Ancient Seed for Modern Cure - Pomegranate Review of Therapeutic Applications in Periodontics.

Punica granatum (pomegranate), the member of Punicaceae family, is used in the prevention and treatment of health disorders. P. granatum contains diverse range of phytochemicals including ellagic acid, punicalagin, pedunculagin, quercetin, rutin, tannic acid, polyphenol, anthocyanins, and catechins. This review aims at providing an overview of the chemical constituents, antibacterial, anti-inflammatory, and antioxidant properties of P. granatum, and its role in the prevention and treatment of gingival and periodontal diseases.

INTRODUCTION

Periodontitis is a common disease which leads to loss of supporting structures around tooth which eventually causes tooth loss. The destructive pathway involves both plaque bacterial products and the host inflammatory and immune responses. Scaling and root planing is not sufficient for complete elimination of the periodontal microflora. Hence, the administration of pharmacologic agents (antiseptics, nonsteroidal anti-inflammatory drugs, and antibiotics) is employed as an additional treatment protocol to ensure eradication of the microorganisms. When such drugs are systemically given at larger doses, there will be complications such as antibiotic resistance and unwanted effects such as drug interactions. These drawbacks led to the development of local drug delivery system. Even though many variants of these drugs are available in the market such as gels, strips, microcapsules, fibers, and film, there is a need for natural products since it avoids the risk and complications of systemic drugs.

Pomegranate extracts are one among the many herbs that are available and have been reported to have huge medical value.[1] In ayurvedic medicine, the pomegranate is seen as “a pharmacy unto itself “ and is used as a “blood tonic,” to heal many health problems. The polyphenols which are extracted from the pomegranate have many good properties such as antibacterial,[2] antioxidant,[3] anti-inflammatory,[4] antiproliferative,[5] and DNA repair activities and thus can be used as a good alternative for systemic drugs.

PUNICA GRANATUM

The pomegranate, Punica granatum L., an ancient and highly distinctive fruit, is the member of the Punicaceae family.[6] The genus name, Punica, in Roman means carthage, where the best pomegranates were known to grow. Granatum is known in French as grenade, in Spanish as granada, and literally translates to seeded (“granatus”) apple (“pomum”).[7] It is a large shrub which grows 12–16 feet and has many spiny branches. The leaves are glossy, lance shaped, and the flowers are large, red, white, or variegated and have a tubular calyx that eventually becomes the fruit. The matured pomegranate fruit is grenade shaped, deep red, and has a leathery skin topped by a calyx. The fruit contains many seeds (arils) which are separated by white, membranous pericarp.[8]

CHEMICAL COMPOSITION OF P

Pomegranate is rich in polyphenols such as ellagitannins, punicalagins, punicallin, and gallotannin. Pomegranate pericarp (peel, rind) contains phenolic punicalagin; gallic acid and other fatty acid; catechin, quercetin, rutin, and other flavones; flavanones; and anthocyanidins. The leaves of pomegranate contains tannins (punicalin and punicafolin), flavones and glycosides.[9] Pomegranate flowers have gallic acid, ursolic acid, and triterpenoids, including maslinic and asiatic acid. Pomegranate roots and bark show the presence of ellagitannins, including punicalin and punicalagin and numerous piperidine alkaloids.

Pomegranate fruit (50%) components comprise 40% arils and 10% seeds. Fruit contains components such as corilagin, ellagic acid, kaempferol, luteolin, myricetin, and quercetin. Seed oil contains linoleic acid, linolenic acid, oleic acid, palmitic acid, stearic acid, cholesterol, estriol, and testosterone.[10]

P GENERAL HEALTH

P. granatum has many beneficial effects on general health including antioxidant, antibacterial, antiviral, and anti-inflammatory properties. It has also potent anticancer and immune-modulating effects.[11] Pomegranate lowers cholesterol and other cardiac risk factors and also lowers blood pressure. P. granatum inhibits abnormal platelet aggregation and decreases the risk of heart attacks, strokes, and embolic diseases. It has therapeutic effect against certain diseases and conditions such as depression, osteoporosis, asthma, dysentery, obesity, and Alzheimer's disease. The pomegranate has also been found to be a source of protection for skin diseases.

P IN DENTAL HEALTH

Pomegranate has an antibacterial effect against Plaque forming bacteria, antiviral efficacy against herpes simplex virus, and antioxidant, and it has a potent anti-inflammatory property. P. granatum has shown to reduce the gingival bleeding and decreases the risk of periodontal disease progression. It has excellent wound healing property and has been widely used in mouth lesions, denture stomatitis and ulcers, etc.

ROLE OF PUNICALAGIN IN PERIODONTAL DISEASE

Antibacterial effect

Pomegranate extract exerts antibacterial activity against periodontal pathogens by reacting with sulfhydryl groups and oxidizing the enzymes present in the bacteria and through more nonspecific reaction with proteins. Punicalagin also prevents the development of antibiotic resistance. The primary colonizer in dental plaque formation is Streptococcus sanguis and it is sensitive to pomegranate extract. Pereira et al., 2006,[2] demonstrated that pomegranate had more inhibitory effect against S. sanguis, Streptococcus sobrinus, and Lactobacillus casei when compared to chlorhexidine mouth rinse. Kote et al., 2011,[12] also reported that Pomegranate mouth rinse inhibits plaque-forming bacteria by 84% in comparison to chlorhexidine mouth rinse (79%). Therefore, punicalagin could be a possible alternative to prevent the formation of plaque on the tooth surface.

Abdollahzadeh et al., 2011,[13] in a study reported that antibacterial effect of pomegranate is because of the presence of hydrolysable tannins and polyphenols such as punicalagin and gallic acid. These specific components act on bacterial cell membrane and increase the bacterial cell wall breakage, prevent adhesion of bacteria to the tooth surface, precipitate the protein, and inhibit several bacterial enzymes. In a study done by Bhadbhade et al., 2011,[14] the growth of anaerobic periodontal pathogens such as Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Porphyromonas gingivalis has been shown to be inhibited by pomegranate mouthwash. The study also demonstrated that pomegranate extract as a mouthwash resulted in more reduction of gingival and bleeding scores when compared to chlorhexidine mouthwash.

Probiotic bacteria could be beneficial in treating periodontitis by not only decreasing the periodontal pathogen burden in the oral biofilm but also by strengthening epithelial barrier function, thus enhancing resistance to infections. Punicalagin has been shown to increase probiotic bacteria, especially Bifidobacterium species and Lactobacillus species.[15]

ANTIVIRAL PROPERTY

Pomegranate extracts have shown to be effective against herpes virus.[16] Herpes viruses may initiate and accelerate progression of periodontitis due to its potential to stimulate cytokine release from host cells, impaired host defense mechanisms, resulting in increased virulence of resident periodontopathic bacteria.[17] Hence, pomegranate with its antiviral property could cure periodontitis as well. A study done by El-Sherbini and Shoukry[18] concluded that pomegranate peel extract had a significant effect on Trichomonas tenax and could be used in the treatment of acute ulcerative gingivitis.

ANTI-INFLAMMATORY PROPERTY

Cyclooxygenase and lipoxygenase in COX pathway are involved in production of various inflammatory mediators. The anti-inflammatory action of punicalagin is exerted by the inhibition of nuclear factor kappa B (NF-κB) activity and by the prevention of ERK-1 or ERK-2 (mitogen-activated protein kinase cascades) activation. Lee et al., 2010,[19] also demonstrated that pomegranate extracts inhibited nitric oxide (NO) production by RAW 264.7 macrophage cells. Pomegranate extract also has been shown to inhibit inducible nitric oxide synthase expression. Thus, it has the property of inhibiting matrix metalloproteinase expression, prostaglandin E2 production, and interleukin-1beta (IL-1B)-induced tissue destruction in periodontitis.

Gracious Ross Ross et al., 2001,[20] has reported that punicalagin can regulate the action of macrophages and T and B lymphocytes. The study done by Pereira et al. 2006[2] showed a significant reduction of gingival bleeding after the use of a pomegranate dentifrice. It has also been demonstrated that the polyphenols from pomegranate extract have an inhibitory effect on IL-6 and IL-8 expression through modulation of the activation and DNA-binding activity of NF-κB. Therefore, punicalagin could be useful to treat gingivitis and periodontitis through its excellent anti-inflammatory properties.

ANTIOXIDANT PROPERTIES

Punicalagin is the main ingredient present in pomegranate peel as evaluated by ferric reducing antioxidant power assay and was found to be the richest source of antioxidants. Ismail et al., 2012,[21] reported that punicalagin composes 85% of the total pomegranate tannins and accounts for more than 50% of the antioxidant activity of pomegranate juice. Xu et al., 2014,[22] reported that punicalagin shows an antioxidant activity by increasing Nrf2-mediated HO-1 expression and also induces the PI3K/Akt-mediated HO-1 expression. Punicalagin enhances the SOD1 mRNA expression and thereby inhibits reactive oxygen species generation and NO overproduction by macrophages. The antioxidant activity of punicalagin acts by electron donation to free radicals that convert them to relatively more stable compounds. Gil et al., 2000,[23] reported that punicalagin exhibits 3-fold antioxidant effect than that of green tea and red wine.

WOUND HEALING PROPERTY

Morgan and Nigam, 2013,[24] reported that the wound healing properties of the pomegranate extract are due to the presence of tannins and polyphenols. It is known to induce fibroblast migration and proliferation, collagen formation, and angiogenesis. Nema et al., 2013,[25] reported that 5%, 10%, and 15% methanol peel extract ointment of pomegranate gives a complete and faster wound healing. Improved epithelialization and contraction of incised wounds, along with increased hydroxyproline content, dry weight, and breaking strength of granulated tissues, can be observed in the healing process of pomegranate-treated wounds.

CONCLUSION

In the recent years, the use of plants with preventive and therapeutic effects contributes to the interest in phytotherapy due to the development of microbial resistance to antibiotics, and consumers becoming aware of the adverse effects associated with traditional antibiotics. Thus, pomegranate referred as the “Nature's power fruit” is a phytochemical reservoir of heuristic medicinal value. Pomegranate with its potent antibacterial, antiviral, antioxidant, anti-inflammatory, wound healing, and probiotic properties could prove truly as a “Pharmacy unto itself” for the treatment of periodontal diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.