Medical Attributes of Punica granatum – Pomegranate

By Anthony Giuffrida, Amanda Karasinski, Catherine Simone
Wilkes University, Wilkes-Barre, PA

July, 2007
     Punica granatum, commonly known as the pomegranate, is a member of the Punicaceae (Pomegranate family) (CRFG 1997).  The pomegranate is native to Iran and the Himalayas of northern India (CRFG 1997). Individual pomegranates are shrubs or small trees ranging from 20 to 30 feet in height, with many branches, and a life span of up to two centuries (Morton, 1987). The fruit is nearly round measuring 2.5 – 5 in, which is crowned at the base by the prominent calyx (CRFG 1997). The seeds represent 52% of the weight of the whole fruit (Morton, 1987).

     Pomegranate seeds are a source of many nutrients but the pomegranate can also be used for medicinal purposes. The fruit’s medical significance dates back to ancient times and is even noted in Egyptian mythology and art (Morton, 1987). Extracts of the juice, bark, leaves, immature fruit, and fruit rinds have all been noted to have some medical significance, most notably antioxidant activity, antibacterial properties, uses in diabetes, heart disease, and cancer (Morton, 1987).

     The primary bioactive constituents of pomegranate juice are the polyphenols and their potent antioxidant characteristics (Aviram, et.al., 2004). Punicalagin is a major antioxidant polyphenol in pomegranate juice (Seeram et al., 2005). Antioxidant activities were tested in vitro with pomegranate juice, punicalagin, ellagic acid, and total pomegranate tannin (polyphenol extracts from whole pomegranate juice). Results of the experiment identified whole pomegranate juice as having more antioxidant activity than any of its individual constituents. The superiority of pomegranate juice compared to its individual polyphenols provides evidence of the synergy of multiple compounds in comparison to its individual polyphenols (Seeram et al., 2005).

     The antibacterial and antimicrobial properties of Punica granatum have been studied extensively. Extracts from the plant have been found to work against Methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant (MRSA) Staphylococcus aureus, Escherichia coli O157:H7, Salmoneela typhi, and some streptococci strains (Braga, et. al. 2005; Machado, et. al. 2003; Neurath, et. al. 2005; Rani, et. al. 2004; Vasconcelos, et. al. 2006; Voravuthikunchai, et. al. 2004). Thus alternative medicines that incorporate Punica granatum have potential usefulness against bacterial infections.

     An important potential application for the anti-microbial properties of Punica granatum, is its use as a topical microbicide for HIV prevention. In vitro research indicates that an anti-HIV-1 microbicide could potentially be made from Punica granatum (Neurath, et. al. 2005).

     The antibacterial and antimicrobial attributes of Punica granatum may have applicability to the dental field. Punica granatum phytotherapeutic was tested against the streptococci strains S. mutans, S. mitis, and C. albicans. It was effective against the isolated bacteria species, and when tested against an assembly of different microorganisms, the Punica granatum phytotherapeutic gel had greater efficiency in inhibiting microbial adherence to glass than the miconazole (Daktarin oral gel). This suggests that this phytotherapeutic agent might be used to control the adherence of different microorganisms in the oral cavity (Vasconcelos, et. al. 2006). The hydroalcoholic extract (HAE) from Punica granatum was found to be very effective against dental plaque microorganisms in an in vivo study, decreasing the number of colony forming units per milliliter by 84% versus the control group’s 11% decrease (distilled water). This indicates that the HAE may be a possible alternative for the treatment of dental plaque bacteria (Menezes, et. al. 2006).

     An in vivo study was done to test the effects of the combined extracts from Centella asiatica, commonly known as Asiatic Pennywort, and Punica granatum on periodontal healing following scaling and root planning in adult periodontitis patients. The results indicate that local delivery with C. asiatica and P. granatum extracts, plus scaling and root planning, significantly reduced the clinical signs of chronic periodontitis (Sastracha, et. al. 2003).

     Pomegranate fruit extract, has been found to be a source of a skin protection. A study by Syed et al (2006) suggests that pomegranate fruit extract (PFE) is effective for ameliorating UVA-mediated damages by modulating cellular pathways and preventing potential skin cancers.

     Studies have been performed to see if pomegranate can treat or prevent diabetes and heart disease. Esmaillzadeh, et al. (2006) found that pomegranate juice significantly reduced total cholesterol, low-density lipoproteins (LDL), the ratio of LDL/ high- density lipoproteins (HDL), and the ratio of total cholesterol to HDL. These findings show that consumption of the pomegranate juice may modify heart disease risk factors in patients with hyperlipidemia. Sumner, et al. (2005) tested the effects of pomegranate juice in its efforts to help patients with coronary heart disease concluded that daily consumption of pomegranate juice may improve stress-induced myocardial ischemia in patients who have coronary heart disease (CHD). When ingested, pomegranate juice could help patients with carotid artery stenosis, decrease carotid intima-media thickness, and their systolic blood pressure (Aviram, et al.,2004). 

     The juice, peel, and seed oil have been found to have anti-cancer properties that inhibit proliferation, cell cycle, and angiogenesis (Lansky and Newman 2007). Albrecht et al. (2004) studied the effects of pomegranate oil, seed oil, fermented juice polyphenols, and pericarp polyphenols on human prostate cancer cell growth in vivo and found that it demonstrated significant antitumor activity against human prostate cancer. Lansky et al. (2005) utilizing pomegranate fruit extract, showed that cell growth was inhibited and followed by apoptosis of extremely aggressive human prostate carcinoma PC-3 cells. Also, fermented pomegranate juice polyphenols were tested in combination with pericarp polyphenols on the proliferation of DU 145 human prostate cancer cell lines in vitro. Supra-additive and synergistic effects were experimentally proven (Lansky et al., 2005). These studies provide evidence suggesting that consuming pomegranate may delay prostate cancer progression (Malik and Mukhtar 2006).

     Toi et al. (2003) has found that pomegranate seed oil and fermented juice polyphenols tend to inhibit breast cancer cell proliferation, invasion, and promotes apoptosis of breast cancer cells. Kim et al. (2002) reports that fermented pomegranate juice polyphenols consistently showed twice the anti-proliferative effect as fresh pomegranate juice polyphenols. Research on lung cancer looked at the effect of PFE as a source of treatment (Khan et al., 2007). The results suggested that PFE can be a chemopreventative agent against lung cancer (Khan et al. 2007).

     Flavonoid-rich polyphenols can be extracted from fresh and fermented PJ. These polyphenols were tested for their ability to induce differentiation in human HL-60 promyelocytic leukemia cells. Extracts from the fermented juice and pericarps promoted differentiation the best when compared to fresh PJ and had similar inhibitory effects on proliferation of the cell line (Kawaii and Lansky 2004).

     Pomegranate tannin extract and punicalagin were found to suppress the COX-2 protein expression and inhibited phosphorylation and binding of the p65 subunit in HT-29 colon cancer cells indicating that these chemicals could play a major role in modifying the inflammatory cell signaling in colon cancer cells (Adams et al., 2006).

    Clinical research into the effects of the antioxidant polyphenol-rich pomegranate juice (PJ) on chronic obstructive pulmonary disease (COPD) found no differences between the control group and those receiving PJ. The conclusion of the study was that pomegranate juice supplementation (400ml PJ daily) added no benefit to the current therapy standards in patients with COPD (Cerdá, et. al. 2006).

     Pomegranate juice may have potentially dangerous interaction with other medications. Pomegranate juice is known to inhibit intestinal cytochrome P450 3A4. During rosuvastatin treatment for myopathy, PJ may increase the risk of rhabdomyolysis, the breakdown of muscle fibers resulting in the release of muscle fiber contents into the circulation. Some of these are toxic to the kidney and frequently result in kidney damage (Rhabdomyolysis, 2005). However, rosuvastatin is not known to be metabolized by hepatic P450 3A4 (Sorokin, et. al. 2006). Some people are allergic to Punica granatum. Several adverse reactions to pomegranate, including severe symptoms such as anaphylactic shock or laryngeal edema, have been described in recent years. Patients with pomegranate allergy are often sensitized to other allergens. Pomegranate should be considered a potential allergen in patients suffering anaphylaxis in autumn and living in countries where this fruit is consumed (Gaig, et. al. 1999).

      After extensive research on the medicinal properties of pomegranate it is easy to understand why researchers, such as Robert Longtin (2003), have referred to the pomegranate as “nature’s power fruit”. It is rich in antioxidants, has antibacterial properties, has been found useful in treating dental and dermatological conditions, and improves cardiovascular health. Those benefits along with its anticancer capabilities, have compelled researchers to fully investigate the therapeutic uses of pomegranate. This research will hopefully lend insight into new and improved treatment and prevention methods and/ or drugs for a variety of ailments. 

LITERATURE CITED

Adams, L.S., N.P. Seeram, B.B. Aggarwal, Y. Takada, and D. Heber. 2006. Pomegranate juice, totalpomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. Journal of Agriculural Food Chemistry. 54(3): 980-5.

Albrecht, M., W. Jiang, J. Kumi-Diaka, E.P. Lansky, L.M. Gommersall, A. Patel, R.E. Mansel, I. Neeman, A.A. Geldof, and M.J. Campbell. 2004. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. Journal of Medicinal Food. 7(3): 274-283.

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Braga, L.C., A.A. Leite, K.G. Xavier, J.A. Takahashi, M.P. Bemguerer, E. Chartone-Souza, and A.M. Nascimento. 2005. Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus. Canadian Journal of Microbiology 51:541-7.

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Cerdá, B., C. Soto, M.D. Albaladejo, P. Martínez, F. Sanchez-Gascon, F. Thomas-Barberan, and J.C. Espin. 2006. Pomegranate juice supplementation in chronic obstructive pulmonary disease: A 5-week randomized, double-blind, placebo-controlled trial. European Journal of Clinical Nutrition 60(2): 245-53.

Esmaillzadeh A., F. Tahbaz, I. Gaieni, H. Alavi-Majd, and L. Azadbakht. 2006. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. International Journal Vitamin Nutritional Resources. 76(3): 147-51.

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Kawaii, S. and E.P. Lansky. 2004. Differentiation-promoting activity of pomegranate fruit extracts in HL-60 human promyelocytic leukemia cells. Journal of Medicinal Food. 7(1): 13-18.

Khan, N, N. Handi, F. Afaq, D.N. Syed, M.H. Kweon, H. Mukhtar. 2007. Pomegranate fruit extracts inhibits prosurvival pathways in human A549 lung carcinoma cells and tumor growth in athymic nude mice. Carcinogenesis. 28(1): 163-173.

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Voravuthikunchai, S., A. Lortheeranuwat, W. Jeeju, T. Sririrak, S. Phongpaichit, and T. Supawita. 2004. Effective medicinal plants against enterohaemorrhagic Escherichia coli O157:H7. Journal of Ethnopharmacology 94(1):49-54.
This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 2007. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.

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This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.