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REVIEW ARTICLE
Year : 2016  |  Volume : 2  |  Issue : 2  |  Page : 38-41

Cranberry polyphenols: Beneficial effects for prevention of periodontal disease and dental caries


1 Department of Periodontology, Gian Sagar Dental College and Hospital, Rajpura, Punja, India
2 Department of Oral Implantology, Gian Sagar Dental College and Hospital, Rajpura, Punja, India
3 Clove Dental Clinic, Chandigarh, India

Date of Web Publication15-Mar-2017

Correspondence Address:
Sanjeet Gill
Department of Periodontology, Gian Sagar Dental College and Hospital, Banur, Rajpura, Punjab
India
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DOI: 10.4103/2454-3160.202222

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  Abstract 

Oral diseases are the major health problems with dental caries and periodontal disease among the most important preventable global infectious disease. More than 700 bacterial species or phenotypes, of which 50% have not been cultivated, have been detected in the oral cavity. Dental biofilm is associated with the initiation and progression of tooth decay and periodontal diseases. The conventional medical response to bacterial infections, administration of broad-spectrum antibiotics, has become less effective against emerging pathogens due to the evolution of drug resistance stemming in part from the antibiotic abuse. Therefore, there is a need to develop novel, narrow spectrum, therapeutics capable of maintaining the protective benefits of the normal microflora during treatment. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used as traditional medicines are considered as good alternatives. In this review, cranberry (Vaccinium macrocarpon) is the native North American fruit that has recently come into limelight owing to its numerous beneficial effects on dental caries, and periodontal health has been reviewed.

Keywords: Cranberry polyphenol, dental caries, periodontal disease


How to cite this article:
Gill S, Kaur A, Kapoor D, Goyal J, Duhan H. Cranberry polyphenols: Beneficial effects for prevention of periodontal disease and dental caries. Saint Int Dent J 2016;2:38-41

How to cite this URL:
Gill S, Kaur A, Kapoor D, Goyal J, Duhan H. Cranberry polyphenols: Beneficial effects for prevention of periodontal disease and dental caries. Saint Int Dent J [serial online] 2016 [cited 2017 Oct 24];2:38-41. Available from: http://www.sidj.org/text.asp?2016/2/2/38/202222



The oral microbial consortium is the most characterized polymicrobial community associated with the human host. The oral cavity comprises many surfaces, coated with a plethora of bacteria, the proverbial bacterial biofilm. Some of these bacteria have been implicated in oral diseases such as caries and periodontitis, which are among the most common bacterial infections in humans.[1] Other diseases such as oral and pharyngeal infections and oral tissue lesions are also significant health concerns.[2] Pathogenic microorganisms have been a constant source of human suffering.[3] Current methods of combating disease associated bacteria are mostly broad-spectrum antimicrobials such as chlorhexidine which acts by reducing viability of all bacteria in oral cavity, but there are many undesirable aspects to such bactericidal approach. Antibiotics that alter oral microbiota can put selective pressure on microorganisms to become resistant to drugs, kill symbiotic bacteria, and allow proliferation of other disease causing pathogens. The global need for alternative prevention and treatment options and products for oral diseases that are safe, effective, and economical comes from the rise in disease incidents (particularly in developing countries), increased resistance by pathogenic bacteria to currently used antibiotics, chemotherapeutic, opportunistic infections in immunocompromised individuals, and financial considerations in developing countries. Hence, the search for alternative products continues and natural phytochemicals isolated from plants used in traditional medicine are considered as good alternative to synthetic chemicals.[2] In this article, potential effects of American cranberry and its phytochemicals on virulence factors involved in biofilm formation and caries progression have been discussed.Cranberry (Vaccinium macrocarpon) is the North American fruit that has recently come into limelight owing to its numerous beneficial effects on health.[4] It is the fruit of a shrub of peat bogs located in the colder regions of North America belonging to Ericaceae family.[5] Cranberry itself is a unique, rich source of several classes of bioactive flavonoids including flavonols, anthocyanins, and proanthocyanidins (PACs) (Type A), which confer it the significant therapeutic potential.[4] Indeed due to its richness in polyphenols of high-molecular-weight, this berry has a demonstrable ability to inhibit adhesion of bacteria responsible for urinary disorders (such as  Escherichia More Details coli), gastric ulcer (such as Helicobacter pylori), or involved in the formation of dental caries or cavities and chronic periodontitis (such as Streptococcus mutans, Streptococcus gordonii, or Porphyromonas gingivalis).[5] A number of studies have suggested that cranberry polyphenols may promote oral health by inhibiting dental biofilm formation, acid production by S. mutans, and periodontopathogen-derived proteolytic enzymes and host inflammatory responses.[6] In addition to their impact on certain infectious agents, polyphenolic fractions prepared from Cranberries have been shown to inhibit proliferation of cancerous cells in the mouth, colon, and prostrate.[7] However, its antifungal interest has been poorly documented until now.[5]


  Cranberry and Its Effects on Periodontal Bacteria and Host Mechanism Top


Periodontitis is an inflammatory disorder leading to the destruction of tooth supporting tissues including the periodontal ligament and the alveolar bone, and it is caused by a specific group of Gram-negative anaerobic bacteria.[8] Two major factors contribute to the pathogenesis of periodontitis. First, periodontopathogens cause direct damage to periodontal tissue through the secretion of toxic products. Second, the host responses to periodontopathogens, which results in release of inflammatory mediators (pro-inflammatory cytokines, matrix metalloproteinases [MMP], and prostanoids) are also involved in the progression of periodontitis.[9] Specific bacterial species and bacterial complexes occur more frequently in diseased sites, while others are associated with healthy or stable periodontal tissues. Among the suspected periodontopathogens, the red complex, which includes P. gingivalis, Tannerella forsythia, and Treponema denticola, is strongly related to clinical measures of periodontitis, particularly pocket depth and bleeding on probing. These three major periodontopathogens produce a broad array of virulence factors such as proteolytic enzymes that allow them to colonize subgingival sites, resist host defenses, and cause tissue destruction.[9]

Current methods of combating periodontal infections are mostly broad-spectrum antibacterials. They act by reducing viability of all bacteria in the oral cavity, resulting in a decreased incidence of disease. There are many undesirable aspects of these antibacterial agents. To overcome these side effects, there has been a rising interest in naturally derived biologically active compounds that may have potential therapeutic uses in medicine and dentistry.

The formation of dental biofilm on teeth is the primary step leading to oral disease. Numerous drugs and drug delivery systems have been tested for their effect on dental biofilm formation and maturation.[10] Cranberry juice has been used in herbal medicine as an anti-infection agent. The nondialysable material (NDM) constituents of juice exhibit anticoaggregation activity against a variety of oral bacteria.[11] It has been shown that a high-molecular-weight fraction prepared from cranberry juice concentrate could inhibit lipopolysaccharide-induced pro-inflammatory cytokine and chemokine production by human macrophages.[12] Although chronic periodontitis is a multifactorial disease, the members of red complex, P. gingivalis, T. denticola, and T. forsythia are the three major etiological agents of chronic periodontitis. Gingipains, which can be both cell bound and secreted, are the main endopeptidases produced by P. gingivalis and contribute to the virulence properties of this bacterium since they degrade a large variety of host proteins.[13],[14] It was shown that the cranberry NDM fraction efficiently inhibits both Arg- and Lys-gingipain activities of P. gingivalis and significantly reduced destruction by periodontal diseases. T. denticola chymotrypsin-like activity has been shown to degrade transferrin, fibrinogen, gelatin, immunoglobulins, alpha-1 antitrypsin, and various basement membrane proteins and this activity was seen to be strongly inhibited by NDM fraction of cranberry. It has also been found that NDM fraction of cranberry by inhibiting both the collagenolytic and dipeptidyl peptidase IV activities of P. gingivalis can reduce Type I collagen (predominant protein accounting for about 60% of periodontal tissue volume) disruption and subsequent connective tissue fragilization in periodontitis patients.[9]

Labreque in 2006 and Yamanaka in 2008 revealed that the NDM (nondialyzable fraction/material) fraction of cranberry hindered the colonization by P. gingivalis and Fusobacterium nucleatum in the gingival crevice. Besides, it also prevented the adhesion of P. gingivalis to various proteins including Type I collagen thus reducing bacterial coaggregation in periodontal diseases.[4] A-type cranberry-PACs (AC-PACs) inhibited collagen degradation by P. gingivalis in a dose-dependent manner, suggesting that it may contribute to reducing the destructive process. AC-PACs have the ability to inhibit the activity of recombinant human MMP-1 and MMP-9 and the secretion of various MMPs by macrophages. It was also seen that AC-PACs significantly decreased the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5). IL-8 is an important chemoattractant that enhances the recruitment and infiltration of neutrophils to the sites of inflammation, while CCL5 has a significant chemotactic activity for basophils, eosinophils, monocytes, and T-helper Type I cells. Inhibition of secretion of IL-8 and CCL5 in human oral epithelial cells by AC-PACs stimulated by P. gingivalis suggests that they have the potential to reduce the influx of inflammatory cells to the diseased sites and the amplification of P. gingivalis induced inflammatory processes.[6]

The effect of AC-PACs on osteoclast formation and bone resorption activity was also seen. AC-PACs up to100 µg/ml were reported to be nontoxic for osteoclast cells. Tartrate-resistant acid phosphatase staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/ml caused a 95% inhibition of receptor activator of nuclear factor kappa B ligand (RANKL)-dependent osteoclast differentiation and increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP2 and MMP9. This study suggested that AC-PACs could interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption.[4]

It has also been seen that cranberry components might inhibit the nuclear factor-κB (activator of many cytokines and inflammatory processes) and MMP-3 thus regulating aggressive periodontitis' fibroblast inflammatory responses. AC-PACs also deflect the secretion of IL-8 and CCL5.[15]


  Cranberry and Its Effect on Dental Caries Top


Oral diseases induced by dental plaque continue to affect the majority of world population. Among them, dental caries is the single most prevalent and costly oral infectious disease.[16] This ubiquitous disease results from the interaction of specific bacteria and constituents of the diet within plaque (a natural biofilm) formed on the tooth surface. S. mutans is a key contributor to the formation of cariogenic plaque because this bacterium (i) effectively utilizes dietary sucrose to synthesize a large amount of extracellular polysaccharides (EPS), (ii) adheres tenaciously to glucan-coated surfaces, and (iii) is highly acidogenic and acid tolerant.[16] Polysaccharides, mostly glucans synthesized by microbial glucosyltransferases (GTF), are complex in structure, which changes over time during the extracellular matrix development.[16] For many oral streptococci, glucans comprise an extracellular slime layer produced in the presence of sucrose that promotes adhesion and formation of dental plaque biofilm.[17] The GTF decreased by S. mutans (particularly GTF B and GTF C) bind avidly to the pellicle formed on the tooth surface and to surface of other oral microorganisms which are highly active in the absorbed state.[16] The glucan synthesized by surface absorbed GTF B and GTF C provides specific binding site for bacterial colonization on the tooth surface and to each other (Schilling and Bowen, 1992), thus contributing to the initial steps of cariogenic plaque development in vivo.[16] If dental plaque is allowed to remain on tooth surfaces and is exposed to dietary carbohydrates frequently (especially sucrose), S. mutans as a member of the plaque community will continue to synthesize polysaccharides and metabolize sugar to organic acids. The elevated amount of EPS increases the biofilm stability and structural integrity and provides protection to the bacteria from inimical influences of antimicrobial and other environmental assaults.[18],[19] The low pH environment within plaque's matrix results in the dissolution of enamel, thus initiating the dental caries process. Therefore, EPS and acidification of biofilm's matrix are critical for formation and establishment of dental plaque.

Cranberry fruit (V. macrocarpon) has well-known antiadhesive properties and holds great potential as an antiadhesive agent against cariogenic mutans streptococci.[20] It causes disruption of acidogenic/aciduric properties of planktonic and biofilm cells of S. mutants. It has inhibitory effects on GTF activity and adherence by S. mutans and causes reduction of the formation of S. mutans biofilms and EPS content.[21] Quercetin-3-arabinofuranoside, myricetin, and procyanidin A2 found in cranberry have been found to inhibit GTF activity.[22] In a study, it was proposed that three putative pathways by which flavonols and PACs affect the virulence of S. mutans are (1) inhibition of insoluble glucans synthesis by surface-adsorbed GTF B and C, (2) inhibition of the proton-translocating F-adenosine triphosphate synthases (F-ATPases) activity, and (3) disrupting acid production.

In a study done by Yamanaka et al., they treated S. mutans and Streptococcus sobrinus cells with cranberry juice and found that it reduced cell surface hydrophobicity of the cells interfering with adhesion and the initial stages of biofilm formation. The authors hypothesized that cranberry juice components may interact with hydrophobic protein on the surface of the bacterial cell.[23]

Further, Steinberg et al. used high-molecular-weight, NDM constituents of cranberry juice to study its effects on S. mutans GTF activity and found NDM significantly reduced the GTF activity as well as fructosyltransferase, both solution and immobilized in saliva-coated hydroxyapatite. In addition to cell surface hydrophobicity and ability to synthesize glucan using GTFs, mutans streptococci are also acidogenic and aciduric. High metabolic activity creates an acidic environment, but bacterium is able to maintain an alkaline intracellular pH by removing protons through the use of an F-ATPase proton pump.[10] More importantly, flavonols and PACs were shown to interfere with the bacteria F-ATPase activity, preventing pH drop and subsequent acidification of extracellular environment.[20]

In another study, the influence of cranberry PACs on formation of biofilms by S. mutans on saliva-coated apatitic surface and on dental caries development in vivo demonstrated that a highly purified A-type proanthocyanadins (PAC) fraction reduced the formation of biofilms by S. mutans on saliva-coated apatitic surface, which correlated well with the reduction in the amounts of insoluble polysaccharides in the extracellular matrix. Topical application (60-s exposure, twice daily) with PACs (1.5 mg/ml) during biofilm formation resulted in less biomass and fewer insoluble polysaccharides than the biofilm treated with vehicle control (10% ethanol, v/v; P < 0.05). A-type PAC is uniquely found in high concentrations in cranberry and has shown to be biologically active.[16] Despite the lack of significant antibacterial (biocidal) activity, PAC treatments diminished the acidogenicity of S. mutans within biofilm by disrupting the overall bacterial metabolism. The lowest molecular weight compound tested was the PACs monomer catechin. Catechin was the only test agent that was not an effective inhibitor of GTF. All other PACs were able to inhibit GTF; PACs that had a degree of polymerization between 4 and 12 were the most potent inhibitors.[16]

Further, Weiss et al. investigated the effects on oral health of a mouthwash supplemented with the NDM fraction of cranberries. After 6 weeks of daily use of the mouthwash, total microflora notably S. mutans was significantly reduced. In support of these in vivo results, in vitro studies showed the NDM fraction inhibited the adhesion of S. sobrinus to a hydroxyapatite surface pretreated with saliva.[7]


  Conclusion Top


Cranberry seems to be the “wonder drug” for many dental problems. Newer techniques need to be developed to incorporate the concentrated polyphenolic fraction in toothpaste, mouth rinses, and other oral hygiene products. Local drug delivery or impregnation in resorbable fibers which could be packed in the gingival sulcus may benefit the patient to some extent by preventing the destruction of host tissues due to inhibition of MMPs and other anti-inflammatory molecules. Cranberry and its constituents exhibit interesting properties for oral health and thus appear promising for the development of new therapeutic approaches for adjunctive treatment of oral diseases.

There are no conflicts of interest.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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