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Punica granatum

 

Punica granatum

Synonyms

No documentation

Vernacular Name

Pomegranate, POM, grenade, granada

Description

Punica granatum has an ancient history of use in each of the areas in which it grows. Not only is it used as a food and beverage source, and as a medicine, but it is carries religious importance in many cultures.

P. granatum is a small tree growing up to 8m tall and bearing fruit. It produces bright red flowers and produces a fruit, or berry, that is slightly smaller than a grapefruit. This fruit has a thick reddish-green skin and contains hundreds of seeds. The shiny, narrow leaves are approximately 6cm long and are opposite. This edible fruit has white to red pulp and is used as a food and for beverages.

Origin / Habitat

P. granatum is found in various parts of the world and is now cultivated in the Middle East, India and North American for its fruit and juice. It is thought to be native to the Himalayan area of India. It thrives in mildly temperate areas and can tolerate cool winters.

Chemical Constituents

Phenolic constituents include the polyphenols (ellagitannins, mainly punicalagin) and flavonoids (anthocyanins) and also the phenol ellagic acid; [2] beta sitosterol, ursolic acid, luteolin, quercetin, rutin, iron, kaempferol and amino acids. [3]

There are reports of P. granatum seed containing several steroidal hormones, including estrone and to a lesser extent estriol, 17-β-estradiol, and testosterone.[4] However, one study used definitive mass spectrometry and/or nuclear magnetic resonance analyses and could not confirm the presence of hormones in pomegranage. [5] They did find estrogen-binding constituents including luteolin, quercetin and kaempferol.

Plant Part Used

Juice, fruit, flower; seed oil, pericarp (peel and rind), leaves, roots and bark are also used indigenously.

Medicinal Uses

General

Antioxidant
Cardiovascular health, including blood pressure, cholesterol and oxidative stress
Cancer protective, including prostate
Diabetes – flower
Dental health
Antibacterial, topical
Anti-inflammatory

Most Frequently Reported Uses

Antioxidant
Cardiovascular health, including blood pressure, cholesterol and oxidative stress
Cancer protective, including prostate

Dosage

Dosage Range  

Encapsulated fruit: 250-500mg, 2 times daily of a standardized extract.

Most Common Dosage

Juice: 240mL (8 ounces) daily of unsweetened fruit juice.

Standardization Dosage 

Juice: Although not traditionally standardized, P. granatum juice polyphenolic components consist of approximately 80 -90% ellagitannins and gallotannins, 8-15% anthocyanins, and 2-5% ellagic acid. [1]

Pharmacology

Pre-clinical

P. granatum has high antioxidant potential, mainly due to polyphenolic constituents. [6],[7] P. granatum extracts have been reported to decrease free radical production, macrophage-induced oxidative stress and lipid peroxidation. An in vitro study found the P. granatum juice and seed extracts have 2-3 times the antioxidant capacity of either red wine or green tea. [8]

The laboratory studies have found that pretreatment of the skin with pomegranate-derived products inhibited UVB-induced damage to human skin, attributed to the high antioxidant potential. [9],[10]

The laboratory and clinical studies have found P. granatum juice consumption increases macrophage uptake of oxidized LDL, decreases lipid peroxidation, and decreases cholesterol levels. [11] The juice was also reported to activate peroxisome proliferator-activated receptor (PPAR-α), a cardiac transcription factor involved in myocardial energy production via fatty acid uptake and oxidation. [12]

The laboratory studies have reported that P. granatum juice has anticancer effects, including lung, breast, prostate, colon, leukemia, colon and skin cancer cell lines. [13] In vitro studies for prostate cancer have found that P. granatum decreases PSA levels,  inhibits prostate cancer cell growth, induces apoptosis of several prostate cancer cell lines (including highly aggressive PC-3 prostate carcinoma cells), suppress invasive potential of PC-3 cells, and decreases proliferation of DU-145 prostate cancer cells. [14],[15]

P. granatum seed oil has been reported in laboratory studies to inhibit both cyclooxygenase and lipoxygenase enzymes. [16] Another laboratory study found that P. granatum extract inhibited IL-1beta- induced destruction of proteoglycan, expression of matrix metalloproteinases (MMPs) at the cellular level, and phosphorylation and activation of mitogen-activated protein kinases (signal transduction molecules involved in MMP expression), potentially leading to prevention of collagen degradation and joint destruction in patients with osteoarthritis. [17]

The topical application of P. granatum extract has been reported to be effective against a variety of bacteria, including methicillin-resistant Staph. aurus (MRSA). [18] In a laboratory study, an extract of P. granatum increased the post-antibiotic effect of ampicillin from 3-7 hours, offering an alternative for the extension of the useful lifetime of these antibiotics. [19]

The antimicrobial activity of P. granatum has also been found to be useful in dental mouthwashes, by reducing total protein (correlating with reductions of plaque forming bacteria), reducing activities of aspartate aminotransferase (an indicator of cell injury), reducing alpha-glucosidase activity (a sucrose degrading enzyme), increasing activities of the antioxidant enzyme ceruloplasmin and increasing antioxidant activity in the oral cavity.[20] A laboratory study found that an oral preparation containing P. granatum extract decreased the number of colony forming units (CFU) of dental plaque bacteria by 84%, which was comparable to the pharmaceutical drug chlorhexidine (79% inhibition) and significantly better than the control rinse (11% inhibition). [21]

P. granatum extract was also found to decrease obesity-associated fatty liver in a laboratory animal study, at least in part, by activating hepatic expression of genes responsible for fatty acid oxidation. [22],[23]

Clinical

A human study that administered P. granatum juice to 30 patients with type 2 diabetes found that after 4 weeks, serum oxidative stress was significantly decreased by 35%, whereas serum concentrations of the antioxidant thiol groups significantly increased by 25%.[24] The authors also found that P. granatum juice consumption contributed to PON1 stabilization, increased association with HDL, and enhanced catalytic activities, potentially leading to a decline in atherosclerosis development in diabetic patients.

Both laboratory and human studies have reported P. granatum is effective in cardiovascular health, including atherosclerosis, antioxidant activity, myocardial perfusion, lipid levels and hypertension. [25] Five small human clinical trials testing cardiovascular activities have evaluated P. granatum juice for effects on cholesterol, atherosclerosis, myocardial perfusion, hypertension, and erectile dysfunction. A clinical study of 22 diabetic patients receiving concentrated P. granatum juice (40 grams daily for 8 weeks) found significant reductions in total cholesterol, low-density lipoprotein-cholesterol (LDL-c), LDL-c/high-density lipoprotein-cholesterol (HDL-c) ratio and total cholesterol/HDL-c ratios. [26]

A randomized, double-blind, parallel trial assessed in humans found that drinking P. granatum juice (240ml daily) may slow carotid intima-media thickness (CIMT) progression in individuals with increased oxidative stress and disturbances in the triglyceride-rich lipoprotein/HDL axis. [27] This may lead to a decreased risk for developing coronary heart disease.

P. granatum juice consumption in 10 hypertensive patients was found to inhibit serum angiotensin converting enzyme (ACE) by up to 36%, but only a 5% decrease in systolic blood pressure. [28] Another human study found that P. granatum juice consumption reduced myocardial ischemia and improved myocardial perfusion.

In an open-label, phase II clinical trial involving P. granatum juice (240ml) administration in 46 men with recurrent prostate cancer, 35% of the patients reported a significant decrease (av. 27%) in serum prostate specific antigen (PSA) levels during treatment. [29] In the same study, in vitro analysis found significant decreases in prostate cancer cell line proliferation and increased cancer cell apoptosis. The authors concluded that P. granatum juice consumption may affect prostate cancer because of antiproliferative, apoptotic, antioxidant, and potentially anti-inflammatory effects. Another laboratory study found P. granatum inhibits angiogenesis of breast cancer cells via downregulation of vascular endothelial growth factor.  [30] Other laboratory studies have found that P. granatum juice caused a significant decrease in COX-2 expression and inhibits NF-kappaB, leading to pomegranate’s anti-inflammatory and anticarcinogenic activity. [31],[32]

In a small human study, supplementation with ellagitannins from P. granatum extract significantly improved recovery of isometric strength following heavy exercise. [33]

The extracts of P. granatum flower have been reported in laboratory studies to have antidiabetic activity in laboratory studies, supporting traditional uses in individuals with diabetes. P. granatum flower was found to have dual PPAR-alpha/-gamma activator properties, improving glucose metabolism. [34] PAR-alpha is involved in the regulation of fatty acid (FA) uptake and oxidation, inflammation and vascular function, while PPAR-gamma participates in FA uptake and storage, glucose homeostasis and inflammation. As laboratory animal study found P. granatum extract improved postprandial hyperglycemia in rats with type 2 diabetes and obesity, at least in part, by inhibiting intestinal alpha-glucosidase activity. [35]

Encapsulated: Standardized to 40% ellagic acid and 40% punicosides 

Interaction and Depletions

Interaction with other Herbs

No documentation

Interaction with Drugs

P. granatum may alter cytochrome P450-3A hepatic enzyme system, which is responsible for the metabolism of many prescription drugs.

Based on pharmacology, use P. granatum supplements with caution in individuals taking anticonvulsant medications. One laboratory animal study found P. granatum juice increase the bioavailability of the anticonvulsant Carbamazepine (Tegretol). [38]

Based on pharmacology, use P. granatum supplements with caution in individuals taking hypoglycemic medications, such as tolbutamide (Tolinase). One laboratory animal study found P. granatum juice increase the bioavailability of the oral hypoglycemic tolbutamide (Tolinase). [39]

Based on pharmacology, use with caution in individuals taking blood-thinning medications such as aspirin or warfarin (Coumadin). P. granatum has been linked to alterations in warfarin metabolism and lead to an increased INR, according to one human case report. [40]

Precautions and Contraindications

Side effects

Discontinue if allergy occurs.

Pregnancy

P. granatum should be used with caution in pregnancy, as a laboratory study reports uterine stimulatory effects on rats. [36] However, a laboratory animal study found that maternal dietary supplementation of P. granatum was neuroprotective for the neonatal brain. [37]

Age limitation

No documentation

Adverse reaction

No documentation

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  1) Botanical Info

References 

  1. American Botanical Council. Scientific and Clinical Monograph for POM WONDERFUL® POMEGRANATE JUICE ©2008. Available from: www.herbalgram.org. [Accessed on 21 December 2009].
  2. Seeram NP, Henning SM, Zhang Y, et al. Pomegranate Juice Ellagitannin Metabolites Are Present in Human Plasma and Some Persist in Urine for Up to 48 Hours. Journal of Nutrition. 2006;136:2481-2485.
  3. Ahmed R, Ifzal SM, Saifuddin A, Nazeer M. Studies on Punica granatum. I. Isolation and identification of some constituents from the seeds of Punica granatum. Pakistan J Pharmaceut Sci. 1995;8:69–71.
  4. Moneam NMA, Sharaky AS, Badreldin MM. Estrogen content of pomagranate seeds. J Chromatogr. 1988;438:438–442.
  5. Van Elswijka D, Schobela U, Lansky E, et al. Rapid dereplication of estrogenic compounds in pomegranate (Punica granatum) using online biochemical detection coupled to mass spectrometry. Phytochem. 2004;65:233–241.
  6. Rosenblat M, Volkova N, Coleman R, Aviram M. Pomegranate byproduct administration to apolipoprotein e-deficient mice attenuates atherosclerosis development as a result of decreased macrophage oxidative stress and reduced cellular uptake of oxidized low-density lipoprotein. J Agric Food Chem. 2006;54:1928-1935.
  7. Guo C, Wei J, Yang J, Xu J, Pang W, Jiang Y. Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects. Nutr Res. Feb 2008;28(2):72-77.
  8. Gil MI, Tomas-Barberan FA, Hess-Pierce B, et al. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem. 2000;48:4581-4589.
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  11. Aviram M, Dornfeld L, Kaplan M, et al. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp Clin Res. 2002;28(2-3):49-62.
  12. Huang TH, Peng G, Kota BP, et al. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. Br J Pharmacol. 2005:145:767-774.
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  16. Shukla M, Gupta K, Rasheed Z, Khan KA, Haqqi TM. Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX2 activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro. J Inflamm (Lond). 13 Jun 2008;5:9.
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  18. Gould SW, Fielder MD, Kelly AF, Naughton DP. Anti-microbial activities of pomegranate rind extracts: enhancement by cupric sulphate against clinical isolates of S. aureus, MRSA and PVL positive CA-MSSA. BMC Complement Altern Med. 27 Jul 2009;9:23.
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  24. Rock W, Rosenblat M, Miller-Lotan R, Levy AP, Elias M, Aviram M. Consumption of wonderful variety pomegranate juice and extract by diabetic patient’s increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities. J Agric Food Chem. 24 Sep 2008;56(18):8704-8713.
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  38. Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome P450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos. 2005;33:644-648.
  39. Nagata M, Hidaka M, Sekiya H, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab Dispos. 2007;35(2):302-305.
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