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Accumulating data clearly claimed that Punica granatum L. (pomegranate) has several health benefits. Pomegranates can help prevent or treat various disease risk factors including high blood pressure, high cholesterol, oxidative stress, hyperglycemia, and inflammatory activities. It is demonstrated that certain components of pomegranate such as polyphenols have potential antioxidant, anti-inflammatory, and anticarcinogenic effects. The antioxidant potential of pomegranate juice is more than that of red wine and green tea, which is induced through ellagitannins and hydrosable tannins. Pomegranate juice can reduce macrophage oxidative stress, free radicals, and lipid peroxidation. Moreover, pomegranate fruit extract prevents cell growth and induces apoptosis, which can lead to its anticarcinogenic effects. In addition, promoter inhibition of some inflammatory markers and their production are blocked via ellagitannins. In this article, we highlight different studies on the therapeutic effects of pomegranate and their suggested mechanisms of actions.
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Advanced Biomedical Research | 2014 1
Accumulating data clearly claimed that Punica granatum L. (pomegranate) has several health benefits.
Pomegranates can help prevent or treat various disease risk factors including high blood pressure, high
cholesterol, oxidative stress, hyperglycemia, and inflammatory activities. It is demonstrated that certain
components of pomegranate such as polyphenols have potential antioxidant, anti‑inflammatory, and
anticarcinogenic effects. The antioxidant potential of pomegranate juice is more than that of red wine and
green tea, which is induced through ellagitannins and hydrosable tannins. Pomegranate juice can reduce
macrophage oxidative stress, free radicals, and lipid peroxidation. Moreover, pomegranate fruit extract
prevents cell growth and induces apoptosis, which can lead to its anticarcinogenic effects. In addition,
promoter inhibition of some inflammatory markers and their production are blocked via ellagitannins. In
this article, we highlight different studies on the therapeutic effects of pomegranate and their suggested
mechanisms of actions.
Key Words: Antioxidant, inflammatory activities, pomegranate
Address for correspondence:
Dr. Sedigheh Asgary, Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Instute, Isfahan University of Medical Sciences, Isfahan, Iran.
E‑mail: sasgary@yahoo.com
Received: 28.09.2012, Accepted: 13.11.2012
Abstract
Potent health effects of pomegranate
Aida Zarfeshany, Sedigheh Asgary1, Shaghayegh Haghjoo Javanmard
Physiology Research Center, 1Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Instute, Isfahan, Iran
Review Report
is Punica, with one predominant species called
P. granatum.[2]
The trees can grow up to 30 feet in height. The leaves
are opposite, narrow, oblong with 3‑7 cm long and
2cmbroad.Ithasbrightred,orange,orpinkowers,
whichare 3cmindiameter withfourtove petals.
Edible fruit has a rounded hexagonal shape, with
5‑12 cm in diameter and weighing 200 g. The thick
skin surrounds around 600 arils, which encapsulates
the seeds.[3]
CHEMICAL COMPOSITION
Seed
About 18% of dried and cleaned white seeds are oil.
The oil is rich in punicic acid (65%), which is a triple
conjugated 18‑carbon fatty acid [Figure 1]. There are
some phytoestrogen compounds in pomegranate seeds
INTRODUCTION
Punica granatum L. (Pomegranate) is a long‑lived
and drought‑tolerant plant. Arid and semiarid
zones are popular for growing pomegranate trees.
They are widely cultivated in Iran, India, and the
Mediterranean countries such as Turkey, Egypt,
Tunisia, Spain, and Morocco.[1] However, pomegranate
is categorized as a berry but it belongs to its own
botanical family, Punicaceae. The only genus
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How to cite this article: Zarfeshany A, Asgary S, Javanmard SH. Potent health effects of pomegranate. Adv Biomed Res 2014;3:100.
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Zarfeshany and Asgary: Pomegranate health effects
2 Advanced Biomedical Research | 2014
that have sex steroid hormones similar to those in
humankind. The 17‑alpha‑estradiol is a mirror‑image
version of estrogen.[3]
Juice and peel
Pomegranate juice is a good source of fructose, sucrose,
and glucose. It also has some of the simple organic
acids such as ascorbic acid, citric acid, fumaric acid,
and malic acid. In addition, it contains small amounts
of all amino acids, specically proline, methionine,
and valine. Both the juice and peel are rich in
polyphenols. The largest classes include tannins and
avonoids [Figure 2] that indicate pharmacological
potential of pomegranate due to their strange
antioxidative and preservative activities.[3]
Ellagitannin is a type of tannins; it can be broken
down into hydroxybenzoic acid such as ellagic acid.
It is widely used in plastic surgeries, which prevents
skin flap’s death due to its antioxidant activity.
Two other ellagitannins that are found in both
pomegranate juice and peel are punicalagin and
punicalin.Severalclassesofpomegranateavonoids
include anthocyanins, avan 3‑ols, and avonols.
Pomegranate juice and peel have catechins with a high
antioxidant activity. They are essential compounds
of anthocyanin’s production with antioxidant and
inammatoryrole.Anthocyaninscausetheredcolorof
juice, which is not found in the peel. All pomegranate
avonoids show antioxidant activity with indirect
inhibition of inammatory markers such as tumor
necrosis factor‑alpha (TNF‑α).[3]
Bark and roots
The pomegranate tree’s bark and roots are rich sources
of chemicals called alkaloids. They are carbon‑based
substances; they were used to treat worms in the
human gastrointestinal tract in traditional medicine.[3]
Table 1 Shows pomegranate’s nutrient values for 100 g
of raw edible portion[4]
Health effects
Prostate cancer
After lung cancer, the second leading cause of male
cancer death is prostate cancer worldwide. Its
progress before onset of symptoms is slow; therefore,
pharmacological and nutritional interventions could
affect the quality of patient’s life by delaying its
development.[5]
It was shown that pomegranate fruit could be used
in the treatment of human prostate cancer because it
could inhibit cell growth and induce apoptosis.[6] It leads
to induction of pro‑apoptotic proteins (Bax and Bak)
and downregulation of anti‑apoptotic proteins (Bcl‑xL
and Bcl‑2).[6] Moreover, the presence of NFκB and cell
viability of prostate cancer cell lines has been inhibited
when using pomegranate fruit extract, because it
blocks NFκB.[7] Polyphenols of fermented juice and
pomegranate oil can inhibit the proliferation of LNCaP
Table 1: Pomegranate’s nutrient values for 100 g of raw edible
portion
Nutrients Units Value per 100 g
Water g 77.93
Energy Kcal 83
Protein g 1.67
Total lipid (fat) g 1.17
Ash g 0.53
Carbohydrates g 18.70
Fiber g 4.0
Sugars, total g 13.67
Calcium Mg 10
Iron Mg 0.3
Magnesium Mg 12
Phosphorus Mg 36
Potassium Mg 236
Sodium Mg 3
Ascorbic acid, total Mg 10.2
Choline, total Mg 7. 6
Adapted from united states department of agriculture (USDA) National nutrient
database for standard reference
Figure 1: Chemical structure of punicic acid (9Z,11E,13Z-octadeca-
9,11,13-trienoic acid)
Figure 2: (a) Flavone backbone (2-phenyl-1, 4-benzopyrone). (b) Tannic acid
b
a
Zarfeshany and Asgary: Pomegranate health effects
Advanced Biomedical Research | 2014 3
(epithelial cell line derived from a human prostate
carcinoma), PC‑3, and DU145 human prostate cancer
cell lines. These effects were the result of changes in
cell cycle distribution and apoptosis induction.[6] In
addition, it is reported that pomegranate fruit extract
oral administration in nude mice implanted with
androgen‑sensitiveCWR22RV1cellscausedsignicant
decrease in serum prostate‑specic antigen (PSA)
level and inhibited tumor growth.[7] Besides, the
observed increase in NFκB activity during androgen
dependence to androgen independence transition in
the LAPC4xenograft model was terminated.[8]
Breast cancer
Fermented pomegranate juice has double the
antiproliferative effect compared to fresh pomegranate
juice in human breast cancer cell lines MCF‑7 (breast
cancer cell line isolated in 1970 from a 69‑year‑old
Caucasian woman) and MB‑MDA‑231. In addition,
pomegranate seed oil caused 90% prevention of
proliferation of MCF‑7 cells.[9,10]
Lung cancer
Pomegranate fruit extract can inhibit several
signaling pathways, which can be used in the
treatment of human lung cancer. Pathways include
Mitogen‑activated protein kinases (MAPK) PI3K/Akt
and NFκB. In addition, there was a 4 day delay in the
appearance of tumors (from 15 to 19 days) in mice
implanted with A549 cells.[10] These studies indicate
the chemopreventive effects of pomegranate fruit
extract.[3]
Colon cancer
Adams et al.[11]havereportedtheanti‑inammatory
effects of pomegranate juice on the signaling proteins
in HT‑29 human colon cancer cell line. Reduction
in phosphorylation of the p65 subunit of NFκB, its
binding to the NFκB response, and 79% inhibition in
TNF‑α protein expression have been observed with
50 mg/L concentration of pomegranate extract.
Skin cancer
It has been demonstrated that pomegranate oil has
chemopreventive efcacy in mice. Reduced tumor
incidence (7%), decrease in tumor numbers, reduction
in ornithine decarboxylase (ODC) activity (17%),
signicantinhibitioninelevatedTissueplasminogen
activator (TPA)‑mediated skin edema and hyperplasia,
protein expression of ODC and COX‑2, and epidermal
ODC activity have been reported with pomegranate
oil treatments.[12,13] Pomegranate extract in various
concentrations (5‑60 mg/L) was effective against UVA‑
and UVB‑induced damage in SKU‑1064 broblast
cells of human, which was relevant in reducing
NFκB transcription, downregulating proapoptotic
caspase‑3, and elevating the G0/G1 phase associated
with deoxyribonucleic acid (DNA) repair.[14]
Cardiovascular diseases
Pomegranate juice is an affluent source of
polyphenols with high antioxidative potential.
Moreover, its antiatherogenic, antihypertensive, and
anti‑inammatoryeffectshavebeenshowninlimited
studies in human and murine models.[15]
Hypertension is the most common disease in
primary care of patients. It is found in comorbidity
with diabetes and cardiovascular disease, and the
majority of patients do not tend to be medicated.
Pomegranate juice prevents the activity of serum
angiotensin‑converting enzyme and reduces systolic
blood pressure.[16] Angiotensin II acute subcutaneous
administration causes increased blood pressure
in diabetic Wistar rats. It has been shown that
pomegranate juice administration (100 mg/kg)
for 4 weeks could reduce the mean arterial blood
pressure.[17] Pomegranate juice consumption resulted
in 30% decrease in carotid intima‑media thickness
after 1 year. The patient’s serum paraoxonase 1
(PON 1) activity showed 83% increase, whereas both
serum low dwnsity lipoprotein (LDL) basal oxidative
stateandLDLsusceptibilitytocopperionsignicantly
decreased by 90% and 95%, respectively.[18]
Punicic acid, which is the main constituent of
pomegranate seed oil, has antiatherogenic effects. In
a study on 51 hyperlipidemic patients, pomegranate
seed oil was administered twice a day (800 mg/day)
for 4 weeks. There was a significant decrease in
triglycerides (TG) and TG: High density lipoprotein
(HDL) cholesterol ratio by 2.75 mmol/L and 5.7 mmol/L,
respectively, whereas serum cholesterol, LDL‑C, and
glucose concentration remained unchanged.[19]
High plasma LDL concentration is the major risk factor
for atherosclerosis. Therefore, LDL modications,
including oxidation, retention, and aggregation, play
a key role in atherosclerosis as well. Studies have
shown that consuming pomegranate juice for 2 weeks
resulted in declined retention and aggregation of
LDL susceptibility and increased activity of serum
paraoxonase (a protective lipid peroxidation esterase
related to HDL) by 20% in humans. Pomegranate juice
administration in mice for 14 weeks showed reduced
LDL oxidation by peritoneal macrophages by more
than 90%, which was because of reduced cellular lipid
peroxidation and superoxide release. The uptake of
oxidized LDL showed 20% reduction in mice. The
size of atherosclerotic lesions reduced by 44% after
pomegranate juice supplementation.[20] Moreover,
pomegranate juice administration to apolipoprotein
Zarfeshany and Asgary: Pomegranate health effects
4 Advanced Biomedical Research | 2014
E‑decient mice with advanced atherosclerosis for
2 months reduced oxidized LDL (31%) and increased
macrophagecholesterolefux(39%).[21]
In cultured human endothelial cells and
hypercholesterolemic mice, both pomegranate juice
and fruit extract reduced the activation of ELK‑1 and
p‑CREB (oxidation‑sensitive responsive genes) and
elevated the expression of endothelial nitric oxide
synthase. It is suggested that polyphenolic antioxidant
compounds in pomegranate juice are responsible for
the reduction of oxidative stress and atherogenesis.[22]
In another study,[23] concentrated pomegranate juice
was shown to reduce heart disease risk factors.
Administration of concentrated pomegranate juice
to 22 diabetic type 2 patients with hyperlipidemia
couldsignicantlyreduceTC,LDL‑C,LDL‑C:HDL‑C
ratio, and TC: HDL‑C ratio. However, it was unable to
decrease serum TG and HDL‑C concentrations.
Oraladministrationof pomegranateoweraqueous
extract in streptozotocin (STZ)‑induced albino Wistar
rats in both 250 mg/kg and 500 mg/kg doses for
21days couldsignicantlyreduce brinogen(FBG),
TC, TG, LDL‑C, and tissue lipid peroxidation level
and increased the level of HDL‑C and glutathione
content.[24]
Heartbrosisincreasesamongdiabetics,whichresults
in impairing cardiac function. Endothelin (ET)‑1 and
NFκB are interactive fibroblast growth regulators.
It is suggested that pomegranate flower extract
(500 mg/kg/day) in Zucker diabetic fatty rats could
reduce the ratios of van Gieson‑stained interstitial
collagen deposit area to a total left ventricular area and
perivascular collagen deposit areas to coronary artery
mediaareaintheheartanddiminishescardiacbrosisin
theserats.Inaddition,overexpressedcardiacbronectin
and collagen I and II messenger RNAs (mRNAs) were
inhibited. It also decreased the upregulated cardiac
mRNA expression of ET‑1, ETA, inhibitor‑κBβ, and
c‑jun.Pomegranateowerextractisadualactivatorof
peroxisome proliferator‑activated receptor (PPAR)‑α and
γ and improves hyperlipidemia, hyperglycemia, and fatty
heart in diabetic fatty Zucker rats.[25,26]
Punicic acid caused a dose‑dependent increase
in PPAR alpha and gamma reporter activity in
3T3‑L1 cells. Dietary punicic acid reduced plasma
glucose, suppressed NFκB activation and unregulated
TNF‑α expression and PPAR‑α/γ responsive genes in
adipose tissue and skeletal muscle.[27]
Pomegranate leaf extract was administered (400 and
800 mg/kg/day) to high‑fat‑diet‑induced obese and
hyperlipidemic mouse models for 5 weeks. The results
indicatedsignicantreductioninbodyweight,energy
intake (based on food intake), serum total cholesterol
(TC), TG, FBG, and TC/HDL‑C ratio. Intestinal fat
absorption was inhibited as well.[28]
The high fat diet (HFD) with 1% pomegranate seed
oil (rich source of punicic acid) was administered for
12 weeks to induce obesity and insulin resistance in
mice. The pomegranate seed oil‑fed group exhibited
lower body weight (4%) and body fat mass (3.1%)
compared with only HFD‑fed mice. A clear improvement
was observed in peripheral insulin sensitivity (70%) in
pomegranate seed oil‑administered rats.[29]
Fatty liver is the most common abnormal liver
function among diabetics. Pomegranate ower was
examined for its antidiabetic effects on diabetic type II
and obese Zucker rats. Rats fed with 500 mg/kg/day
of pomegranate ower extract for 6 weeks showed
decreased ratio of liver weight to tibia length, lipid
droplets, and hepatic TG contents. In addition, it
increased PPRA‑α and Acyl‑COA oxidase mRNA levels
in HepG2 cells.[30]
In a study by de Nigris et al.,[31] they compared
the influence of pomegranate fruit extract with
pomegranate juice on nitric oxide and arterial function
in obese Zucker rats. They have demonstrated that
bothpomegranatefruitextractandjuicesignicantly
reducedthevascularinammatorymarkersexpression,
thrombospondin, and cytokine TGFP 1. Increased
plasma nitrite and nitrate were observed with
administration of either pomegranate fruit or juice.
Many studies have reported the anti‑inammatory
potential of pomegranate extract. In a study on 30
Sprague‑Dawley rats with acute inammation due
to myringotomy, it was observed that 100 μl/day
of pomegranate extract could signicantly reduce
reactive‑oxygen species (ROS) levels. The extract was
administered 1 day before and 2 days after surgery.
Reduced thickness of lamina propria and vessel
density was reported as well.[32] Both ellagitannins and
ellagic acid are the main components of pomegranate
extract, which have anti‑inammatory properties.
They are metabolized by gut microbiota to yield
urolithins. It is suggested that urolithins are the main
components responsible for the anti‑inammation
properties of pomegranate. It is suggested that
NFκB activation, MAPK downregulation of COX‑2,
and mPGES‑1 expression were inhibited through a
decrease in PGE2 production.[33] Neutrophils play
key roles in inflammatory processes by releasing
great amounts of ROS generated by NADPH‑oxidase
and myeloperoxidase. It is indicated that punicic
Zarfeshany and Asgary: Pomegranate health effects
Advanced Biomedical Research | 2014 5
acidexhibitedapotent anti‑inammatory effect via
prevention of TNF‑α‑induced priming of NADPH
oxidase by targeting the p38MAPKinase/Ser 345‑p
47 phox‑axis and releasing MPO.[34] Hyperglycemia
results in oxidative stress in diabetes mellitus, which
is a major factor in the pathogenesis of cardiovascular
disease. Results suggested that pomegranate extract,
owing to its polyphenol‑rich antioxidants (oleanolic,
ursolic, and gallic acids), could prevent cardiovascular
complications through decrease in LDL, increase in
HDL, serum paraoxonase 1 stability and activity, and
nitric oxide production.[35‑37]
Osteoarthritis
The most common forms of arthritis are osteoarthritis
and its major progressive degenerative joint disease,
which could affect joint functions and quality of
life in patients. It is mediated by proinammatory
cytokines such as IL‑1 and TNF‑α. MAPKs are
important due to their inammatory and cartilage
damage regulation.[38] P38‑MAPKs are responsible for
regulating cytokine production, neutrophils activation,
apoptosis, and nitric oxide synthesis. The MAPK family
phosphorylates a number of transcription factors such
as runt‑related transcription factor‑2 (RUNX‑2).[39‑41]
Pomegranate extract, with its rich source of
polyphenols, can inhibit IL‑1 β‑induced activation of
MKK3, DNA‑binding activity of RUNX‑2 transcription
factor, and p38 α‑MAPK isoform.[38]
Rheumatoid arthritis
Rheumatoid arthritis is an autoimmune disease
that affects 0.5‑1% of people worldwide. Women are
afictedmorethanmen.Thisinammatorydiseaseis
characterizedbyinammationandboneerosion.[38,39]
Critical mediators in the pathogenesis of rheumatoid
arthritis are TNF‑α, IL‑1 β, MCP1, Inducible nitric
oxide synthase (iNOS), and COX‑2‑agents, which are
stimulated by p38‑MAPK and NFκB activation.[42,43]
It is shown that pomegranate extract could reduce
the onset and incidence of collagen‑induced arthritis
inmice.Severityofarthritis,jointinammation,and
IL‑6levelweresignicantlyreducedinpomegranate
extract‑fed mice.[44]
Antimicrobial/fungal effect
Since bacterial resistance to antimicrobial
drugs is increasing, medicinal plants have been
considered as alternative agents. Pomegranate
has been widely approved for its antimicrobial
properties.[4,45,46] It has been shown that dried
powder of pomegranate peel has a high inhibition
of Candida albicans.[47] In addition, antimicrobial
effects of both methanol and dichloromethane
pomegranate extracts have been demonstrated on
the Candida genus yeast as pathogen‑causing disease
in immunosuppressive host.[48] Methicillin‑resistant
staphylococcus aureus (MRSA) and methicillin‑sensitive
staphylococcus aureus (MSSA) (multiple antibiotics
resistant) produce panta valentine leukocidin (PVL)
toxin, which can lead to higher levels of morbidity
and mortality.[49,50] It is indicated that a combination
of pomegranate peel extract with Cu (II) ions exhibit
enhanced antimicrobial effects against isolated MSSA,
MRSA, and PVL.[51] One of the leading etiological
bacteria of urinary tract infections is Escherichia Coli.
Strong antibacterial activity of ethanol extract against
E. coli has been shown.[52]
Skin
Solar ultraviolet radiations are the primary causes of
many biological effects such as photoaging and skin
cancer. These radiations resulted in DNA damage,
protein oxidation, and matrix metalloproteinases
induction. In one study, the effects of pomegranate
juice, extract, and oil were examined against
UVB‑mediated damage. These products caused a
decrease in UVB‑induced protein expression of c‑Fos
and phosphorylation of c‑Jun.[53] On the other hand,
productionofproinammatorycytokinesIL‑1β and IL‑6
was decreased by topical application of 10 micromol/L
of ellagic acid. The inflammatory macrophages
inltrationwasblockedintheintegumentsofSKH‑1
hairless UVB‑exposed mice for 8 weeks.[54]
Dental effects
The interbacterial coaggregations and these bacterial
interactions with yeasts are related to the maintenance
of oral microbiota. It is indicated that dried, powdered
pomegranate peel shows a strong inhibition of
C. albicans with a mean zone of 22 mm.[55] In another
study, the antiplaque effect of pomegranate mouth
rinse has been reported.[56] In addition, hydroalcoholic
extract of pomegranate was very effective against
dental plaque microorganisms (84% decrease
(cfu/ml)).[57]
Reproductive system
One of the main constituents (16%) of the methanolic
pomegranate seed extract is beta‑sitosterol. It is
suggested that the extract is a potent phasic activity
stimulator in rat uterus, which happens due to the
non‑estrogenic effects of beta‑sitosterol on inhibiting
sarco‑endoplasmic reticulum Ca2+‑ATPase (SERCA)
and K channel, which resulted in contraction by
calcium entry on L‑type calcium channels and myosin
light chain kinase (MLCK).[58] It is demonstrated
that pomegranate fruit extract has an embryonic
protective nature against adrianycin‑induced oxidative
stress (adrianycin is a chemotherapeutic drug used
Zarfeshany and Asgary: Pomegranate health effects
6 Advanced Biomedical Research | 2014
in cancer treatment).[59] Moreover, pomegranate
juice consumption could increase epididymal sperm
concentration, motility, spermatogenic cell density,
diameter of seminiferous tubules and germinal cell
layer thickness.[60]
Alzheimer
Hartman et al.[61] showed that mice treated by
pomegranate juice have 50% less soluble Abeta
42 accumulation and amyloid deposition in the
hippocampus, which could be considered for Alzheimer’s
disease improvement.
Malaria
In the presence of pomegranate fruit rind, the
induced MMP‑9 mRNA levels by haemozoin or
TNF was decreased, which may be attributed to
the antiparasitic activity and the inhibition of the
proinammatorymechanismsresponsibleintheonset
of cerebral malaria.[62,63]
HIV
The anti‑HIV‑1 microbicide of pomegranate juice
blocks virus binding to CD4 and CXCR4/CCR5,
thereby preventing infection by primary virus clades
A to G and group O.[64]
Wound healing
Use of pomegranate extract and flower showed
signicant reduction in wound area and increased
thewell‑organizedbandsofcollagen,broblasts,and
few inammatory cells.[65,66] Properties of elevated
wound contraction and the period of epithelialization,
collagen, and protein synthesis were reported in
hydroalcoholic pomegranate extract.[67]
Mechanisms of action
Pomegranate can induce its beneficial effects
through its various metabolites. The antioxidant and
antiatherosclerotic potentials of pomegranate are
mainly relevant to the high polyphenol concentrations
in pomegranate fruit such as ellagitannins and
hydrolysable tannins.[68] COX‑1 and COX‑2 enzymes
and IL‑1 β activity can be inhibited by pomegranate
fruit extract.[69]
It is suggested that pomegranate can antagonize
the stimulation of mRNA of MMP‑9 in THP‑1/
monocytes. The whole fruit and compounds inhibit
TNF‑induced MMP‑9 promoter activity.[41] Urolithins
are metabolites that are metabolized by the human
intestinal microora. These compounds decreased
MMP‑9 sretion and mRNA levels induced by HZ or
TNF. It is suggested that ellagitannins are responsible
for the control of excessive production of MMP‑9, which
could result in decreased production of noxious cytokine
TNF.[70] TNF cytokines promote NFκB binding to target
sequences while inducing transcription of several genes
such as the MMP‑9 gene.[71] Ellagitannins prevent NFκB
promoter activity by blocking NFκB‑driven transcription
and affecting the entire cytokine cascade. Ellagitannins
inhibittheactivationofinammatorypathwayssuchas
MAPK.[40] In addition, pomegranate compounds could
inhibit angiogenesis through the downregulation of
vascular endothelial growth factor in cancers.[4]
Drug interactions involving pomegranate
Therapeuticbenetsofpomegranateinvariousdiseases
would lead to an increase in its consumption.[72] It is
important that pomegranate consumption does not affect
the oral bioavailability of drugs.[73]
A study on human liver microsomes has shown the
inhibitory effect of pomegranate juice on CYP2CP
(a gene that codes for an enzyme to break down
warfarin in the body) and increased bioavailability
of tolbutamide (substrate for CYP2CP) in rats.
Moreover, it is suggested that pomegranate may inhibit
cytochrome P450‑3A (CYP3A)‑mediated carbamazepine
metabolism.[4,74,75]
Pomegranate safety
Many studies have been carried out on the different
components derived from pomegranate but no adverse
effects have been reported in the examined dosage.
Histopathological studies on both sexes of OF‑1 mice
confirmed the non‑toxic effects of the polyphenol
antioxidant punicalagin. Besides, in a study on 86
overweight human subjects who received 1420 mg/day
of pomegranate fruit extract in tablet form for 28 days,
no side effects or adverse changes in urine or blood of
individuals were reported.[4,76]
Products and supplementation
Apart from fruit, pomegranate is available in various
forms such as bottled juice (fresh or concentrated),
powdered capsules, and tablets, which are derived from
seed, fermented juice, peel, leaf and ower, gelatin
capsules of seed oil extracts, dry or beverage tea from
leaves or seeds, and other food productions such as jams,
jellies, sauces, salad dressings, and vinegars. Anardana,
which is the powdered form of pomegranate seed, is used
as a form of spice.[3]
CONCLUSION
Pomegranate is a potent antioxidant. This fruit is rich
inavonoids,anthocyanins,punicicacid,ellagitannins,
alkaloids, fructose, sucrose, glucose, simple organic
acids, and other components and has antiatherogenic,
antihypertensive, and anti‑inammatory properties.
Pomegranate can be used in the prevention and
Zarfeshany and Asgary: Pomegranate health effects
Advanced Biomedical Research | 2014 7
treatment of several types of cancer, cardiovascular
disease, osteoarthritis, rheumatoid arthritis, and other
diseases. In addition, it improves wound healing and is
benecialtothereproductivesystem.Pomegranatecan
induceitsbenecialeffectsthroughtheinuenceofits
various bioavailable constituents and metabolites on
gene expression. Although many in vitro, animal and
clinical trials have been carried out to examine and
prove the therapeutic effects of these compounds, further
human trials and studies are necessary to understand
the therapeutic potentials of pomegranate.
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... Page 2 of 12 Husain and Ahmad The Journal of Basic and Applied Zoology (2024) 85:37 on gene expression (Husain et al., 2018;Zarfeshany & Asgary, 2014). Studies have shown that they have several compounds beneficial for human beings that may possibly lower the risk of various diseases such as cancer, cardiovascular diseases, skin, osteoarthritis, rheumatoid arthritis, malaria, and wound healing (Wang et al., 2018;Zarfeshany & Asgary, 2014). ...
... Page 2 of 12 Husain and Ahmad The Journal of Basic and Applied Zoology (2024) 85:37 on gene expression (Husain et al., 2018;Zarfeshany & Asgary, 2014). Studies have shown that they have several compounds beneficial for human beings that may possibly lower the risk of various diseases such as cancer, cardiovascular diseases, skin, osteoarthritis, rheumatoid arthritis, malaria, and wound healing (Wang et al., 2018;Zarfeshany & Asgary, 2014). Due to the presence of hydrolysable tannins, anthocyanins and ellagic acid derivatives, higher antioxidant activity was exhibited by Pomegranate juice (PGJ) in comparison with that of green tea and red wine (Gil et al., 2000). ...
... Due to the presence of hydrolysable tannins, anthocyanins and ellagic acid derivatives, higher antioxidant activity was exhibited by Pomegranate juice (PGJ) in comparison with that of green tea and red wine (Gil et al., 2000). Flavonoids present in PGJ have the ability of scavenging the reactive oxygen radicals and show antioxidant activity via inhibi ting inflammatory markers like TNF-α (Moneim et al., 2013;Zarfeshany & Asgary, 2014;Colombo et al., 2013). Further, PGJ displayed a protective effect on the liver and showed the antifibrotic power in restraining the prevalence of liver fibrogenesis in rodents (Husain et al., 2018;Ibrahim et al., 2016). ...
Article
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Background Pomegranate is considered as one of the oldest elixirs having various properties. Renal fibrosis is a preliminary sign of pathological degradation in most ailments related to kidney. Several efforts have been made for the discovery of cost-effective and safe therapeutics for the alleviation of renal diseases. There is a major dearth of studies on the action of pomegranate juice (PGJ) against NDEA-instigated kidney injury. This study investigates the protective and antifibrotic action of PGJ in restricting the occurrence of experimental renal fibrosis in Wistar rats. Renal injury was generated by a single intraperitoneal dose of 10 ml kg ⁻¹ b.wt. (1% NDEA stock), while fresh PGJ (i.p.) in doses of 2 ml kg ⁻¹ b.wt was administered thrice a week on alternate days for two weeks to observe amelioration. The renal function indices (blood urea, creatinine, and uric acid), SOD, CAT, LPO levels and renal anatomy (H&E, MT, Picrosirius and SEM) were investigated. Results The assessment of renal function demonstrates augmented levels of blood urea, creatinine and uric acid in NDEA-administered groups in comparison with controls. SOD, CAT declined significantly in NDEA Day-7- and Day-14-treated animals, while the MDA levels raised by ~ 70.5% and ~ 76.3% in these groups, respectively. However, supplementation of PGJ provided recuperation from these elevated levels in injured groups. H&E staining of the controls exhibited normal renal structure with intact glomerulus and Bowman’s capsule, while NDEA generated congestion of glomerular tuft, convoluted tubules with cloudy swelling and multiple subsidence of the renal tissue. Noticeable presence of collagen fibers in the interstitium of cortex region of kidney was observed by MT staining along with gross ultrastructural deterioration in NDEA-administered animals by electron microscopy. PGJ supplementation exhibited restoration of renal anatomy and physiology. Conclusions Pomegranate may be considered as a potent nutraceutical to prevent NDEA-induced renal damage and may be included as a daily dietary supplement.
... The mechanisms of anti-inflammatory and anticancer effects of numerous compounds in pomegranate extract, including ellagitannins, anthocyanins, and phenols, have been shown to decrease the expression of cyclooxygenase-2 (COX-2) through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways [59,60]. This reduction leads to the lower production of pro-inflammatory prostaglandins and decreased cell proliferation. ...
... We have classified the major nutraceuticals found in pomegranate, and the structures of the identified compounds are illustrated in Figure 2. Additionally, we have classified the nutraceuticals present in pomegranate juice (Table 1) and seed ( Table 2) extracts [17,63,64]. The mechanisms of anti-inflammatory and anticancer effects of numerous compounds in pomegranate extract, including ellagitannins, anthocyanins, and phenols, have been shown to decrease the expression of cyclooxygenase-2 (COX-2) through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways [59,60]. This reduction leads to the lower production of pro-inflammatory prostaglandins and decreased cell proliferation. ...
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Pomegranate extract has potential benefits for women’s reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles. The extract’s rich nutrient profile supports placental development and fetal growth and may reduce the risk of preterm birth. Additionally, pomegranate extract shows promise in improving insulin sensitivity and reducing inflammation and oxidative damage in PCOS. Some studies suggest its potential anticancer properties, particularly against breast cancer. However, further research, including human clinical trials, is necessary to establish its effectiveness and safety. The current evidence is limited and primarily based on in vitro studies, animal studies, and clinical trials. This review provides a comprehensive summary of the benefits of pomegranate extract for women’s reproductive health and breast cancer, serving as a reference for future research.
... In Tunisia, the cultivation of pomegranate (Punica granatum L.) has become an important sector thanks to its benefits especially on the human health since it has a good antioxidant power and several vitamins. Infact, various disease risk factors, such as high blood pressure, high cholesterol, oxidative stress, hyperglycemia, and inflammatory activities, can be prevented or treated by using pomegranate [14]. However, this species is not suited to rain-fed cultivation and necessitates consistent access to water through regular irrigation. ...
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The role of pomegranate on folk medicine has been largely established and in recent years a notable increase of scientific support has occurred. However, what is real? Evidence suggests that phenolic phytochemicals of pomegranate fruit, mainly anthocyanins and ellagitannins, could exert multiple therapeutic properties on health management as playing an essential role in oxidative stress balance, preventing important cardiovascular diseases, and fighting as chemoprotective agent against several kinds of cancer. In addition, pomegranate antioxidant bioactives also could possess a role as neuroprotectors in some neurological disorders just as broad antimicrobial activities among other beneficial implications. Regarding promising prospects of pomegranate phenolics, this review summarizes the available scientific information related to health promotion features of pomegranate-derived products and underlines the influence of multiple constituents on the observed biological actions, pointing out pomegranate juice as interesting source to obtain the pomegranate attributed health benefits.
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