**6. Conclusion**

354 Cancer Prevention – From Mechanisms to Translational Benefits

(chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin) was noted in the *S. aureus* isolates, synergy with ampicillin was the most pronounced. A combination of the two increased the lag time to bacterial growth by three hours and was also bacteriocidal as evidenced by a 72.5% reduction in methicillin-sensitive organisms and a 99.9% reduction in MRSA. Bialonska et al. (2009b) stated that commercial extract of pomegranate by-product provided by POM Wonderful (Los Angeles, CA) and punicalagins inhibited the growth of pathogenic clostridia and *S. aureus*. Nevertheless the probiotic lactobacilli and bifidobacteria were not affected by ellagitannins. These findings lead to the conclusion that the growth inhibition toward pathogenic bacteria could be attributed to the accumulation of ellagitannins in the large intestines, where they interact with complex gut microflora, and

Su et al. (2010) stated that the combination of pomegranate juice and pomegranate polyphenols was also effective against food-borne viral infectivity and appear to be promising natural remedies for preventing or reducing human norovirus infections. In addition, pomegranate purified polyphenol extract inhibited influenza virus having also a synergistic effect with oseltamivir, since influenza continues to be a major cause of mortality and morbidity eventhough the applications of the vaccines and antiviral therapies (Haidari

Johann et al. (2010) studying the activity of extracts of some plants used in Brazilian traditional medicine against the pathogenic fungus that causes this Paracoccidioidomycosis, *Paracoccidioides brasiliensis*, reported that the hexane extract of pomegranate stem exhibited better antifungal activity against the three clinical isolated than other parts of the plant or

*Candida* species, a normal component of the human biota in the gastrointestinal tract and oral and vaginal mucosa, can cause superficial infections such as thrush and vaginitis. Endo et al. (2010) reported that punicalagin isolated from pomegranate peels possessed strong activity against *Candida albicans* and *C. parapsilosis* as well as the combination of punicalagin and fluconazole showed a synergistic interaction. Tayel & El-Tras (2009) demonstrated that methanol, ethanol and water extracts of pomegranate peels were effective against *C. albicans*  growth. In addition, they also proved that pomegranate peel extract aerosol was an efficient method for complete sanitizing of semi-closed places against *C. albicans* growth, and thereby could contribute for preventing *C. albicans* contamination and growth in suspected places. Ethnobotanical studies performed in Brazil had demonstrated the utilization of pomegranate in oral health since denture stomatitis is commonly associated with *C. albicans* 

Dell'Agli et al. (2009) studied the *in vitro* antiplasmodial and antimalarial activity of methanolic extracts of a tannin-enriched fraction and of metabolites to estimate their curative efficacy and mechanisms of action. They conclude that methanolic extracts of pomegranate inhibited *Plasmodium falciparum* and *P. vivax* growth *in vitro*, and suggested that these might be attributed to the low bioavailability as well as the kinetic of conversion

Pomegranate and its products have a long history of use as food or ethnic medicine without adverse effects, and also it has GRAS (generally recognized as safe) status in the

lower media pH due to the presence of punicalagins.

and some other *Candida* species (Santos et al., 2009).

of ellagic acid to inactive metabolites urolithins.

**5. Adverse effects and reactions/safety** 

et al., 2009).

other fractions of the same plant.

Nowadays, it is widely accepted that the beneficial health effects of fruits and vegetables in the prevention of diseases are due to the bioactive compounds they contain.

Based on the explosion of interest in the numerous therapeutic properties over the last decade and *in vitro*, animal, and clinical trials pomegranate seems to be a promising food with well-defined therapeutic benefits. The epidomiological data suggests that the pomegranate fruit and its associated bioactive compounds such as phenolic acids, flavonoids, and tannins may possess a strong potential as a chemopreventive and possibly as new tools for preventive and possibly therapeutic interventions against various human cancers. This could have a direct practical implication to cancer patients if consumption of fruits like pomegranate can inhibit the process of carcinogenesis. Further studies should focus on the potential clinical usefulness of the agent through issues such as determining the optimal period and route of administration, systemic bioavailability, potent anticancer activity, optimal dosing and toxicity (if any) of the agent and single or combinatorial approach. In addition, the possible use of pomegranate extracts as a therapy or adjunct for prevention and treatment of several disease processes, such as diabetes, cardiovascular disease, atherosclerosis, inflammation, microbial infection, obesity, male infertility, Alzheimer underscores the need for more clinical research. Therefore, ongoing studies should focus on developing novel pomegranate derived products such as ready-to-eat pomegranate seeds, single-strength juices, juice concentrates, seeds in syrup, frozen seeds, and traditional products such as pomegranate pekmez, leather and molasses, to benefit from these constituents throughout a healthy life cycle.
