacterial agents as well as advances in endophyte research that show great potential in treating chronic wounds.
p> The purpose of this research is to present scientific information related to madura’s herbal medicine “empot super” and herbal extract made from existing composition of the various constituent plants of empot super. Then, this research spesifically detects antioxidants activity found in herbal medicine and herbal extract expected to provide a scientific assurance either for the industry or the consumen.Samples used in this research are madura’s herbal medicine and herbal extract mixture of various simplisia those are used in the manufacture of empot super herbal medicine. To get those samples, herbal medicine is imported from madura, while the herbal extract is the production of extraction process by using ethanol. The samples are subsequently assay the antioxidants activity by using DPPH method at 571nm.The final result of this research indicates the existance of IC<sub>50</sub> proportion in herbal medicine that is 34,11mg/ml and 45,44mg/ml in herbal extract. Indeed, in the assay of herbal medicine and herbal extract classified as having a very strong antioxidants activity</em
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Statement of the problem: Natural products have attracted interest as an alternative to synthetic medi-cations for the treatment of oral diseases due to their efficacy and safety. Propolis and pomegranate extracts have both demonstrated efficacy for the treatment of denture stomatitis. However, use of the two compounds together has not been tested for this purpose. Purpose: A comparison was made of the efficacy of a commercially available propolis-pomegranate buccal spray formulation for the treatment of denture stomatitis, compared with miconazole gel, based on stomatitis lesions and Candida spp. concentrations in mouth rinses. Materials and method: This was an experimental study, characterized as an open-label, parallel two-armed, non-inferiority randomized clinical trial. Forty elderly adults aged < 60 years with denture stoma-titis were randomly allocated to two groups. The patients applied a buccal spray containing 0.5% propo-lis and 0.9% pomegranate extracts or 2% miconazole gel, a standard treatment recommended in Brazil, to the inner surface of their dentures three times a day for 14 days. They were examined at days 1, 7, 14 and stomatitis lesions were categorized according to Newton's score. Mouth rinses were made with saline solution at days 1 and 14 and then assessed for Candida spp. Results: Both treatments reduced the Newton's score, with clinical cure rates of 75 and 40% for the miconazole and propolis-pomegranate groups, respectively. The Candida concentrations in the mouth rinse decreased significantly only in the miconazole group. Conclusion: The propolis-pomegranate spray was less effective than the miconazole treatment. Howev-er, clinical improvement was also observed in patients treated with the propolis-pomegranate buccal spray.
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The aim of this study was to evaluate the use of a gel containing the extract of Punica granatum as an antifungal agent against candidosis associated with denture stomatitis. Sixty patients with denture stomatitis confirmed by clinical and mycologic examination were selected. The patients were randomly allocated in two groups of 30 individuals each according to the medication prescribed: group A used miconazole (Daktarin(R) gel oral) and group B used a gel of P. granatum Linne (pomegranate). Both groups used the medicines three times per day for 15 days. Forty-eight hours after finishing the treatment the patients were re-examined and a second set of samples was collected for mycologic examination. The medicines were evaluated for their clinical response and negativity for Candida. The clinical results showed a satisfactory and regular response in 27 and 21 subjects of groups A and B, respectively. Negativity of yeasts was observed in 25 subjects of group A and 23 of group B. It can be concluded that the extract of P. granatum may be used as a topical antifungal agent for the treatment of candidosis associated with denture stomatitis.
The alkaloid patterns of different bark samples of Punica granatum from Yugoslavia have been studied. In addition to the known alkaloids pelletierine, N-methylpelletierine and pseudopelletierine ten further alkaloids could be detected by capillary GLC-M.S. Some of these are the 2- and 2,6-substituted alkaloids sedridine, 2-(2'-hydroxypropyl)Δ1-piperidine, 2-(2'-propenyl) Δ1-piperidine and norpseudopelletierine. The pyrrolidine alkaloids hygrine and norhygrine were only found in the root bark. The necessity for verifying the quality of the pomegranate bark as an anthelmintic drug is discussed
The structures of punicalin and punicalagin, isolated from the bark of Punica granatum L. (pomegranate), have been revised to 4, 6-(S, S)-gallagyl-D-glucose (1) and 2, 3-(S)-hexahydroxy-diphenoyl-4, 6-(S, S)-gallagyl-D-glucose (2), respectively, on the basis of chemical and spectroscopic evidence. In addition, a new hydrolyzable tannin, 2-O-galloyl-4, 6-(S, S)-gallagyl-D-glucose (3) was isolated from the same plant source, and characterized.
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.
Hypoglycaemic drugs are either too expensive or have undesirable side effects including hematological, coma and disturbances of liver and kidney. Limiting of diabetes without any side effects is still a challenge to the medical system. This leads to exert effort to search for effective, safer and less cost antidiabetic plants. This investigation aims to evaluate the role of Punica granatum powder peels extract in its human therapeutic dose on beta cell numbers blood glucose and plasma insulin levels in normal and alloxan diabetic rats for 4-weeks of treatment. The treatment revealed that pomegranate aqueous extract significant decreased blood glucose and increased insulin levels in normal and diabetic treated rats. Pancreas showed increased number of beta cells in normal and treated diabetic rats. In conclusion pomegranate peel aqueous extract can reduce blood sugar through regeneration of ß cells.