Punica granata Emily Menzen

Punica granata

• Emily Menzen

• Johnnie Shablack

• April 28, 2008

Kingdom: Plantae

• Kingdom: Plantae

• Phylum: Tracheophyta

• Class: Magnoliopsida

• Order: Myrtales

• Family: Punicaceae

• Genus: Punica

• Species: granata

• (not granatum!)

Short (less than 5 m), spiny shrub with shiny leaves of 4-6 cm

• 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

Cultivated in: India, Afghanistan, Southeastern Europe including the Mediterranean, Egypt and other parts of Africa, Ancient Persia (now the Modern Middle East)

• Cultivated in: India, Afghanistan, Southeastern Europe including the Mediterranean, Egypt and other parts of Africa, Ancient Persia (now the Modern Middle East)

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

• 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

Mentioned in the papyrus Ebers of Egypt in 1550BC

• 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

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

• 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

Is an ingredient in the medicine for the treatment of various gastrointestinal problems including dysentery and chronic diarrhea

• 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

Powerful Antioxidant

• Powerful Antioxidant

• Has strong degree of free radical scavenging, absorbs oxygen radicals, lowers LDL levels in blood

• Shows in vitro anticancer properties

Commercial Sources and Handling [2]

• Fresh/Dried Pomegranates

• Seeds, Pulps, Peels

• Roots/bark/leaves for teas

• Powder, pills, oil extracts, and juices

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

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

Study compared multiple antioxidant properties of pomegranate juice in comparison to other beverages sold in the US

• 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

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

• 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

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)

• 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

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

• 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

Anti-oxidant

• 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

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

• 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

Dr. Ephraim Lanksy researched the effect of all phytochemical compounds at once in the treatment of cancer using in vitro studies

• 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”

Used as anti-atherogenesis medicine.

• 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…”

Oxidation of LDL causes an increase in cellular uptake of “bad” lipids and leads to atherogenesis

• 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

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

• 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

“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.”

• “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

[1] Punica granatum “Garnet Sash”. March 14, 2008. < www.zipcodezoo.com > 04/24/08

• [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