Punica granata

Emily Menzen

Johnnie Shablack

April 28, 2008

The Pomegranate: who says it’s not wonderful?

Taxonomy [1]

Kingdom: Plantae Phylum: Tracheophyta Class: Magnoliopsida Order: Myrtales Family: Punicaceae Genus: Punica Species: granata (not granatum!)

http://forum.canucks.com/lofiversion/index.php/t184247.html

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 Each fruit contains numerous

seeds covered in fleshy arils (seed packets) contained in walls of membranous tissue

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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: Folkloreo 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

o During this time Demeter (Persephone’s mother) is sad and refuses to let the crops grow, thus the explanation for seasonality

http://www.pomegranatehealth.com/client_images/catalog19769/pages/images/persephone-small.jpg

Ancient Uses [4][5]

o Mentioned in the papyrus Ebers of Egypt in 1550BC

o Greek physicians advised women of childbearing age to ingest the seeds of pomegranate to prevent pregnancy

o 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

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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

Gastroenterological ailments and Ulcers Antiarthersceloris Prevent cancers Hypertension Diabetes

Rind and Bark of stem and roots 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 Acetone extracts of pomegranate are toxic to Pyricularia

oryzae and Colletotrichum falcatum Inhibits spore germination

Antiviral 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 4-8 grams

Flower Powder 4-5 grams

Root and Bark Powder 1.5-3 grams

Bark decoction 100-200 mL

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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 stress-induced 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]

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

In Vivo studies of Apolipoprotein E-deficient mice [14] [15]

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-MDA-231 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 CYP3A-

mediated 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 GC-mass 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: 286-294.

[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