Trial Information

The Clinical Efficacy of Topical Nasal Pomegranate Fruit Extract (PFE) for Patients With Chronic Rhinitis, Chronic Sinusitis With or Without Nasal Polyps

There are many publications indexed by Medline dealing with pomegranate and Punica granatum
and there is interest in pomegranate as a medicinal and nutritional product.

The pomegranate tree, Punica granatum, especially its fruit, possesses a vast ethnomedical
history and represents a phytochemical reservoir of heuristic medicinal value. The
tree/fruit can be divided into several anatomical compartments: (1) seed,(2) juice, (3)
peel, (4) leaf, (5) flower, (6) bark, and (7) roots, each of which has interesting
pharmacologic activity. Juice and peels, for example,possess potent antioxidant properties,
while juice, peel and oil are all weakly estrogenic and heuristically of interest for the
treatment of menopausal symptoms and sequelae. The use of juice, peel and oil have also been
shown to possess anticancer activities, including interference with tumor cell
proliferation, cell cycle, invasion and angiogenesis. These may be associated with plant
based anti-inflammatory effects. The phytochemistry and pharmacological actions of all
Punica granatum components suggest a wide range of clinical applications for the treatment
and prevention of chronic inflammation.

Pomegranate as few medical applications as gastrointestinal infections, oral wounds and
others. There is a publication on the positive use of pomegranate, in reducing of trigeminal
pain post Herpes Zoster infection (1). Another work described the synergistic effect of
pomegranate extraction and antibiotics for Staphyloccocus Areus (2). Pomegranate extraction
was used for viral delay of HIV I in AIDS patients (3).

It's antiviral effect was examined against HSV and RSV (6). There was a positive effect on
H7 -E. COLI 0157(4). Pomegranate extraction was found to help as antibacterial effect as
other Mexican extraction drugs, for Gastrointestinal infections (5). High concentrations of
phenol substances was evaluated in wound healing and it was efficient (7). Methanolic
substances from pomegranate extraction was evaluated and found efficient for all the
bacteria that was examined (8). Recently pomegranate extraction was found active in
antibacterial effect and in synergism with tetracyclin against staphyloccocus Areus with
Methicillin resistance (MRSA).

Pomegranate polyphenol extract (PPE) has anti-influenza properties. Using real time PCR,
plaque assay, and TCID 50% hemagglutination assay, the investigators have shown that PPE
suppresses replication of influenza A virus in MDCK cells. PPE inhibits agglutination of
chicken red blood cells (cRBC) by influenza virus and is virucidal. The single-cycle growth
conditions indicated that independent of the virucidal effect PPE also inhibits viral RNA
replication. PPE did not alter virus ribonucleoprotein (RNP) entry into nucleus or
translocation of virus RNP from nucleus to cytoplasm in MDCK cells. The investigators
evaluated four major Polyphenols in PPE (ellagic acid, caffeic acid, luteolin, and
punicalagin) and demonstrated that punicalagin is the effective, anti-influenza component of
PPE. Punicalagin blocked replication of the virus RNA, inhibited agglutination of chicken
RBC's by the virus and had virucidal effects. Furthermore, the combination of PPE and
oseltamivir synergistically increased the anti-influenza effect of oseltamivir. In
conclusion, PPE inhibited the replication of human influenza A/Hong Kong (H3N2) in vitro.
Pomegranate extracts should be further studied for therapeutic and prophylactic potential
especially for influenza epidemics and pandemics.

Commonly found in many plants, ellagic acid exhibits powerful anticarcinogenic and
antioxidant properties, propelling it to the forefront of pomegranate research. Many
commercially available pomegranate extracts are being standardized to contain 40-percent (or
more) ellagic acid. Lansky's research confirms the synergistic action of several pomegranate
constituents is superior to ellagic acid in suppressing prostate cancer. To quote Lansky,
"The recent profusion onto the nutraceuticals marketplace of products standardized to 40
percent (or even higher) ellagic acid represents a cynical, lucre-driven attempt to replace
the power of the pomegranate with the power of ellagic acid. The pomegranate needs no such
tricks or enhancements. It is rather an extraordinary, albeit mysterious (and messy), fruit
with a complete medicinal power contained within its juice, peel, and seeds.

Topical applications of pomegranate preparations have been found to be particularly
effective for controlling oral inflammation, as well as bacteria and fungal counts in
periodontal disease and Candida-associated denture stomatitis. A hydroalcoholic extract of
Punica granatum fruit (HAEP) was investigated for antibacterial effect on dental plaque
microorganisms. Sixty healthy patients (33 females/27 males; ages 9-25) with fixed
orthodontic appliances were randomized to three groups of 20:

(1) control group who rinsed with 15 mL distilled water; (2) a group who rinsed with 15 mL
chlorhexidine, a standard antiplaque mouth rinse; and (3) a group who rinsed with a 15-mL
HAEP solution. HAEP decreased the number of colony forming units (CFU) of dental plaque
bacteria 84 percent, comparable to chlorhexidine (79-percent inhibition) but significantly
better than the control rinse (11-percent inhibition). Both HAEP and chlorhexidine were
effective against Staphylococcus, Streptococcus, Klebsiella, and Proteus species, as well as
E. coli. The ellagitannin, punicalagin, is thought to be the fraction responsible for
pomegranate's antibacterial activity.

Bacterial Infections The only human trials examining the antibacterial properties of
pomegranate extracts have focused on oral bacteria. However, several in vitro assays
demonstrate its bacteriocidal activity against several highly pathogenic and sometimes
antibiotic-resistant organisms. Brazilian researchers evaluated the synergistic effect of a
P. granatum methanolic extract with five antibiotics on 30 clinical isolates of
methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus.75
Antibiotics tested were chloramphenicol, gentamicin, ampicillin, tetracycline, and
oxacillin. Although synergistic activity between the pomegranate extract and all five
antibiotics was noted in the S. aureus isolates, synergy with ampicillin was the most
pronounced. Based on earlier research and the results of this study, the ellagitannin,
punicalagin, is thought to be the primary constituent responsible for the observed
antibacterial effects. Another organism that can cause significant disease in humans is
enterohemorrhagic Escherichia coli (E. coli O157:H7). An ethanolic PPE, one of the two most
effective extracts against E. coli O157:H7, was shown to be both bacteriostatic and
bacteriocidal, indicating PPE may be an effective adjunct treatment for E. coli O157:H7
infection.

On the above information the investigators will try and evaluate the clinical efficacy of
topical nasal Pomegranate fruit extract (PFE) (Punica Granatum) for patients with Chronic
rhinitis, chronic sinusitis, nasal polyps and chronic rhinitis.