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Punica granatum: A review on its potential role in treating periodontal disease

J Indian Soc Periodontol. 2014 Jul-Aug; 18(4): 428432.

PMCID: PMC4158581

doi: 10.4103/0972-124X.138678

Punica granatum: A review on its potential role in treating periodontal disease


Divyashree Prasad and Ravi Kunnaiah
Department of Periodontics, MES Dental College and Hospital, Perintalmanna, Mallapuram, Kerala, India
Address for correspondence: Dr. P. Divyashree, Department of Periodontics, MES Dental College and Hospital, Kolathur via, Palachode.
P.O., Malaparamba, Perintalmanna, Mallapuram District, Kerala - 679 338, India. E-mail: divya_prasad44@yahoo.com
Received 2012 Dec 31; Accepted 2013 Nov 5.
Copyright : Journal of Indian Society of Periodontology
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported,
w hich permits unrestricted use, distribution, and reproduction in any medium, provided the original w ork is properly cited.

Abstract
A wide variety of plants possess enormous treasure of medicinal value. Majority of these medicinal plants have
been used to treat various systemic conditions successfully. Over the recent years, use of these medicinal plants
has resurfaced to treat oral conditions. Among the oral conditions, periodontal disease remains one of the most
common. Alternative and preventive options has become the need of the hour in order to overcome the adverse
effects of the antimicrobial agents used in large as an adjunct to mainstream periodontal treatment. Punica
granatum (Pomegranate) is one of the oldest edible fruit which has a long history as a medicinal fruit. This review
is an attempt to highlight the potential of Punica granatum as a preventive and therapeutic aid to periodontal
disease.
Keywords: Gingivitis, Periodontal therapy, Periodontitis, Pomegranate, Punica granatum
INTRODUCTION
Gingivitis is inflammation of the gingiva. It is defined as the inflammation of the gingiva in which the junctional
epithelium remains attached to the tooth at the original level.[1] Plaque is a requirement for the development of
gingivitis.[2] Periodontitis is a complex disease in which disease expression involves intricate interactions of the
biofilm with the host inflammatory response and subsequent alterations in bone and connective tissue metabolism.
[3] Loss of connective tissue attachment to the teeth is the clinical feature which differentiates periodontitis from
gingivitis.[2]
Plaque control is the primary preventive measure to prevent the onset of gingivitis and arrest its progression into
periodontitis.[1] Although mechanical plaque control methods are efficient in maintaining adequate levels of oral
hygiene, studies have shown that patient compliance in following these methods are not adequate in a large
population.[1] In order to overcome the shortcomings of mechanical plaque control methods, various
chemotherapeutic agents have been employed and developed to improve the efficacy of daily oral hygiene.[1]
Chemotherapeutic agents including systemic antibiotics, antiseptic mouthwashes, local drug delivery of antiseptics
and antibiotics, host modulating agents have been used as an adjunct to the conventional periodontal therapy.[1,4]
The search for newer and safer adjunctive therapeutic agents is still ongoing.
Herbs are nature's gift to humans. They have various bioactive components which possess enormous medicinal
value with least side effects.[5] Synthetic antimicrobial agents and antibiotics are known to cause antimicrobial
resistance, emergence of previously uncommon infections probably due to the inappropriate or widespread
overuse of antimicrobials. Natural phytochemicals have proven to be good alternatives to such synthetic agents.[6]
Natural products like Curcuma zedoaria, calendula, aloe vera and other herbs have been used effectively to treat
oral diseases in the past.[1]

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Description of Punica granatum

Punica granatum belonging to family Punicaceae is more commonly known as pomegranate.[7] The genus name,
Punica, was derived from the roman name for Carthage. The word Pomegranate means Apple (pomum) and
seeded (granatus).[8]
The Punica granatum (hereafter referred to as pomegranate) is a large shrub which grows 12-16 feet, has many
spiny branches with lance shaped glossy leaves. The bark of the tree turns gray as the tree ages. The flowers are
large, red, white, or variegated having a tubular calyx that eventually becomes the fruit. The ripe fruit is about five
inches wide with a deep red, leathery skin, grenade shaped with a pointed calyx. The fruit contains many seeds
separated by white, membranous pericarp. Each seed is surrounded by tart and red juice.[8]
Phytochemistry and functional components

Pomegranate juice contains anthocyanins, glucose, ascorbic acid, ellagic acid, gallic acid, caffeic acid, catechin,
epigallocatechin, quercetin, rutin, iron and amino acids possessing anti-atherosclerotic, antihypertensive, antiaging
and potent antioxidative properties. Seed oil is composed mainly of punicic acid and sterols having
nephroprotective properties. The pericarp (peel, rind) contains punicalagins, flavones, flavonones, and other
flavanols possessing anti-inflammatory, antimutagenic and antifungal activity. Tannins including punicalin and
punicafolin, and flavones glycosides like luteolin and apigenin, form the major constituents of pomegranate leaves.
[9] The leaves are said to have excellent antioxidant properties.[10] The flowers contain ursolic acid, triterpenoids
like maslinic acid and asiatic acid possessing antioxidant, hepatoprotective properties and are used as a remedy
for diabetes mellitus.[9,11] Ellagitannins and piperidine alkaloids are present in pomegranate roots and bark. The
bark possesses molluscicidal properties.[9] The bark and roots are known for its antihelmintic and vermifuge
properties.[12] The most beneficial components of pomegranate are ellagitannins, punicic acid, flavonoids,
anthocyanidins, anthocyanins and estrogenic flavones.[9]
General therapeutics of pomegranate

Pomegranate is considered A pharmacy unto itself.[8] Pomegranate has many potential effects including
bactericidal, antifungal, antiviral, immune modulation, vermifuge, stimulant, refrigerant, astringent, stomachic,
styptic, laxative, diuretic and antihelminthic. It has also been widely used in treatment of cardiovascular diseases,
diabetes, diarrhea, dysentery, asthma, bronchitis, cough, bleeding disorders, fever, inflammation, acquired immune
deficiency syndrome, dyspepsia, ulcers, bruises, sores, mouth lesions, skin lesions, malaria, prostate cancer,
atherosclerosis, hypertension, hyper lipidemia, denture stomatitis, male infertility, vaginitis, erectile dysfunction,
Alzheimer's disease, obesity, and neonatal hypoxic-ischemic brain injury.[6,8,13,14]
Periodontal implication of pomegranate

Dental plaque is a prerequisite for periodontal disease. Bacteria present in dental plaque have direct pathologic
effect on the periodontal tissues. Periodontitis has been proven to occur due to various other indirect mechanisms
apart from the direct effect of periodontal pathogens.[15] Bacterial lipopolysaccharides stimulate production of
catabolic cytokines and inflammatory mediators including arachidonic acid metabolites such as prostaglandin E2
(PGE2), Interleukin-1 (IL-1), Interleukin-6 (IL-6), TNF (Tumour Necrosis Factor). These cytokines and
inflammatory mediators stimulate the release of tissue-derived enzymes, the matrix metalloproteinases, which cause
destruction of the extracellular matrix and bone.[15]
Reactive oxygen species have also been considered as a major etiology of exaggerated inflammatory response in
the pathogenesis of periodontitis. These reactive oxygen species along with direct tissue damage to the
periodontium may also activate key nuclear transcription factors, such as receptor activator of nuclear factor
kappa (NF-B) and Activated Protein-1 (AP-1). These nuclear transcription factors possess a positive effect
on gene transcription for key pro-inflammatory mediators and osteoclastogenesis stimulation.[15]
The major ingredient of pomegranate fatty acids, punicic acid, is an excellent anti-inflammatory compound with a
property to suppress prostaglandin production.[16] Cold pressed pomegranate seed oil has inhibited both
cyclooxygenase and lipoxygenase enzymes in vitro. Both these are key enzymes in production of various
inflammatory mediators.[8] Pomegranate fruit extract has a broad inhibitory effect on matrix metalloproteinaises
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(MMPs) expression and IL1 induced tissue destruction.[8] Apart from the above mechanisms, antiinflammatory effect of pomegranate could be due its immunoregulatory action on macrophages and T and B
lymphocytes.[17]
Pomegranate extract exhibited anti-inflammatory activity through inhibition of NF-B (nuclear factor kappa-B)
activity and prevention of ERK-1 or ERK-2 (Mitogen activated protein kinase cascades) activation. It also
decreased NO (nitric oxide) and PGE2 synthesis in human intestinal Caco-2 cells. Ellagic acid inhibited NF-B
activation through a mechanism independent of I-B (inhibitor of nuclear factor kappa B) phosphorylation.[16]
Blocking NF-B, inflammatory cell signaling pathways that produce various destructive factors may be a potential
strategy to prevent inflammation induced bone resorption and a promising mechanism to treat periodontitis.[15,18]
Oral ingestion of polyphenol rich extract of pomegranate fruit extract inhibited COX-1 and COX-2 enzymes. It
also inhibited IL-1 induced NO and PGE2 production.[19] A significant reduction of gingival bleeding was
observed after using a dentifrice containing pomegranate.[20] Pomegranate could be beneficial in treating
periodontitis as it possesses excellent anti-inflammatory effect.
Pomegranate extracts have the ability to scavenge free radicals and decrease macrophage oxidative stress and
lipid peroxidation.[8] Pomegranate could produce an anti-gingivitis effect as the flavonoids possess direct
antioxidant properties[21] and indirect effects by enhancing the free radical scavenging activity of hepatic enzymes
catalase, super oxide dismutase and peroxidase.[8]
Sastravaha et al. concluded in their preliminary study that local delivery with Centella asiatica and Punica
granatum extracts following scaling and root planing showed significant improvements in pocket depth and
attachment level compared to placebo. Punica granatum extract may provide a synergistic action in collagen
stabilization as tannins have the affinity for proteins, thus, forming bonds with collagen fibers.[22] In their follow-up
study, they observed there were significant improvement in the periodontal parameters and a decrease in the IL1 and IL-6 compared to baseline.[23]
Pomegranate components could promote oral health, including reducing the risk of gingivitis. Thrice daily mouth
rinsing with pomegranate extract dissolved in water increased the levels of antioxidant activity and decreased
activities of aspartate aminotransferase.[24] Aspartate aminotransferase is considered an effective indicator of cell
injury and is elevated among periodontitis patients.[25]
Protein levels in saliva are higher among periodontitis patients correlating with the plaque forming bacterial content.
Saliva samples showed a significant decrease in protein levels after rinsing with pomegranate mouthwash indicating
its antibacterial activity.[26]
Pomegranate flavonoids have shown antibacterial action in vitro against gingivitis causing microbes.[27]
Streptococcus sanguis (S. sanguis) was sensitive to pomegranate extract and the inhibitory action was similar to
chlorhexidine.[28] S. sanguis is known to be the initial colonizer in dental plaque formation.[4] The possible
reason for this antibacterial effect are the tannins which increase bacteriolysis, interfere with bacterial adherence
mechanisms onto the tooth surfaces.[28] In contrast, fruit bark extract of pomegranate showed better inhibition of
growth of S. sanguis, Streptococcus sobrinus and Lactobacillus casei when compared to chlorhexidine.[29] A
hydroalcoholic extract pomegranate mouthrinse decreased colony forming units of plaque forming bacteria by
84% against chlorhexidine (79% inhibition) among 60 healthy patients. Pomegranate extract also suppressed the
ability of plaque forming microorganisms to adhere to the surface of tooth. Pomegranate may be a possible
alternate for the prevention of formation and treatment of dental plaque.[30]
A 10% Punica granatum extract gel was not efficient in preventing dental plaque formation and gingivitis.[7]
Whereas, a pomegranate gel (5g of carboxymethyl cellulose in 100mL of pomegranate juice) showed excellent
anti-gingivitis effect and significant reduction in plaque scores when used as an adjunct to mechanical debridement.
[1]
A recent study proved that pomegranate mouthwash had antibacterial efficacy against Aggregatibacter
actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), which are the
most important periodontal pathogens.[21] Punica granatum has shown antimicrobial activity against Eikenella
corrodens, which is a secondary colonizer in the biofilm formation on the tooth surface significantly more than
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chlorhexidine.[31] Rinsing with 30 mL of pomegranate juice was effective in reducing colony forming units of
dental plaque forming organisms by 32%.[32] Pomegranate mouthwash used two times daily for fifteen days
resulted in more efficient reduction of gingival and bleeding on probing scores when compared to chlorhexidine.
[33] Pomegranate gel when used as an adjunct with mechanical debridement was efficient in treating gingivitis with
an improvement in the clinical and microbiological parameters.[1] Significant improvement was observed in
plaque, gingival and bleeding indices among 92 patients who were instructed to use a toothpaste, which contained
pomegranate along with various other herbs.[34] Pomegranate thereby could be an excellent adjunct to the
conventional periodontal therapy as an anti-plaque agent due to its antibacterial properties.
Deep periodontal pockets are said to be associated with Helicobacter pylori (H. pylori) infection.[35] Increased
levels of H. pylori has been detected from the oral cavities of patients with periodontitis.[36,37,38] Pomegranate
has demonstrated significant antibacterial activity against H. pylori.[39] Hence, pomegranate could be beneficial in
treating periodontitis.
Pomegranate extracts have been found to be effective against herpes virus.[16] Recently, it has been suggested
that herpes viruses could be a trigger for periodontal tissue destruction. Herpes viruses may initiate and accelerate
progression of periodontitis due to its potential to stimulate cytokine release from host cells, impair host defense
mechanisms, resulting in increased virulence of resident periodontopathic bacteria.[15] Hence, pomegranate with
its antiviral property could cure periodontitis as well. A recent study concluded that pomegranate peel extract had
a remarkable effect on Trichomonas tenax and could be used in the treatment of acute ulcerative gingivitis.[40]
Pomegranate extract is known for its wound healing properties. It is known to induce increased fibroblast
migration and proliferation, formation of collagen and angiogenesis.[41,42,43] 5%, 10% and 15% methanol peel
extract ointment of pomegranate resulted in a complete and faster wound healing.[41,44] The wound healing
properties can be attributed to the presence of tannins and polyphenols.[45]
Quorum sensing is the capacity of bacteria present in a biofilm to communicate with each other. Dental plaque is a
biofilm. Quorum sensing plays an important role in gene expression for development of antibiotic resistance,
promoting growth of bacteria essential for biofilm and discouraging growth of competitors.[46] Interfering with
quorum sensing signals could be a potential strategy for disease control.[47] Pomegranate extract inhibited quorum
sensing in Chromobacterium violaceum (C. violaceum) and Pseudomonas aeruginosa. This was
demonstrated by inhibition of violacein (purple pigment) production in C. violaceum and interference with
swarming in Pseudomonas aeruginosa. Pomegranate may be a rich source of compounds to overcome
pathogenic bacteria and development of antibiotic resistance.[48]
Pomegranate has positive effects on enteric probiotic bacteria.[47] It has shown enhanced growth of
Bifidobacterium species and Lactobacillus species.[49] These probiotic microorganisms are known to have
effect on periodontal pathogens by affecting their growth, adhesion and colonization.[50] They also decreased the
IL-1 and TNF- levels in the gingival crevicular fluid and interfered with the activity of tissue destructive enzymes
like elastase, myeloperoxidase and metalloproteinase-3.[51,52] Probiotic bacteria could be beneficial in treating
periodontitis by decreasing the periodontal pathogen burden in the oral biofilm and strengthening epithelial barrier
function, thus enhancing resistance to infections.[53]
Synergistic action was observed between methanolic pomegranate extract and antibiotics like chloramphenicol,
gentamicin, tetracycline, ampicillin and oxacillin against Methicillin resistant staphylococcus aureus (MRSA).[54]
The antibiotic activity of ciprofloxacin was enhanced by methanolic peel extract of pomegranate.[55] Pomegranate
because of its property of improving antibiotic sensitivity could be a promising adjunct in the treatment of
periodontitis.
Other uses of pomegranate in dentistry

A 10% topical pomegranate gel was efficient in reducing recurrent aphthous stomatitis pain and time for complete
healing of ulcers. This was attributed to its anti-inflammatory, antioxidant and antimicrobial properties of
pomegranate.[56] An 80% pomegranate peel extract lozenge was able to decrease gag reflex in soft palate up to
88.5% and in tonsils up to 92.5%. This effect could be due to the presence of tannins which have anesthetic
effects.[57] A gel based Punica granatum bark extract was effective in treating denture stomatitis as effectively
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as miconazole.[58]
Streptococcus mutans (S. mutans) is considered as the chief dental caries causing pathogen. S. mutans has
shown high sensitivity to pomegranate.[59] Pomegranate fruit extract gel was active against S. sanguis, S. mutans
and Streptococcus mitis (S. mitis) by controlling their adhesion on to glass surface and that it could be used to
prevent adherence of various microorganisms in the oral cavity.[60] In a recent in vitro study, pomegranate pulp
extract gel showed highly significant inhibitory effect at 5%, 25%, 50% and 100% against S. mutans when
compared to aloe vera and sorbitol. This action is probably due to the antimicrobial property of tannins.[61]
Pomegranate could be a potential anticariogenic agent due to its property to inhibit S. mutans.
Safety of pomegranate

Pomegranate and its constituents have been consumed for centuries without adverse effects.[8] Studies of
pomegranate constituents in animals at concentrations and levels commonly used in folk and traditional medicine
did not indicate any toxic effects.[13] Pomegranate juice, oil or powdered extracts can be consumed by healthy
individuals without high risk. No adverse effects on renal or liver function were observed in humans upon
administration of up to 1420 mg/day of pomegranate fruit extract tablets.[62]
P450 enzymes play a pivotal role in the metabolism of various drugs. Pomegranate inhibited this enzyme resulting
in altered drug pharmacokinetics of tolbutamide, carbamazepine and pentobarbital.[63,64,65] Future studies
should be directed with emphasis on bioavailability of compounds, effective and safe doses of pomegranate that
can be used in dentistry.
CONCLUSION
In the recent years, the use of plants with preventive and therapeutic effects contributing to health care has
increased. The reason probably for the growing interest in phytotherapy is development of microbial resistance to
antibiotics, consumers becoming aware of the adverse effects associated with traditional antibiotics and studies
proving that plants possess medicinal values. Pomegranate referred as the Nature's power fruit possesses a vast
ethno-medical history and represents a phytochemical reservoir of heuristic medicinal value. Known for its potent
antibacterial, antiviral, antioxidant, anti-inflammatory, wound healing, probiotic properties pomegranate could
prove truly as a Pharmacy unto itself for the treatment of periodontal disease underscoring the need for more
clinical research in this aspect.
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.

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