Pomegranate juice ( Punica granatum ) as an ideal mouthrinse for fixed orthodontic patients

Background: Prevention of caries as well as periodontal disease is mandatory during orthodontic treatment. Nevertheless, the use of antiseptic mouthrinse is contraindicated for prolonged use. Pomegranate juice is a polyphenol-rich juice with high antioxidant capacity as well as antimicrobial properties. It has been shown to exert beneficial characteristics for orthodontic patients such as antioxidant and anti inflammatory effects. Moreover, it contained fluoride and phosphorous which are cariostatic. Previous study in fixed orthodontic patients revealed that rinsing with this juice showed reduced dental plaque and superior compared with chlorhexidine. If it has unwanted effect by reducing pro-inflammatory reaction that also needed in orthodontic movement is not clearly understood. Purpose: The aim of the present review was to discuss the beneficial and unwanted effect of pomegranate juice mouthrinse towards orthodontic treatment. reviews: Pomegranate has antimicrobial activity, its methanolic skin extract is the most potent followed by seed juice. Nevertheless, seed juice is not only tastier, easier to make but also has mild antimicrobial potency which is beneficial for long-term use. Healthy periodontal tissue is preferable for orthodontic movement since it resulted in less unwanted bone resorption. Conclusion: Regarding its beneficial effect and safety of pomegranate juice if use daily mouthrinse in fixed orthodontic patients, it could be proposed as an ideal long term use mouthrinse for fixed orthodontic patients. However, further researches should be done to verify this concept.


introduction
A frequent asked question: "Is it safe to use mouthrinse when you have braces?", it seems a simple question, nevertheless, to answer it many things should be considered.It is logical that wearing orthodontic appliances has been known to induce intraoral changes, such as increased plaque accumulation and elevated bacterial colonization along with potential enamel demineralization and a harmful effect on periodontal tissues such as gingivitis and periodontitis. 1,2ixed orthodontic appliances, such as orthodontic brackets, wires as well as elastomeric modules and chains etc., increase the number of retention places for dental plaque accumulation.All these factors make it even more difficult to maintain oral hygiene.Self-cleaning is also more difficult because of the reduced effect of mechanical chewing and rinsing the food residues off by saliva.Subsequent accumulation of plaque can causing to development of chronic periodontal inflammation and can progress to gingival enlargement.Gingival enlargement inhibits hygiene measures, slows down orthodontic tooth movement and cause aesthetic and functional problems. 2,3ven without brackets, for many people, especially children, it is difficult to adequately comply with recommended mechanical methods of plaque control and to achieve the necessary level of oral hygiene.Tooth brushing removes up to 50% of plaque biofilm, and is even more effective when used in combination with flossing. 2,4][3][4] Several requirements for long term use of oral rinse should be followed in orthodontic treatment such as minimal adverse effect towards the properties of brackets and wires 5 as well as elastomeric modules and chains. 6he force degradation of elastomeric chain was related to water absorption and chemicals, the amount of loss in dry is less than in wet environments and especially in biofresh mouthrinse more than the neutral saliva. 6The role of pH fluctuation towards elastomeric chain force degradation. 7Regarding the alcohol containing mouth rinse (ACM), several opinions suggested that long term use may cause xerostomia and oral cancer which were not proven by studies.However, in orthodontics view, the use ACM should be limited since a study by Larrabee et al., 8 revealed that ACM increase force degradation of elastomeric chain.
The concept of mouthrinse is not new; they have been used for thousands of years, as mouthrinse ingredients containing salt, alum, and vinegar have been associated with Chinese, Indian, and Greek and Roman cultures.Although some rinses were historically used to freshen breath, there is evidence that modern therapeutic rinses may improve health.Therapeutic rinses may control oral biofilm, and biofilm is said to cause 70% to 80% of all human infections. 9,10e use of plants for treating diseases is as old as the human civilization.There are many plants which have been in use as traditional medicine, so they are called as medicinal plants.The use of plants for curing diseases was inevitable as is already proven by seeing the problems associated with synthetic antibiotics.Peels of some plants such as Punica granatum (having antibacterial properties) which are generally treated as wastes are true antibiotics as they are available for no cost, have no side effects and the most important benefit is that antibiotic resistant pathogens will be easily killed by these new and natural antimicrobials because they will take at least a few decades to get mutated and resistant to them. 9omegranate juice as mouth rinse for fixed orthodontic patients is not a new idea.Pomegranate mouth rinse was very efective to reduce dental plaque compared to chlorhexidine and distilled water in fixed orthodontic patients. 11However, the adverse effect towards fixed orthodontics accesories (wires, elastomeric modules, coil springs) are still unclear.The aim of the present review is to discuss the beneficial and unwanted effect of pomegranate juice towards orthodontic treatment.

oral hygiene problem and maintenance in fixed orthodontic patients
Oral hygiene may be difficult to maintain during treatment, which may lead to plaque accumulation and gingival inflammation.It has been shown that orthodontic treatment induces changes in the oral environment, with an increase in the bacteria's concentration, and alterations in buffer capacity, pH acidity and salivary flow rate. 2,3owever, little is known about periodontal inflammation that results in diluted blood in saliva as well as the pH of dental plaque. 12Plaque accumulation and subsequent gingivitis are common in orthodontic patients because of the challenge of controlling oral hygiene with the combination of brackets, bands, wires as well as elastomeric modules and chains present. 2,3he main goal of an at-home oral hygiene for fixed orthodontic patients is toothbrushing with a fluoride containing toothpaste.The role of fluoride as an inhibitor of demineralisation becomes important and it has been shown that the presence of fluoride in solution at the time of acidic attack on the enamel may considerably slow down the rates of decay.It has been suggested that if preventive measures (fluoride supplementation and good oral hygiene) are followed and maintained throughout the course of orthodontic treatment, then the number of white spot lesions may be reduced. 12

Mouthrinse
Mouthrinses or mouthwashes are generally formulated using antibacterial agents (fluoride, alcohol, and cetylpyridinium chloride), flavours (thymol, eucalyptol, menthol, and mint oils), humectants (sorbitol, glycerol, propylene glycol) and colorants in an aqueous/ alcoholic medium.The sweetener (sodium saccharin) may be used to reduce/ eliminate the base taste of the product.Surfactants (sodium lauryl sulphate, cocoamidopropyl betaine) may also be used as foaming agents and water is the medium.Most of the currently available mouthwash products in the market contain alcohol.Though alcohol acts as an antiseptic and antibacterial, it induces dryness in the mouth and makes the environment more susceptible to the growth of bad breath producing bacteria.Hence, the recent trend in the market is to move from the alcohol-containing products to alcohol-free mouthrinses. 1,13enerally, some prescription of mouthrinse should be: (a) antimicrobial of oral pathogenic bacteria; (b) do not induce adverse effects (iritation, change taste buds perception, create oral flora imbalance, microbial resistance, decrease salivary fow and tooth or restoration staining); (c) contain fluorides. 1Nevertheless, for fixed orthodontic patients several requirements should be added that does not affect the properties of elastomeric modules and chains 14 as well as brackets and wires. 15In USA, mouthrinse should compared with ADA and/or FDA Guidelines, two antiseptic mouthrinses (and their generic equivalents) have been awarded the ADA Seal for chemotherapeutic control of supragingival plaque and gingivitis: 0.12% chlorhexidine gluconate (CHG) mouthrinse (Peridex ® ) and essential oils (EO) mouthrinse (Listerine ® ). 1 Some dental professionals may fear that antiseptic mouthrinses have a risk in killing or inhibiting normal flora with subsequent repopulation with opportunistic and/or more pathogenic or resistant organisms.The microbial shift would manifest as an overgrowth of opportunistic organisms, such as Candida.Fortunately, studies document no adverse effects on supragingival dental plaque microflora after 6 months of continued use with either CHG or EO.Evidence confirms that daily, long-term use (6 months or longer) of CHG or EO does not adversely affect oral microbial flora, including no microbial overgrowth, opportunistic infection, or development of microbial resistance. 1,16

Benefits of herbal antimicrobials
The widespread use of commercially available antimicrobials led to the consequence of emergence of antimicrobial resistant pathogens that ultimately led to the threat to global public health.Since 1980 the introduction of new antimicrobials has declined due to the huge expense of developing and testing new drugs.All commercially available antibiotics with prolonged use may have negative effect on human and animal health because they kill gut flora, so they needs to take probiotics to replace the killed gut flora.All the above points make a clear way for herbal antimicrobials. 14,15he use of plants for treating diseases is as old as the human civilization.There are many plants which have been in use as traditional medicine, so they are called as medicinal plants.The use of plants for curing diseases was inevitable as is already proven by seeing the problems associated with synthetic antibiotics. 15,17Peels of some plants as Punica granatum (having antibacterial properties) which are generally treated as wastes are true antibiotics as they are available for no cost, have no side effects and the most important benefit is that antibiotic resistant pathogens will be easily killed by these new and natural antimicrobials because they will take at least a few decades to get mutated and resistant to them. 17,18

Pomegranate
Pomegranate (Punica granatum L.) is native to the Mediterranean region and has been extensively used in the folk medicine of many countries.Pomegranate juice has potential anti-atherogenic effects in healthy humans and atherosclerotic effects in mice along with other nutritional and health advantages.As a result, pomegranate juice has become popular worldwide.Numerous studies on antioxidant activity have shown that pomegranate juice contains higher levels of antioxidants than most fruit juice. 14omegranate juice is an important source of anthocyanins (cyanidin, delphinidin, pelargonidin), which gives the fruit and aril its red color, and phenolics and tannins (punicalin, pedunculagin, punicalagin, ellagic acid). 18Pomegranate fruit contains many different kinds of polyphenolic antioxidants and commercial pomegranate juice has been shown to posses antioxidant activity three times higher than those of red wine and green tea (Table 1).The strongest antibacterial activity is the skin (rind, peel), followed by juice and the least is the seeds (red seeds are stronger than white).Other constituent of pomegranate juice which is beneficial to dental and periodontal health are calcium and phosphorus 15 as well as fluoride even only approximately 1/50th of green tea fluoride. 19Investigators had been noted that Pomegranate's active components, including polyphenolic flavonoids (e.g., punicalagins and ellagic acid) (Table 1), are believed to prevent gingivitis through a number of mechanisms including reduction of oxidative stress in the oral cavity, direct antioxidant activity; antiinflammatory effects; antibacterial activity; and direct removal of plaque from the teeth. 10hanged of salivary measures relevant to oral health including gingivitis after rinsing with Pomegranate extract. 20The changes were: (a) reduced total protein (which can correlate with plaque forming bacteria readings); (b) reduced activities of aspartate aminotransferase (an indicator of cell injury); (c) reduced alpha-glucosidase activity (a sucrose degrading enzyme); (d) increased activities of the antioxidant enzyme ceruloplasmin (which could give better protection against oral oxidant stress) and (e) increased radical scavenging capacity.A placebo of cornstarch in water did not affect these measures.Pomegranate juice anti-iinflammatory and anti-oxidant effect. 14he effect of the hydroalcoholic extract (HAE) from pomegranate fruits on dental plaque microorganisms. 11he results, expressed as the number of colony forming units per milliliter (CFU/mL), show that the HAE was very effective against dental plaque microorganisms, decreasing the CFU/ml by 84% after mouthrinse.While similar values were observed with chlorhexidine, used as standard and positive control (79% inhibition), only an 11% inhibition of CFU/ml was demonstrated in the distilled water group, negative control.Therefore, HAE had an antibacterial activity against selected microorganisms, and may be a possible substitute for the treatment of dental plaque bacteria.
Moreover, studies conducted by Bhandari et al., 10 and Bhadbade SJ et al., 21 indicate that the pomegranate mouth rinse has an antiplaque effect.It also states that pomegranate extract is succeeded against the Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia strains in vitro.
These investigators suggest that pomegranate mouth rinse should be explored as a long-term antiplaque rinse, with prophylactic benefits.Pomegranate extracts in especially fruit skin extract is highly effective on growth of Streptococcus mutans in comparison with other extracts and various concentrations of tooth pastes, this fact may reflect efficiency of antibacterial activity of plant extracts, and ability of bacteria to resist other antibacterial agents such as pastes and antibiotics. 22omegranate extract suppresses the ability of S. mutans, mitis and sanguis to adhere to the surface of the tooth. 23he trick is to inhibit a common species of Streptococcus, preventing it from producing chemicals that create favorable conditions for fungi and other microorganisms to grow.Inhibition of interbacterial adhesion or coaggregation which important in biofilm formation was verified. 24nvestigate the methanolic extract of Punica granatum peel (MEPGP) revealed its effective concentrations in mg/mL against microbes (Table 2). 17

Effect of mouthrinse properties towards fixed orthodontic appliances
There are several mouthrinse properties that may affect the characteristics of fixed orthodontics appliances and accesories for example: (a) fluoride; (b) alcohol; (c) pH (acidity).Decay of elastomeric chain force in natrium fluoride 0.5% mouthwash plus saliva will degraded more rapidly than saliva only in higher force, that was 300 gram (p=0.020). 2 Nevertheless, in low force the difference was insignificant.Meridol® mouthwash, which contains stannous fluoride, was the solution in which the nickel titanium (NiTi) wires coupled with the different brackets showed the highest corrosion risk, while in Elmex® mouthwash, which contains sodium fluoride, the CuNiTi wires presented the highest corrosion risk. 6uch corrosion has two consequences: deterioration in mechanical performance of the wire-bracket system, which would negatively affect the final aesthetic result, and the risk of local allergic reactions caused by released Ni ions.The results suggest that mouthwashes should be prescribed according to the orthodontic materials used.A new type of mouthwash for use during orthodontic therapy could be an interesting development in this field. 6egarding to the safety of long term use of alcohol mouthrinse for oral cancer, it was still inconclusive. 13dditionally, alcohol containing mouthwashes afford little or no advantage in terms of efficacy over the alcohol free competitors.Alcohol causes a statistically significant (p=0.04)increase in the amount of force decay seen in elastomeric chains exposed to alcohol and commercial mouth rinse containing alcohol compared to those exposed only to water. 8H of the mouthwash products are varying from 3.7 to 6.5.The mouthwashes containing ethyl alcohol in the range of 6-8% are having pH in the range of 6.0-6.5 whereas those containing alcohol higher than 20% are acidic in nature (pH below 4 also). 26There was chemical changes in pH and total ethanol of mouth rinse evaluated over time. 27herefore, it is recommend that mouthwash manufacturers routinely check the change of pH of the mouthwashes, and use preservatives that maintain desirable pH homeostasis in the products.
Elastomeric chain force degradation increase rapidly in neutral or alkaline pH, 7 thus acidic environment facilitate higher performance.Fruit juices including pomegranate (2.75-4.14)are acidic liquid. 28As the result it is considered beneficial to elastomeric chain properties.

discussion
Based on this review, the prime question: "Is it safe to use mouthwash when you have braces?",should be answered: "No problem".Until now the safety of alcoholcontaining mouthrinses has been called into question, since many proprietary mouthwashes contain alcohol (ethanol) and in some, the concentration of ethanol can be as high as 26% have fuelled the controversy. 13Studies which appear to establish a relationship between the use of these rinses and oral cancer, are significantly flawed or imperfect. 1,29igh risk predisposition (children, alcohol dependent persons, and persons with genetic deficiencies in acetaldehyde metabolism) should use alcohol-free mouthwashes for the maintenance of oral health. 30Apart from these considerations for the individual, the risk of alcohol-containing mouthwash for public health appears very low compared to other routes of exposure to alcohol and acetaldehyde.Nevertheless, in fixed orthodontic patients, especially in Indonesia with high humidity lead to accelerate elastomers degradation, slowing down the force degradation by using an alcohol-free mouthwash is advisable.
Pomegranate juice is considered as acidic (pH 2.75-4.1), 7it is beneficial for orthodontic movement by slowing down elastomeric degradation.Even acidic, it is considered as a save mouthrinse, since pH of other mouthwash products are varying from 3.7 to 6.5.The mouthwashes containing ethyl alcohol in the range of 6-8% are having pH in the range of 6.0-6.5 whereas those containing alcohol higher than 20% are acidic in nature (pH below 4 also). 26nother ingredients such as calcium and fluoride of pomegranate juice is beneficial for maintaining the integrity of tooth enamel. 15Fluoride content of pomegranate juice is not as high as other fluoride containing mouthrinse.Excess of fluoride content in daily mouthrinse is disadvantageous for brackets and CuNiti wires since the are more prone to corrosion. 6ther than its non-alcoholic contains, pomegranate as a phytoplants mouthrinse have been shown to be good alternatives to synthetic chemical antimicrobial agents and antibiotics because of the serious side effects, antimicrobial resistance and the emergence of previously uncommon infections that have been reported to be on the increase due to inappropriate or widespread overuse of antimicrobials.On the other hand, clinicians should remind the potential risk of urticaria, alteration in taste, increase of calculus staining of teeth and mucous membranes and more rarely, oral mucosa desquamation and parotid swelling before prescribing chlorhexidine mouth wash as an antimicrobial agent. 14,18xtracts of Punica granatum peel in different concentrations were effective against S. epidermidis, S. aureus, S. mutans, S. sanguinis and S. salivarius. 24,31ntibacterial activity may be related to the presence of hydrolysable tannins and polyphenolics in the pomegranate extract specifically punicalagin and gallagic acid. 32It means that the antimicrobial effect of tannins is related to its toxicity and molecular structure.Tannins may act on the cell wall and across the cell membrane because they can precipitate proteins.They may also suppress many enzymes such as gycosyltransferases.Therefore, tannic acid has the highest antibacterial effect against tested sensitive strains even at low concentrations.
Plaque may involve four or more different microorganisms combining forces to colonize the surface of the teeth.Remarkably, nature's own pomegranate fights the organisms' ability to adhere by interfering with production of the very chemicals the bacteria use as "glue" in bacterial adhesion or coaggregation. 24The use of pomegranate as anti-adhesion of microbes.Microbial adhesion is considered the first step in the sequence of events leading to colonization, is an important step leading to virulence and subsequent infection. 33ince every part of the pomegranate plants and fruit has its own active ingredients, therefore in producing a pomegranate mouthrinse one should refer to a reference such as in Table 1.Hence, the antibacterial activity of Punica granatum may be related to polyphenol structures because polyphenols may affect the bacterial cell wall, inhibit enzymes by oxidized agents, interact with proteins and disturb co-aggregation of microorganisms.Therefore, if our intention is to make mouthrinse with the phenolic compound, thus the peel and rind of pomegranate should be included.If only mild antimicrobial effect needed, just made it from white seed pomegranate. 16,19s an antioxidant, the effect of Pomegrante mouthrinse towards orthodontic tooth movement (OTM) is still unclear.A rat model of orthodontic tooth movement which consumed anti oxidants Resveratrol or N-acetylcysteine. 34t suppressed the expression of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in the periodontal ligament tissues compared to the vehicletreated group, thus inhibit bone resorption and retard OTM.Consumption of pomegranate extract accelerate bone formation. 35However, pomegranate consumption is different with mouthrinsing only, therefore the retardation of OTM should be minimal.
Based on the literatures it is concluded that pomegranate is an ideal mouthrinse for fixed orthodontic patients since it has abundant benefits for long term use.The beneficial properties are: (a) antimicrobial of oral pathogenic bacteria; (b) prevent the interbacterial adhesion (coaggregation) as well as bacteria to tooth adherence by interfering adhesive production; (c) do not induce adverse effects (iritation, change taste buds perception, create oral flora imbalance, microbial resistance, decrease salivary fow and tooth or restoration staining); (d) non-alcoholic; (e) as fruit juice it has acceptable taste; (f) do not accelerate elastomeric chain force degradation since it has acidic pH; (g) non corrosive for orthodontic brackets and CuNiti wires, cause of its mild fluoride content; (h) Others are its antiinflammatory and antioxidant effect as well as calcium and phosphorus contents which beneficial towards dental and periodontal health.However, further researches should be done for its antiinflammatory and antioxidant effect towards bone remodelling which mandatory in orthodontic movement.

table 2 .
17tibacterial and antifungal properties of methanolic extract of punica granatum at three different concentrations17measured by the diameter of zone of inhibition in mm, Conc= Concentration, **Ciprofloxacin and nystatin are the positive control group. *