Advanced Biomedical Research

Potent health effects of pomegranate

Authors

1 Physiology Research Center, Isfahan Cardiovascular Research Institute, Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Accumulating data clearly claimed that Punica granatum L. (pomegranate) has several health benefits. Pomegranates can help prevent or treat various disease risk factors including high blood pressure, high cholesterol, oxidative stress, hyperglycemia, and inflammatory activities. It is demonstrated that certain components of pomegranate such as polyphenols have potential antioxidant, anti-inflammatory, and anticarcinogenic effects. The antioxidant potential of pomegranate juice is more than that of red wine and green tea, which is induced through ellagitannins and hydrosable tannins. Pomegranate juice can reduce macrophage oxidative stress, free radicals, and lipid peroxidation. Moreover, pomegranate fruit extract prevents cell growth and induces apoptosis, which can lead to its anticarcinogenic effects. In addition, promoter inhibition of some inflammatory markers and their production are blocked via ellagitannins. In this article, we highlight different studies on the therapeutic effects of pomegranate and their suggested mechanisms of actions.

Keywords

1. Ercisli S, Gadze J, Agar G, Yildirim N, Hizarci Y. Genetic relationships among wild pomegranate (Punica granatum) genotypes from Coruh Valley in Turkey. Genet Mol Res 2011;10:459-64.  Back to cited text no. 1
    
2. Newman R. A wealth of phtochemicals. Pomegranate: The Most Medicinal Fruit (Large Print 16pt). Sydney, Australia: Readhowyouwant; 2011. p. 184.  Back to cited text no. 2
    
3. Newman RA, Lansky EP, Block ML.-A Wealth of Phytochemicals. Pomegranate: The Most Medicinal Fruit. Laguna Beach, California: Basic Health Publications; 2007. p. 120.  Back to cited text no. 3
    
4. USDA 2010. Pomegranates, Raw. United States Department of Agriculture. http://www.nal.usda.gov. [Accessed September 2010].Jurenka JS. Therapeutic applications of pomegranate (Punica granatum L.): A review. Altern Med Rev 2008;13:128-44.  Back to cited text no. 4
    
5. Malik A, Afaq F, Sarfaraz S, Adhami VM, Syed DN, Mukhtar H. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc Natl Acad Sci U S A 2005;102:14813-8.  Back to cited text no. 5
    
6. Rettig MB, Heber D, An J, Seeram NP, Rao JY, Liu H, et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-kappaB-dependent mechanism. Mol Cancer Ther 2008;7:2662-71.  Back to cited text no. 6
    
7. Albrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel A, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food 2004;7:274-83.  Back to cited text no. 7
    
8. Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat 2002;71:203-17.  Back to cited text no. 8
    
9. Mehta R, Lansky EP. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev 2004;13:345-8.  Back to cited text no. 9
    
10. Khan N, Hadi N, Afaq F, Syed DN, Kweon MH, Mukhtar H. Pomegranate fruit extract inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice. Carcinogenesis 2007;28:163-73.  Back to cited text no. 10
    
11. Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agric Food Chem 2006;54:980-5.  Back to cited text no. 11
    
12. Hora JJ, Maydew ER, Lansky EP, Dwivedi C. Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice. J Med Food 2003;6:157-61.  Back to cited text no. 12
    
13. Syed DN, Malik A, Hadi N, Sarfaraz S, Afaq F, Mukhtar H. Photochemopreventive effect of pomegranate fruit extract on UVA-mediated activation of cellular pathways in normal human epidermal keratinocytes. Photochem Photobiol 2006;82:398-405.  Back to cited text no. 13
    
14. 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;56:8434-41.  Back to cited text no. 14
    
15. Gil MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000;48:4581-9.  Back to cited text no. 15
    
16. Stowe CB. The effects of pomegranate juice consumption on blood pressure and cardiovascular health. Complement Ther Clin Pract 2011;17: 113-5.  Back to cited text no. 16
    
17. Mohan M, Waghulde H, Kasture S. Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic Wistar rats. Phytother Res 2010;24:S196-203  Back to cited text no. 17
    
18. Aviram M, Rosenblat M, Gaitini D, Nitecki S, Hoffman A, Dornfeld L, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr 2004;23:423-33.  Back to cited text no. 18
    
19. Mirmiran P, Fazeli MR, Asghari G, Shafiee A, Azizi F. Effect of pomegranate seed oil on hyperlipidaemic subjects: A double-blind placebo-controlled clinical trial. Br J Nutr 2010;104:402-6.  Back to cited text no. 19
    
20. Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: Studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr 2000;71:1062-76.  Back to cited text no. 20
    
21. Kaplan M, Hayek T, Raz A, Coleman R, Dornfeld L, Vaya J, et al. Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr 2001;131:2082-9.  Back to cited text no. 21
    
22. de Nigris F, Williams-Ignarro S, Sica V, Lerman LO, D'Armiento FP, Byrns RE, et al. Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. Cardiovasc Res 2007;73:414-23.  Back to cited text no. 22
    
23. Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam Nutr Res 2006;76:147-51.  Back to cited text no. 23
    
24. 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;47:50-4.  Back to cited text no. 24
    
25. Huang TH, Yang Q, Harada M, Li GQ, Yamahara J, Roufogalis BD, et al. Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: Modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. J Cardiovasc Pharmacol 2005;46:856-62.  Back to cited text no. 25
    
26. Huang TH, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, et al. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: Role of lowering circulating lipids. Br J Pharmacol 2005;145:767-74.  Back to cited text no. 26
    
27. Hontecillas R, O'Shea M, Einerhand A, Diguardo M, Bassaganya-Riera J. Activation of PPAR gamma and alpha by punicic acid ameliorates glucose tolerance and suppresses obesity-related inflammation. J Am Coll Nutr 2009;28:184-95.  Back to cited text no. 27
    
28. Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, DU LJ. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 2007;31:1023-9.  Back to cited text no. 28
    
29. Vroegrijk, IO, van Diepen JA, van den Berg S, Westbroek I, Keizer H, Gambelli L. Pomegranate Seed Oil, a rich source of Punicic Acid, prevents diet-induced obesity and insulin resistance in mice. Food Chem Toxicol 2011;49:1426-30.  Back to cited text no. 29
    
30. 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;123:280-7.  Back to cited text no. 30
    
31. de Nigris F, Balestrieri ML, Williams-Ignarro S, D'Armiento FP, Fiorito C, Ignarro LJ, et al. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide 2007;17:50-4.  Back to cited text no. 31
    
32. Kahya V, Meric A, Yazici M, Yuksel M, Midi A, Gedikli O. Antioxidant effect of pomegranate extract in reducing acute inflammation due to myringotomy. J Laryngol Otol 2011;1:370-5.  Back to cited text no. 32
    
33. González-Sarrías A, Larrosa M, Tomás-Barberán FA, Dolara P, Espín JC. NF-kappaB-dependent anti-inflammatory activity of urolithins, gut microbiota ellagic acid-derived metabolites, in human colonic fibroblasts. Br J Nutr 2010;104:503-12.  Back to cited text no. 33
    
34. Boussetta T, Raad H, Lettéron P, Gougerot-Pocidalo MA, Marie JC, Driss F, et al. Punicic acid a conjugated linolenic acid inhibits TNFalpha-induced neutrophil hyperactivation and protects from experimental colon inflammation in rats. PLoS One 2009;4:e6458.  Back to cited text no. 34
    
35. Katz SR, Newman RA, Lansky EP. Punica granatum: Heuristic treatment for diabetes mellitus. J Med Food 2007;10:213-7.  Back to cited text no. 35
    
36. Rock W, Rosenblat M, Miller-Lotan R, Levy AP, Elias M, Aviram M. Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities. J Agric Food Chem 2008;56:8704-13.  Back to cited text no. 36
    
37. Fenercioglu AK, Saler T, Genc E, Sabuncu H, Altuntas Y. The effects of polyphenol-containing antioxidants on oxidative stress and lipid peroxidation in Type 2 diabetes mellitus without complications. J Endocrinol Invest 2010;33:118-24.  Back to cited text no. 37
    
38. Rasheed Z, Akhtar N, Haqqi TM. Pomegranate extract inhibits the interleukin-1b-induced activation of MKK-3, p38a-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes.-Arthritis Res Ther 2010;12:195.  Back to cited text no. 38
    
39. Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D. A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 1994;372:739-46.  Back to cited text no. 39
    
40. Kumar S, Votta BJ, Rieman DJ, Badger AM, Gowen M, Lee JC. IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase. J Cell Physiol 2001;187:294-303.  Back to cited text no. 40
    
41. Loeser RF, Erickson EA, Long DL. Mitogen-activated protein kinases as therapeutic targets in osteoarthritis. Curr Opin Rheumatol 2008;20:581-6.  Back to cited text no. 41
    
42. Hayden MS, Ghosh S. Signaling to NF-B. Genes Dev 2004;18:2195.  Back to cited text no. 42
    
43. Schieven GL. The biology of p38 kinase: A central role in inflammation. Curr Top Med Chem 2005;5:921-8.  Back to cited text no. 43
    
44. 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;5:9.  Back to cited text no. 44
    
45. Lansky E, Shubert, S, Neeman I. Pharmacological and therapeutic properties of pomegranate. Israel: CIHEAM-Options Mediterraneennes; 2004;42:231-5.  Back to cited text no. 45
    
46. Satish S, Mohana D, Ranhavendra M, Raveesha K. Antifungal activity of some plant extracts against important seed borne pathogens of Aspergillus sp. J Agric Sci Technol 2007;3:109-19.  Back to cited text no. 46
    
47. Mithun P, Prashant G, Murlikrishna K, Shivakumar K, Chandu G. Antifungal efficacy of Punica granatum, Acacia nilotica, Cuminum cyminum and Foeniculum vulgare on Candida albicans: An in vitro study. Indian J Dent Res 2010;21:334-6.  Back to cited text no. 47
    
48. Höfling JF, Anibal PC, Obando-Pereda GA, Peixoto IA, Furletti VF, Foglio MA, Goncalves RB. Antimicrobial potential of some plant extracts against Candida species. Braz J Biol 2010;70:1065-8.  Back to cited text no. 48
    
49. Ferrara AM. Treatment of hospital-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 2007;30:19-24.  Back to cited text no. 49
    
50. Wenzel RP, Bearman G, Edmond MB. Community-acquired methicillin-resistant staphylococcus aureus (MRSA): New issues for infection control. Int J Antimicrob Agents 2007;30:210-2.  Back to cited text no. 50
    
51. 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 2009;9:23.  Back to cited text no. 51
    
52. Sharma M, Li L, Celver J, Killian C, Kovoor A, Seeram NP. Effects of fruit ellagitannin extracts, ellagic acid, and their colonic metabolite, urolithin A, on Wnt signaling. J Agric Food Chem 2010;58:3965-9.  Back to cited text no. 52
    
53. 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;18:553-61.  Back to cited text no. 53
    
54. Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH. Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Exp Dermatol 2010;19:e182-90.  Back to cited text no. 54
    
55. Pai MB, Prashant GM, Murlikrishna KS, Shivakumar KM, Chandu GN. Antifungal efficacy of Punica granatum, Acacia nilotica, Cuminum cyminum and Foeniculum vulgare on Candida albicans: An in vitro study. Indian J Dent Res 2010;21:334-6.  Back to cited text no. 55
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56. Bhadbhade SJ, Acharya AB, Rodrigues SV, Thakur SL. The antiplaque efficacy of pomegranate mouthrinse. Quintessence Int 2011;42:29-36.  Back to cited text no. 56
    
57. Menezes SM, Cordeiro LN, Viana GS. Punica granatum (pomegranate) extract is active against dental plaque. J Herb Pharmacother 2006;6:79-92.  Back to cited text no. 57
    
58. Promprom W, Kupittayanant P, Indrapichate K, Wray S, Kupittayanant S. The effects of pomegranate seed extract and beta-sitosterol on rat uterine contractions. Reprod Sci 2010;17:288-96.  Back to cited text no. 58
    
59. Kishore RK, Sudhakar D, Parthasarathy PR. Embryo protective effect of pomegranate (Punica granatum L.) fruit extract in adriamycin-induced oxidative stress. Indian J Biochem Biophys 2009;46:106-11.  Back to cited text no. 59
    
60. Türk G, Sönmez M, Aydin M, Yüce A, Gür S, Yüksel M, et al. Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clin Nutr 2008;27:289-96.  Back to cited text no. 60
    
61. Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, et al. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease. Neurobiol Dis 2006;24:506-15.  Back to cited text no. 61
    
62. Dell'Agli M, Galli GV, Corbett Y, Taramelli D, Lucantoni L, Habluetzel A, et al. Antiplasmodial activity of Punica granatum L. fruit rind. J Ethnopharmacol 2009;125:279-85.  Back to cited text no. 62
    
63. Dell'agli M, Galli GV, Bulgari M, Basilico N, Romeo S, Bhattacharya D, et al. Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria. Malar J 2010;9:208.  Back to cited text no. 63
    
64. Neurath AR, Strick N, Li YY, Debnath AK. Punica granatum (pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide. Ann N Y Acad Sci 2005;1056:311-27.  Back to cited text no. 64
    
65. Pirbalouti AG, Azizi S, Koohpayeh A, Hamedi B. Wound healing activity of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats. Acta Pol Pharm 2010;67:511-6.  Back to cited text no. 65
    
66. Pirbalouti AG, Koohpayeh A, Karimi I. The wound healing activity of flower extracts of Punica granatum and Achillea kellalensis in Wistar rats. Acta Pol Pharm 2010;67:107-10.  Back to cited text no. 66
    
67. Hayouni E, Miled K, Boubaker S, Bellasfar Z, Abedrabba M, Iwaski H. Hydroalcoholic extract based-ointment from Punica granatum L. peels with enhanced in vivo healing potential on dermal wounds. Phytomedicine 2011;18:976-84.  Back to cited text no. 67
    
68. Gil MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000;48:4581-9.  Back to cited text no. 68
    
69. Tao X, Schulze-Koops H, Ma L, Cai J, Mao Y, Lipsky PE. Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production. Arthritis Rheum 1998;41:130-8.  Back to cited text no. 69
    
70. Cerdá, B, Cerón JJ, Tomás-Barberán FA, Espín JC. Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to rats for 37 days is not toxic. J Agric Food 2003;51:3493-501.  Back to cited text no. 70
    
71. Prescott SM, Fitzpatrick FA. Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta 2000;1470: 69-78.  Back to cited text no. 71
    
72. Mena P, Girones-Vilaplana A, Moreno Diego A, García-Viguera C. Pomegranate fruit for health promotion: Myths and realities. Funct Plant Sci Biotechnol 2011;5:33-42.  Back to cited text no. 72
    
73. Shravan Kumar Y, Adukondalu D, Bhargavi Latha A, Vamshi Vishnu Y, Ramesh G, Shiva Kumar R, et al. Effect of pomegranate pretreatment on the oral bioavailability of buspirone in male albino rabbits. Daru 2011;19:266-9.  Back to cited text no. 73
    
74. Nagata M, Hidaka M, Sekiya H, Kawano Y, Yamasaki K, Okumura M, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab Dispos 2007;35:302-5.  Back to cited text no. 74
    
75. Misaka S, Nakamura R, Uchida S, Takeuchi K, Takahashi N, Inui N, et al. Effect of 2 weeks' consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: An open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther 2011;33:246-52.  Back to cited text no. 75
    
76. Vidal A, Fallarero A, Peña BR, Medina ME, Gra B, Rivera F, et al. Studies on the toxicity of Punica granatum L. (Punicaceae) whole fruit extracts. J Ethnopharmacol 2003;89:295-300.  Back to cited text no. 76
Advanced Biomedical Research
Volume 2014, March
March 2014
Pages 1-8