Download Pomegranate

Punica granata
The Pomegranate: who says it’s not wonderful?
Emily Menzen
Johnnie Shablack
April 28, 2008
Taxonomy [1]








http://forum.canucks.com/lofiversion/index.php/t184247.html
Kingdom: Plantae
Phylum: Tracheophyta
Class: Magnoliopsida
Order: Myrtales
Family: Punicaceae
Genus: Punica
Species: granata
(not granatum!)
Botanical Description [2][3]




Short (less than 5 m), spiny
shrub with shiny leaves of 4-6
cm
Bears red/orange bell shaped
flowers
Deciduous
Produces red spherical fruits
approx 10 cm in diameter

http://www.pomwonderful.com/images/how2selectB.jpg
Each fruit contains numerous
seeds covered in fleshy arils
(seed packets) contained in
walls of membranous tissue
History [2][3][4]

Cultivated in: India,
Afghanistan,
Southeastern Europe
including the
Mediterranean, Egypt
and other parts of
Africa, Ancient Persia
(now the Modern
Middle East)

One of the oldest
herbals known in
traditional medicine,
used for thousands of
years in areas of the
Middle East and
Mediterranean
History: Folklore
o
o
http://www.pomegranatehealth.com/client_images/catalog19769/pages/
images/persephone-small.jpg
In ancient Greek mythology,
Persephone was tricked into
eating pomegranate seeds
which sentenced her to
spend 6 months of the year
underground married to
Hades
During this time Demeter
(Persephone’s mother) is
sad and refuses to let the
crops grow, thus the
explanation for seasonality
Ancient Uses [4][5]
o
o
o
Mentioned in the papyrus Ebers of Egypt
in 1550BC
Greek physicians advised women of
childbearing age to ingest the seeds of
pomegranate to prevent pregnancy
Giambattista della Porta suggested eating
the seeds to strengthen teeth back in 1588
with his book, Phytognomonica
A Traditional Use [2][4]


Pomegranates have
astringent properties
because of the alkaloids
(pelletierine tannate)
present in the bark of the
stems and roots and have
been used for many years
as an anthelmintic:
removing tapeworms
The chemicals cause the
tapeworm to loosen its hold
on the intestinal walls and
they can be removed from
the body through purging
www.stanford.edu
Traditional Uses Continued [3][4]





Is an ingredient in the medicine for the
treatment of various gastrointestinal
problems including dysentery and chronic
diarrhea
Used to treat postpartum symptoms
Rind is used to tan leather
Seed packets used in dyes
Grenadine was formerly made of
pomegranate juice and sugar
Modern Uses



Powerful Antioxidant
Has strong degree of free
radical scavenging, absorbs
oxygen radicals, lowers LDL
levels in blood
Shows in vitro anticancer
properties
www.pomwonderful.com/juice.html
Commercial Sources and Handling [2]

Fresh/Dried Pomegranates



Seeds, Pulps, Peels
Roots/bark/leaves for teas
Powder, pills, oil extracts,
and juices
http://www.pompills.com/img/home_new_bottle3.jpg
https://www.globalpackagegallery.com/main.php?g2_view=core.Do
http://www.dkimages.com/discover/previews/788/567138.JPG
http://figmagazine.com/winter06/whattoeatnow.html
Commercial Sources and Handling [3][6]

Collection/Processing




Ripe fruits harvested early fall (2-3”dia)
Roots, bark, leaves often dried
Powders formed by extraction of the fruit with
polar solvents and dried in hot air ovens
Storage



Fresh fruit kept up to a month in cool conditions
Seeds, bark, leaves can be kept in airtight bags,
frozen, or dried
Powders stored in dry conditions
http://www.danish-schnapps-recipes.com/images/pomegranate-tree-with-ripe-pomegranate-fruit-200.jpg
Commercial Sources and Handling [3][6]

Preparations




Fresh fruit pericarp and seeds eaten directly or
made into a juice
Decoctions of root bark, stem bark, leaves, and
young fruit
Infusions or tinctures of the fresh or dried fruit rind
Powders put in pill form or mixed with water
Commercial Sources and Handling [9][10]

Adulterants

Synthetic steroids have been a problem,
particularly in East Asia because of an interest in
phytoestrogens



Cause safety issues and can be life-threatening
GC methods have been used to screen for steroids in
preparations
Ellagic acid added to extracts

Used to meet the final extract amount without spending
the money on more material
Medicinal Properties and Uses [2][7][8]

Juice of Leaves and Fruits






Rind and Bark of stem and roots




Gastroenterological ailments and Ulcers
Antiarthersceloris
Prevent cancers
Hypertension
Diabetes
Anthelmintic
Antidiarrheal
Promotes mucous discharge
Dried Flowers

Hematuria, hemorrhoids, hemoptysis, dysentery, chronic
diarrhea, and bronchitis
Constituents [2][3][13]

Fruit Rind and Pulp

Antioxidants





Polyphenols
Tannins (Ellagitannins)
Anthocyanins
Steroid estrogen estrone (one of the few plants in nature)
Roots, Bark, Leaves, Young Fruit

Piperidine alkaloids



Pelletierine, Isopelletierine (Active)
N-methylisopelletierine, pseudopelletierine (Inactive)
Punico tannic acid
Chromatogram [12]

Tannins and Punicalagins highest
constituents (C and D)
Left: Fresh juice extract from arils; and Right: juice from whole pomegranates
Types of Activity [3][11][13]

Tannins and Polyphenols



Ellagitannins seen to inhibit cancer cell proliferation by
suppressing specific proteins
Antidiarrheal effect
Antiatherosclerotic


Inhibits low-density lipoprotein oxidation
Piperidine Alkaloids


Astringent
Anthelminic

Interact with nicotinic acetylcholine receptors and narcotise
tapeworms
Types of Activity [2][8]

Fungitoxic



Antiviral



Acetone extracts of pomegranate are toxic to Pyricularia
oryzae and Colletotrichum falcatum
Inhibits spore germination
Blocks the binding of HIV-1 to the receptors CD4 and
CXCR4/CCR5
Inhibit infection by primary virus clades A to G and group O
Antimicrobial


Enhanced effects of antibiotics (syngeric interaction)
Inhibits the growth of Staphylococcus aureus
Dosages [2]

Fruit Powder


Flower Powder


4-5 grams
Root and Bark Powder


4-8 grams
1.5-3 grams
Bark decoction

100-200 mL
http://www.ishopindian.com/shop/files/proddetailimages/d_620.gif
Which is best? [20]


Study compared multiple antioxidant properties
of pomegranate juice in comparison to other
beverages sold in the US
Results showed that “Antioxidant potency, ability
to inhibit LDL oxidation, and total polyphenol
content were consistent in classifying the
antioxidant capacity of the polyphenol-rich
beverages in the following order: PJ > red wine >
Concord grape juice > blueberry juice > black
cherry juice, açaí juice, cranberry juice > orange
juice, iced tea beverages, apple juice.” plus PJ
had a 20% higher antioxidant index than the rest
Pharmacodynamics [16]


In vitro experiments show that pomegranate
juice interferes with cytochrome P450 just like
grapefruit juice, increasing the concentration of
Carbamazapine (an anticonvulsant and bipolar
medication) by inhibiting CYP3A enzymes in
liver cells irreversibly
Also the study demonstrated that pomegranate
juice influenced the pharmacokinetics of
carbamazepine in rats
Pharmacodynamics [18]


Another study involving in vitro and in
human subjects indicated that
pomegranate juice (PJ) does not interfere
with cytochrome P450 activity like
grapefruit juice (GFJ)
PJ did not elevate levels of Midazolam
(benzodiazepine derivative) in the blood,
or alter the elimination half-life, volume of
distribution, or clearance of drug whereas
GFJ has this effect
Pharmacokinetics of Ellagic Acid (EA)
[17]


In an experiment testing the bioavailability of
Ellagic Acid (a potent anti-oxidant and anti-tumor
compound) in rat blood from pomegranate leaf
extracts through oral administration shows that it
is absorbed quickly (mostly through the stomach)
and is distributed rapidly, however it peaks and
dissipates too fast for the tissues to absorb
enough of the potential benefits of the compound
Peak concentrations in plasma were 203 µg/ml in
0.54 h and half life was 0.77 h
Plasma Concentration of EA [17]
Plasma concentration–time curve of EA in rats after oral administration of
pomegranate leaf extract (at a dose containing 85.3 μg/kg EA). Each point and
bar represents the mean±S.D. (n=5).
Therapeutic Activity [14]




Anti-oxidant
Helps diabetics with oxidation of lipids and
moderately lowered their serum cholesterol levels
(without affecting blood sugar)
Aids coronary artery disease patients with stressinduced myocardial ischemia (angina)
Helps carotid artery stenosis patients by reducing
the size of their atherosclerotic lesions
Clinical Studies [21]


A phase II study on men with prostate
cancer who drank 8 oz of POM wonderful
a day until disease progression showed a
decrease in mean PSA (prostate-specific
antigen) doubling time from 15 months
baseline to 54 post treatment
In vitro studies showed a 12% decrease in
cell proliferation and a 17% increase in
apoptosis
“Herbal Synergy” [22]



Dr. Ephraim Lanksy researched the effect of
all phytochemical compounds at once in the
treatment of cancer using in vitro studies
Discovered the anticancer effect was greater
when all components work together
Discovered that “the mode of inhibition is
varied, including programmed cell death,
invasion inhibition, proliferation inhibition, and
angiogenesis”
Phenolics are Anti-atherogenic [14]



Used as anti-atherogenesis medicine.
 Atherogenesis is when there is a build up of lipids that
contain plaques in the internal arteries of the body
Oxidation of LDL causes an increase in cellular uptake of
“bad” lipids
“Pomegranate juice (PJ)…contains several unique
polyphenolics and sugars. Pomegranate soluble
polyphenols contain hydrolyzable tannins such as the
ellagitannin punicalagin, gallic and ellagic acids, as
well as anthocyanins and catechins. Consumption of PJ
by healthy subjects for as little as 2 weeks, significantly
reduced the oxidation of LDL…”
Polyphenols Present [14]
In Vivo studies of Apolipoprotein E-deficient
mice [14] [15]


•
Oxidation of LDL causes an increase in
cellular uptake of “bad” lipids and leads to
atherogenesis
Apolipoprotein E binds to very low density
lipids and carries them to the liver to be
processed
Analyzed the properties in the peels, arils, seeds
and flowers of the plant compared to the fruit juice

Wanted to see the individual effects of each part
Pomegranate extracts reduce atherosclerotic lesion
size [14]
Figure 2. Effects of pomegranate extracts consumption by E0 mice on their atherosclerotic lesion size.
Apolipoprotein E-deficient mice (E0 mice) consumed PJ, POMxl, POMxp, POMa, or POMf (200 μg of
GAE/mouse/day) for 3 months. The placebo mice received only water. The atherosclerotic lesion area was
significantly decreased by 44, 38, 39, or by as much as 70%, respectively, as compared to lesion area observed
in the placebo-treated group
Results of In Vivo [14]
In Vitro Anticancer Studies [19]


“Polyphenols from fermented juice at concentration ranging
from100 to 1000 mg/ml inhibited aromatase activity by 60–
80% and 17-b-hydroxysteroid dehydrogenase Type 1 activity
by 79%. In two breast cancer cell lines MCF-7 and MB-MDA231 cells, fermented pomegranate juice polyphenols
consistently showed about twice the anti-proliferative effect
as fresh pomegranate juice polyphenols.”
“pomegranate fruit extract (PFE) possesses remarkable
antiproliferative and pro-apoptotic properties against human
PCa cells both in vitro and in vivo. Treatment of human PCa
PC-3 cells with an extract of pomegranate fruit (PFE, 10–100
mg/ml; 48 h) resulted in a dose-dependent inhibition of cell
growth/cell viability and induction of apoptosis.”
Contraindications [23]

Pregnant/nursing women should avoid
overuse



May cause cramps, vomiting, and diarrhea
Should not be taken with oil or fats when
used to treat parasite infections.
People who are allergic to Pomegranate are
also allergic to other fruits, pollen or nuts.
Adverse Effects and Interactions [16][7]

May inhibit cytochrome P450 3A-mediated
drugs





Components of pomegranate interact with CYP3Amediated metabolism of carbamazepines
(anticonvulsants and mood stabilizers)
BUT, studies are still unclear
High amounts of tannins can be toxic, but rare
Dried rinds may contain aflatoxin B-1
May cause bronchospasms due to the
astringent properties of the alkaloids
References
[1] Punica granatum “Garnet Sash”. March 14, 2008. < www.zipcodezoo.com > 04/24/08
[2] Kapoor, L.D. 2001. Ayurvedic Medicinal Plants. Boca Raton: CRC Press. 280-281.
[3] Van Wyk, B.E. and M. Wink. 2004. Medicinal Plants of the World. Portland: Timber Press. 263,
374, 424.
[4] Iwu Maurice M. Handbook of African Medicinal Plants. Boca Raton: CRC Press. 224-225.
[5] Sumner Judith. The Natural History of Medicinal Plants. Portland: Timber Press. 21, 31.
[6] Kulkarni, A.P, S.M. Aradhya, and S. Divakar. 2004. “Isolation and Identification of radical
scavenging antioxidant – punicalagin from pith and carpellary membrane of pomegranate fruit.”
Food Chemistry. 87(4):551-557
[7] Langley, P. 2000. “Why a Pomegranate?” British Medical Journal. 321(7269): 1153-1154.
[8] Louba, B.N. 2007. “What are the medical properties of pomegranates?” Journal of Chinese Clinical
Medicine. 2(9).
[9] Choi, D.W., J.Y. Kim, S.H. Choi, H.S. Jung, H.J. Kim, S.Y. Cho, C.S. Kang, and S.Y. Chang. 2006.
“Identification of S=steroid hormones in pomegranate (Punica granatum) using HPLC and GCmass spectrometry.” Food Chemistry. 96(4): 562-571.
[10] Meyers, S. 2007. “The Complexities of Botanical Quality.” Natural Products Insider. 24. Sep. 2007.
[11] Sumner, M.D., M. Elliot-Eller, G. Weidner, J. Daubenmier, M. Chew, R. Marlin, C. Raisin, and D.
Ornish. 2005. “Effects of Pomegranate Juice Consumption on Myocardial Perfusion in Patients
with Coronary Heart Disease.” The American Journal of Cardiology. 96(6): 810-814.
References
[12] Gil, M.I., F.R. Barberan, B. Hess-Pierce, D.M. Holcroft, A.A Kader. 2000. “Antioxidant activity of
Pomegranate Juice and Its Relationship with Phenolic Composition and Processing.” J. Agric. Food
Chem. 48(10): 4581-4589.
[13] Adams, L.S., N.P. Seeram, B.B. Aggarwal, Y. Takada, D. Sand, and D. Heber. 2006. “Pomegranate
juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in
colon cancer cells.” J Agric Food Chem. 54(3): 980-5.
[14] Pomegranate Phenolics from the Peels, Arils, and Flowers Are Antiatherogenic: Studies in Vivo in
Atherosclerotic Apolipoprotein E-Deficient (E0) Mice and in Vitro in Cultured Macrophages and
Lipoproteins
[15] Definition of Apolipoprotein E. September 3, 2004. < http://www.medterms.com > 04/25/08
[16] Hidaka, M., M. Okumura, K. Fujita, T. Ogikubo, K. Yamasaki, T Iwakiri, N Setoguchi, and K
Arimori. 2005. “Effects of pomegranate juice on human cytochrome P450 3A (CYP3A) and
carbamazepine pharmacokinetics in rats. Drug Metab Dispos. 33(5): 644-8.
[17] Lei, F., D.M. Xing, L. Xiang, Y.N. Zhao, W. Wang, L.J. Zhang, L.J. Du. 2003. “Pharmacokinetic
study of ellagic acid in rat after oral administration of pomegranate leaf extract.” Jour of
Chromatography B. 796(1): 189-194
[18] Farkas, D., L.E. Oleson, Y. Zhao, J.S. Harmatz, M. Zinny, M. Court, and D.J. Greenblatt. 2007.
“Pomegranate Juice Does Not Impair Clearance of Oral or Intravenous Midazolam, a Probe for
Cytochrome P450-3A Activity: Comparison With Grapefruit Juice.” J Clin Pharmacol. 47: 286294.
[19] Adhami, V.Q., and H. Mukhtar. 2006. “Polyphenols from green tea and pomegranate for
prevention of prostate cancer.” Free Radical Research. 40(10): 1095-1104
References
[20] Seeram, N.P., M. Aviram, Y. Zhang, S. Henning, L. Feng, M. Dreher, and D. Heber. 2008.
“Comparison of Antioxidant Potency of Commonly Consumed Polyphenol-Rich Beverages in
the United States” Journ of Agri and Food Sci. 56(4): 1415-1422.
[21] Pantuck, A.J., J.T. Leppert, N. Zomorodian, W. Aronson, J. Hong, R.J. Barnard, N. Seeram, H.
Liker, H. Wang, R. Elashoff, D. Heber, M. Aviram, L. Ignarro, and A. Belldegrun. 2006. “Phase
II Study of Pomegranate Juice for Men with Rising Prostate-Specific Antigen following Surgery
or Radiation for Prostate Cancer” Clinical Cancer Research. 12: 4018-4026
[22] Robert Longtin. 2003. The Pomegranate: Nature’s Power Fruit? Journal of the National Cancer
Institute, 95(5): 346-348
[23] Loren, D.J. 2005 “Maternal Dietary Supplementation with Pomegranate Juice is
Neuroprotective in an Animal Model of Neonatal Hypoxic-Ischemic Brain Injury.” Pediatric
Research. 57(6): 858-864