Punica granatum L.

Last updated: 4 Nov 2016

Scientific Name

Punica granatum L.

Synonyms

Punica florida Salisb. [Illegitimate], Punica grandiflora Steud. [Invalid], Punica nana L., Punica spinosa Lam. [Illegitimate], Rhoea punica St.-Lag. [Illegitimate]. [1]

Vernacular Name

Malaysia Delima [2]
English Pomegranate [2]
China An shih liu, shan shih liu, shi liu, shi liu pi [2]
India Aab-e-amar, ama, amardana, anar, anara, anar-dakum, anar dana, anar-ka-per, atalai, cukavallam, cukkilestam, daadimba, daalimb, dadima-chetu, dadimba, dalika, dalimgachh, darakhte-gulnar, dhalim, ekamuli, hulidalimbe, irattavicam, jaram naro, kalumal madalai, kavaiyal, lohitapuspaka, madalum vayr, madhulami, magilam palam, matalam, milapatraka, nagarata, naspal, palapurakamaram, pulimadalai, rub anar, shukavallabha, tantapijakam, urumampalam, vrittaphala [2]
Indonesia Delima [2]
Thailand Ma-ko, ma koh, maak chang, phi laa, philaa khaao, siae lin, thap-thim, tubtim [2]
Vietnam An thach luu, mac liu [2]; lu’u, thap lu’u [3]
Cambodia Totum [3]
Laos Ph’iilaa [3]
Philippines Granada [2]
Nepal Anar [2]
Tibet Bal-poi-seu, se-‘bru, sen dju, se bru, seu bru [2]
Japan Hime-zakuro (for the dwarf variety), zakuro [2]
East Africa Nkomawawanga [2]
Nigeria Rimani, rummani [2]
Pakistan Anar [2]
Saudi Arabia Roman, rommen, ruman [2]
France Grenadier [3]
South America Granada, granadilla, granado, yaga tini, yanuko, xoba zehe, zehe castilla [2].

Geographical Distributions

Punica granatum is native to Asia particularly to Iran, Afghanistan and the Himalayas. From there, it was introduced and naturalised in the Mediterranean region, where it has been cultivated since ancient times. Now, it is grown throughout the tropics and subtropics. [3]

Botanical Description

P. granatum is a member of the family Punica. It is a deciduous shrub or small crooked tree that can grow up to 6(-10) m tall. It is often much branched near the base. The branches are often ending in a spine but also with axillary spines, and sometimes leaf-bearing themselves. [3]

The leaves are mostly arranged opposite but sometimes subopposite or clustered, oblong-lance-shaped, with acute or obtuse base, entire margin, obtuse or emarginated apex, shiny above and firmly herbaceous with prominent midrib beneath. The petiole is very short. [3]

The flowers are at the top of the twigs, waxy and measure 4-5 cm long and wide. The sepal and receptacle are 2-3 cm high, red or pale-yellow, fleshy and acutely 5-8-lobed. There are 3-7 petals which are crinkled, red, white or variegated. The stamens are numerous and the style surpasses the stamens. [3]

The fruit is a spherical berry, measures 6-12 cm in diametre, crowned by a persistent sepal, very variable in colour from yellow-green to black-violet and with leathery skin. The interior of the fruit is separated by membranous walls and white spongy tissue into compartments that are packed with transparent sacs and each filled with juicy pulp and a seed. [3]

The seeds are obtuse-angular, red, pink or yellow-white. [3]

Cultivation

P. granatum is a hardy subtropical species and surviving low winter temperatures (-10°C). The best quality fruits are produced in areas with cool winters and hot, dry summers; it does not fruit well in very humid climates. Under dry conditions, irrigation is needed to sustain high yield levels. The tree can tolerate soils on which most fruit crops do not thrive including calcareous and alkaline soils. In Southeast Asia, the tree grows well up to 1600 m elevation on a wide range of soil types; in wetter regions, the tree becomes evergreen, flowering and fruiting become protracted and fruit quality is inferior. [3]

Chemical Constituent

P. granatum has been reported to contain phenolic constituents and polyphenols (e.g. ellagitannins and punicalagin) and flavonoids (e.g. anthocyanins) and also the phenol ellagic acid [4], β-sitosterol, ursolic acid, luteolin, quercetin, rutin, iron, kaempferol and amino acids [5].

There are reports of P. granatum seed containing several steroidal hormones, including estrone and to a lesser extent estriol, 17-β-estradiol, and testosterone [6]. However, one study used definitive mass spectrometry and/or nuclear magnetic resonance analyses and could not confirm the presence of hormones in P. granatum. They did find estrogen-binding constituents including luteolin, quercetin and kaempferol [7].

Plant Part Used

Bark, fruit, roots. [3]

Traditional Use

The fruit is eaten fresh or the juice is extracted to prepare a refreshing, thirst-allaying drink ('grenadine'). In Asia the juice is also thickened to syrup which is used as a sauce. The fruit is an old symbol of prosperity and fertility; in the form of 'rujak', a traditional fruit salad, it plays a prominent role in the pregnancy ceremony in Java and other parts of Indonesia. However, fruit yield and quality tend to be poor in South-East Asia and the tree- almost every part of the plant is more often used for medicinal purposes; pomegranate figures in many oriental accounts of materia medica. Gargles are prepared from the dry rind of the fruit and fruit juice is given to persons suffering from fever. In Asia the bark of the branches and roots is a well-known remedy against tapeworms and other intestinal worms. The astringent properties of bark, leaves, immature fruit and fruit rind are used in decoctions against diarrhoea and dysentery. The astringency is due to the presence of tannins; the bark, leaves and fruit rinds are in fact good sources of tannin. [3]

Preclinical Data

Pharmacology

Antioxidant activity

P. granatum has high antioxidant potential, mainly due to polyphenolic constituents [8][9]. 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 [10].

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. [11][12]

Cholesterol regulatory activity

The laboratory and clinical studies have found P. granatum juice consumption increases macrophage uptake of oxidized LDL, decreases lipid peroxidation, and decreases cholesterol levels [13]. 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. [14]

Anticancer activity

The laboratory studies have reported that P. granatum juice has anticancer effects, including lung, breast, prostate, colon, leukemia, colon and skin cancer cell lines [15]. 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. [16][17]

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]

Antimicrobial activity

The topical application of P. granatum extract has been reported to be effective against a variety of bacteria, including methicillin-resistant Staphaurus (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]

Toxicity

No documentation

Clinical Data

Clinical findings

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%. 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. [24]

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 g 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 (240 mL daily) may slow carotid intima-media thickness (CIMT) progression in individuals with increased oxidative stress and disturbances in the triglyceride-rich lipoprotein/HDL axis. This may lead to a decreased risk for developing coronary heart disease. [27]

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. Another human study found that P. granatum juice consumption reduced myocardial ischemia and improved myocardial perfusion. [28]

In an open-label, phase II clinical trial involving P. granatum juice (240 mL) 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 its 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].

Precautions

No documentation

Side effects

No documentation

Pregnancy/Breast Feeding

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

Interaction & Depletion

Interaction with drug

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]

Interaction with other Herbs

No documentation

Contraindications

No documentation

Case Report

No documentation

Dosage

No documentation

Poisonous Management

No documentation

Line drawing

230

Figure Figure 1: The line drawing of P. granatum [3]

References

  1. The Plant List. Ver 1.1. Punica granatum L. [homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2016 Oct 24]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-2536844
  2. Quattrocchi U. CRC World dictionary of plant names: Common names, scientific names, eponyms, synonyms, and etymology. Volume III M-Q. Boca Raton, Florida: CRC Press, 2000; p. 782-783.
  3. Sudiarto, Rifai MA. Punica granatum L. In: Verheij EWM, Coronel RE, editors. Plant Resources of South-East Asia No. 2: Edible fruits and nuts. Wageningen, Netherlands: Pudoc, 1991; p. 270-272.
  4. 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. J Nutr. 2006;136(10):2481-2485.
  5. 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. Pak J Pharm Sci. 1995;8(1):69-71.
  6. Moneam NMA, Sharaky AS, Badreldin MM. Estrogen content of pomagranate seeds. J Chromatogr. 1988;438:438-442.
  7. 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(2):233–241.
  8. 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(5):1928-1935.
  9. 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. 2008;28(2):72-77.
  10. 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(10):4581-4589.
  11. Afaq F, Zaid MA, Khan N, Dreher M, Mukhtar H. Protective effect of pomegranate-derived products on UVB-mediated damage in human reconstituted skin. Exp Dermatol. 2009;18(6):553-561.
  12. Pacheco-Palencia LA, Noratto G, Hingorani L, Talcott ST, Mertens-Talcott SU. Protective effects of standardized pomegranate (Punica granatum L.) polyphenolic extract in ultraviolet-irradiated human skin fibroblasts. J Agric Food Chem. 2008;56(18):8434-8441.
  13. 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.
  14. 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.
  15. Khan SA. The role of pomegranate (Punica granatum L.) in colon cancer. Pak J Pharm Sci. Jul 2009;22(3):346-348.
  16. Malik A, Mukhtar H. Prostate cancer prevention through pomegranate fruit. Cell Cycle. 2006;5:371-373.
  17. Malik A, Afaq F, Sarfaraz S, et al. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci USA. 2005;102:14813-14818.
  18. 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). 2008 Jun 13;5:9.
  19. Ahmed S, Wang N, Hafeez BB, Cheruvu VK, Haqqi TM. Punica granatum L. extract inhibits IL-1beta-induced expression of matrix metalloproteinases by inhibiting the activation of MAP kinases and NF-kappaB in human chondrocytes in vitro. J Nutr. 2005;135(9):2096-2102.
  20. DiSilvestro RA, DiSilvestro DJ, DiSilvestro DJ. Pomegranate extract mouth rinsing effects on saliva measures relevant to gingivitis risk. Phytother Res. 2009;23(8):1123-1127.
  21. Menezes SM, Cordeiro LN, Viana GS. Punica granatum (pomegranate) extract is active against dental plaque. J Herb Pharmacother. 2006;6(2):79-92.
  22. Xu KZ, Zhu C, Kim MS, Yamahara J, Li Y. Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity. J Ethnopharmacol. 2009;123(2):280-287.
  23. Bagri P, Ali M, Aeri V, Bhowmik M, Sultana S. Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Food Chem Toxicol. 2009;47(1):50-54.
  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. 2008;56(18):8704-8713.
  25. Basu A, Penugonda K. Basu A, Penugonda K. Pomegranate juice: A heart-healthy fruit juice. Nutr Rev. 2009;67(1):49-56.
  26. Esmaillzadeh A, Tahbaz F, Gaieni I, et al. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam Nutr Res. 2006;76(3):147-151.
  27. Davidson MH, Maki KC, Dicklin MR, et al. Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease. Am J Cardiol. 2009;104(7):936-942.
  28. Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis. 2001;158(1):195-198.
  29. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006;12(3):4018-4026.
  30. Khan GN, Gorin MA, Rosenthal D, et al. Pomegranate fruit extract impairs invasion and motility in human breast cancer. Integr Cancer Ther. 2009;8(3):242-253.
  31. Adams LS, Seeram NP, Aggarwal BB, et al. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem. 2006;54(3):980-985.
  32. Rettig MB, Heber D, An J, Seeram NP, et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther. 2008;7(9):2662-71. Erratum in: Mol Cancer Ther. 2008;7(11):3654.
  33. Trombold JR, Barnes JN, Critchley L, Coyle EF. Ellagitannin Consumption improves strength recovery 2-3 days after eccentric exercise. Med Sci Sports Exerc. 2010;42(3):493-498.
  34. Li Y, Qi Y, Huang TH, Yamahara J, Roufogalis BD. Pomegranate flower: A unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties. Diabetes Obes Metab. 2008;10(1):10-17.
  35. Li Y, Wen S, Kota BP, Peng G, Li GQ, Yamahara J, Roufogalis BD. Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats. J Ethnopharmacol. 2005;99(2):239-244.
  36. Promprom W, Kupittayanant P, Indrapichate K, Wray S, Kupittayanant S. The effect of pomegranate seed extract and beta-sitosterol on rat uterine contractions. Reprod Sci. 2010;17(3):288-296.
  37. Loren DJ, Seeram NP, Schulman RN, Holtzman DM. Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. Pediatr Res. 2005;57(6):858-864.
  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(5):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.
  40. Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy. 2009;(8):1002-1006.