Pranay Jain et al. / Journal of Pharmacy Research 2009, 2(8),1223-1228 Review Article Available online through ISSN: 0974-6943 www.jpronline.info Strategies to prevent and treat dental caries and periodontal disease Pranay Jain*1 and Ram Kumar Pundir2 *1Lecturer in Biotechnology, University Institute of Engineering & Technology, University, Kurukshetra-136119 2Lecturer in Biotechnology, Kurukshetra Institute of Technology & Management, , Kurukshetra-136119 Received on: 07-04-2009; Accepted on: 15-06-2009

ABSTRACT

Dental caries and periodontal disease are closely associated with the development of dental plaque, formed as a result of the complex interactions between teeth and adsorbed host and bacterial molecules and the multiplication of associated microorganisms. The prevention and management of dental caries and periodontal disease historically has been the dominant focus of most dentists’ professional efforts. The review highlights the strategies to prevent and treat dental caries and periodontal disease and also highlights the use of natural products for the prevention of disease.

Keywords: Plaque, Dental caries, Periodontal disease, Antimicrobial agents, Natural products

INTRODUCTION Dental caries and periodontal disease are the most common oral dis- Dental caries can be traced back to be as old as civilization with its eases showing striking geographic variations, socio-economic pat- evidence seen even in skeletal remnants of preshistoric humans [8-9]. terns and severity of distribution all over the world. These diseases The prevalence of dental caries has greatly increased in modern times. pose challenges when it comes to determining their microbial etiol- The prevalence and distribution of dental caries is different in devel- ogy. Dental caries is a localized, progressive demineralization of the oped and developing countries. A decline in the level of dental caries hard tissues of the crown and root surfaces of teeth [1-3]. The dem- has been observed over the past four decades in developed coun- ineralization is caused by acids produced by bacteria, particularly tries [9-10]. This reduction has been attributed to the use of fluorides, Streptococcus mutans and lactobacilli that ferment dietary carbohy- change in lifestyles, improved oral hygiene practices, preventive dental drates. This occurs within a bacteria-laden gelatinous material called services and changes in diagnostic criteria [10-11]. The prevalence of dental plaque that adheres to tooth surfaces and becomes colonized caries is high in some developing countries and low in others, when by bacteria [4]. Thus, caries results from the interplay of three main compared to developed countries. , a developing country, has factors over time: dietary carbohydrates, cariogenic bacteria within shown an inclined trend of this disease over a relatively short period dental plaque, and susceptible hard tooth surfaces [5]. Among the of time [8]. The prevalence of dental caries in India is 80% with 5 three factors stated above, bacteria have been suggested to have the decayed teeth per child on an average at the age of 16 years [1]. It is strongest effect on the prevalence or incidence of dental caries [5]. a fact that oral hygiene is seen as a natural part of total body cleanli- Periodontal disease is a group of illnesses located in the gums and ness and that people desire fresh and healthy mouth with good smell- dental support structures (ligament and alveolar bone) and are pro- ing breath. Increased consumption of sugar has been stated as one of duced by certain bacteria encountered in subgingival plaque [6-7]. the causes for the increase in caries prevalence in developing coun- The American Association of Periodontics has classified periodontal tries [12]. disease into two categories: - gingivitis and periodontitis, according Epidemiological studies performed in many parts of the world and to the area of the gum involved. Gingivitis is very common and is among individuals with a widely varied background indicated that manifested clinically as the bleeding of the gingival or gum tissues destructive periodontal disease is nearly universal in children and without bone loss. Periodontitis occurs when the plaque induced adolescents [13]. The prevalence rate of periodontal disease in India inflammatory response in the tissue results in the actual loss of col- approach 90-100% [14-15]. lagen attachment of the tooth to the bone, and to loss of bone, which The pathogenicity of a microbe denotes its ability to cause disease. in some cases, can extend the entire length of the tooth root [7]. The indigenous flora usually protects against disease [13]. In the oral cavity, indigenous species become pathogenic when they leave mi- *Corresponding author. crohabitats where they are harmless (tongue papilla) to reproduce in Tel.: + 91-98133-70929 microhabitats (subgingival crevice) where their byproducts or pres- Telefax: +91-01744-239155 ence causes disease[3,16]. Indigenous species also become patho- E-mail: [email protected] genic when they reproduce under certain conditions in certain loca- tions, and becomes a larger proportion of the population [17]. Dental

Journal of Pharmacy Research Vol.2.Issue 7.August 2009 1223-1228 Pranay Jain et al. / Journal of Pharmacy Research 2009, 2(8),1223-1228 plaque is a complex permanent community, and the presence of large tion of periodontal disease is mainly based on plaque control [24]. number of indigenous species do not correlate with caries or peri- Although such approaches have been proven to be effective in con- odontal disease [16,18]. It is the balance among these species, the trolling these diseases, dental caries and periodontal disease still re- anatomical characteristics of the teeth and gingival crevices and the main a major public health problem in the general population with host diet and hygiene that, when upset, can lead to disease, referred substantial economic implications [19]. to as conditional diseases [11]. For dental caries, treatment is usually initiated when lesions are clini- The primary etiologic agents of dental caries are the streptococci, cally detectable (evidence of tooth substance loss, radiotranspirancy mainly Streptococcus mutans and S. sobrinus [12] (Table 1)S. mutans, in the tooth structure) and tissue damage is irreversible. Treatment a Gram-positive coccus, nonmotile facultative anaerobic microorgan- usually involves the removal of the affected tissues and placement of ism which can metabolize carbohydrates, is one of the most important a filling material. A similar approach is applicable to periodontal dis- oral bacteria which plays a major role in dental caries, bacteremia and ease [25-26]. Mechanical debridement is initiated when lesions (pres- consequently bacterial endocarditis among predisposed patients [19]. ence of periodontal pockets, loss of attachment, radiographic evi- Secondary infections are caused by the Lactobacillus spp., and acid dence of bone loss, bleeding) are observed. However, there are two tolerant streptococci such as Streptococcus sanguis (= sanguinis), shortcomings in this approach. First, clinicians lack diagnostic meth- S. gordanii and S. ovalis [16]. Yeast, such as Candida albicans, is ods to detect early tissue changes when lesions are still at a revers- also prevalent in the saliva and dental biofilm of caries active indi- ible change and can be treated in a noninvasive way. Secondly, as in viduals [11]. the case of dental caries, the filling approach is not necessarily syn- The most important and prevalent organisms found in the subgingi- onymous with control of the disease. Hence, the attention should be val area are anaerobic Gram-negative bacteria such as Aggregatibacter to emphasize prevention and treatment should be targeted at control- (=Actinobacillus) actinomycetemcomitans, Porphyromonas ling the etiological agents. Thus, oral microbiology plays a major role gingivalis, Prevotella intermedia and Tannerella (= Bacteroides) not only in the understanding of the etiology but also in preventing forsynthensis [20-21]. These bacteria play an important role in the and treating oral diseases [27-28]. onset and subsequent development of periodontitis, participating in In the present clinical scenario globally, there is a great interest in the the formation of periodontal pocket, connective tissue destruction, use of antimicrobial agents for prevention and treatment of plaque- and alveolar bone resorption by means of an immunopathogenic related oral diseases due to the spread of antibiotic resistance in oral mechanisms [22]. Organisms of probable periodontopathic signifi- cavity microorganisms [29-30]. There has been an extensive research cance include Campylobacter rectus, Peptostreptococcus micros, on the effectiveness of minimum inhibitory concentration of agents Dialister pneumosintes, Fusobacterium spp., Eubacterium spp., ß- for cariogenic and periodontopathogenic microorganisms [31]. Be- hemolytic streptococci, enterococci, pseudomonads and other en- cause dental caries is an infectious disease of bacterial origin, antimi- teric rods and yeasts such as Candida albicans, C. parapsilosis, crobial agents constitute a reasonable approach towards attenuating Saccharomyces cerevisiae [11]. Treponema denticola, Eubacterium not only the bacterial biofilm in situ, but also its transmission from saphenum, Porphyromonas endodontalis, T. forsynthensis, Filifactor host to host [19]. These approaches, while limited, based upon cer- alocis, Prevotella denticola, Cryptobacterium curtum, Treponema tain constraints inherent in the oral cavity, have their roots in early medium, T. socranskii, and Actinomyces naeslandii have also been attempts at plaque control and extend from mechanical approaches to discovered in periodontitis [22]. chemical approaches. However, a global reduction of plaque biofilm Although microbes are essential for the onset and progression of the mass may not lead to the desired effect of selectively eliminating or periodontal disease, they are probably not enough. This concept is reducing the caries associated microorganisms [16]. Thus, the aim of based on the fact that periodontal pathogens can occur in a person antimicrobial approach for the control of caries should be aimed not without clinical signs of the disease. In order for the disease to de- towards the elimination of all the plaque microorganisms but towards velop, a susceptible host is required [4]. The nature of susceptibility effecting an ecological shift from a cariogenic to non-cariogenic biofilm for destructive periodontal disease has long been an enigma. Today, [22]. While, in the case of periodontal disease, the mechanical peri- several factors have been linked to increased susceptibility and these odontal treatment alone is adequate to eliminate or resolve the clinical include age, poor oral hygiene, tobacco smoking, stress, systemic conditions in most cases, but adjunctive antimicrobial agents, deliv- diseases, decreased immunocompetence and genetic traits [22]. None ered either locally or systematically, can enhance the effect of therapy of these factors by themselves are probably capable to produce the in specific situations [33]. Since the organisms involved in caries and disease, but it seems likely that a set of risk factors is necessary to periodontal disease are in the form of biofilms which are less suscep- initiate the disease process. Exposure to lead and environmental to- tible to antimicrobial agents, therefore, there has been no effective bacco smoke, which has high concentrations of cadmium, has been antimicrobial agent yet searched, which can penetrate the biofilm [33]. linked with an increased risk of dental caries in children [23]. For this One of the primary mechanisms by which microbial homeostasis in reason, dental caries and periodontal disease are considered as a the mouth can be disrupted is by the repeated exposure of plaque to multifactorial diseases [22]. low pH following the frequent intake of fermentable dietary carbohy- Strategies for dental caries and periodontal disease preven- drates. This could be achieved by (a) inhibitors of acid production, tion and treatment (b) simple avoidance, between main meals, of food or drinks contain- Dental caries can be prevented by adequate oral hygiene, reduced ing fermentable sugars, (c) the consumption of items that contain frequency in sugar consumption and optimal use of fluoride. Preven- alternative sweeteners that are only weakly metabolized, if at all, by

Journal of Pharmacy Research Vol.2.Issue 8.August 2009 1223-1228 Pranay Jain et al. / Journal of Pharmacy Research 2009, 2(8),1223-1228 oral bacteria, or (d) stimulation of saliva flow after main meals [34]. helping control periodontal pathogens residing in various domains The use of fluoride increases the resistance of enamel to demineral- of the mouth from where they may translocate to periodontal sites. ization and to promote remineralization. Fluoride can also inhibit bac- Some of the antimicrobial agents being used in dental health prod- terial growth, but usually at concentrations much higher than those ucts contain broad-spectrum antimicrobial agents such as metronida- found in dental plaque. The anti-caries properties of fluoride, there- zole, amoxicillin and ciprofloxacin which can reduce plaque, espe- fore, have not generally been considered to involve its antimicrobial cially at sites that are difficult to clean. Care has to be taken with the activity. At sub-MIC levels, however, fluoride can reduce glycolysis, regular, unsupervised use of such agents, so that the natural ecology while its antibacterial and anti-metabolic properties are enhanced of dental plaque will not be disrupted. However studies have sug- markedly at low pH. Concentrations of fluoride that might be without gested that, at their concentrations in the mouth, the activity of some effect at neutral pH could be inhibitory during acid production and of these agents may be more selective than hitherto suspected. For thereby reduce the deleterious shifts in the plaque microflora by slow- example, in the same way that chlorhexidine can be used for selective ing the rate of change in pH [35]. suppression of mutans streptococci in plaque, so triclosan and zinc Antimicrobial agents, such as chlorhexidine, amoxicillin, penicillin and citrate, in combination, have been found to have greatest activity metronidazole can be used as an adjunct to mechanical cleaning for against periodontopathogens in vitro and in vivo, while leaving strep- plaque control. Such agents are generally selected on the basis of tococci associated with sound enamel and a healthy periodontium their spectrum of inhibitory activity, and on their bactericidal or bac- relatively unaffected [25]. teriostatic mode of action. However, agents delivered from dental Another approach has been to try to raise the redox potential (Eh) of products have a relatively short half-life in the mouth and may be the periodontal pocket (which is lowered during disease) to create an present for considerable periods at sub-MIC levels. At such concen- environment incompatible with the growth of obligate anaerobes. trations, they might still serve a valuable function by interfering with This has been tried with molecular oxygen or an oxygenating agent, bacterial metabolism, e.g., by inhibiting acid production [16]. with various rates of success. The use of redox dyes has been pro- Saliva is significant in a number of respects in terms of caries preven- posed which, while not releasing oxygen, can raise the redox poten- tion. Its flow is important in the clearance of fermentable sugars from tial of an ecosystem. Treatment with methylene blue leads to a sig- the mouth, while also providing buffering capacity to restore the pH nificant reduction in flow of GCF, and reduces the proportions of of plaque to resting values. Furthermore, saliva contains antimicro- obligate anaerobes and motile organisms in the subgingival microf- bial factors, as well as urea and peptides from which base can be lora accompanied by a concomitant increase in facultatively anaero- generated to raise the local pH; saliva can also remineralize enamel. bic and coccal bacteria. In vitro studies have also demonstrated that

Two approaches have been adopted to exploit these beneficial prop- methylene blue could raise the Eh of pre-reduced culture medium, and erties of saliva. First, the acid challenge to enamel, especially during significantly reduce the viable counts of a suspension of P. gingivalis between-meal periods, can be reduced by the consumption of snack [37]. foods, drinks, and confectionery that contain non-metabolizable sweet- The phenomenon by which one member of an ecosystem can inhibit eners (sugar substitutes). The sweetness of these agents stimulates the growth of another member is termed “bacterial interference”. The saliva flow in the absence of significant acid production, and this can possibility that antagonistic organisms could be used to control patho- promote remineralization of enamel. Some sugar substitutes-such as gens and prevent disease has been proposed for over 100 years and aspartame, saccharin, and xylitol, are also able to inhibit bacterial is termed “replacement therapy”. This approach has the potential growth, with saccharin and xylitol being particularly effective against advantage that it provides life-long protection with minimal cost or mutans streptococci. Second, saliva flow can be stimulated for ex- compliance on behalf of the recipient, once colonization by the “ef- tended periods after a meal-for example, by the chewing of gum sweet- fector” strain has been achieved. There are two main approaches by ened with sorbitol [27,36]. which replacement therapy is being considered as a means of en- Destructive periodontal disease is largely preventable, but is occa- hancing colonization resistance in plaque to prevent caries and peri- sionally stubborn and tenacious, requiring complex and frequent in- odontal disease, the pre-emptive colonization and competitive dis- tervention by the dental professional. Most conventional methods of placement [25,37]. treating disease involve mechanical removal of subgingival plaque In the pre-emptive colonization approach, ecological niches within and, sometimes, the use of antimicrobial agents, especially in ad- plaque are filled by a harmless or potentially beneficial organism vanced or refractory periodontal disease. Despite less being known before the undesirable strain has had an opportunity to colonize or about specific factors that result in changes in the subgingival micro- become established. The initial colonizer becomes integrated into flora, an alternative (ecological) approach would be to alter the envi- the oral ecosystem and subsequently excludes the pathogen [38]. ronment of the pocket to prevent the growth of the putative patho- Low-virulence mutants of mutans streptococci have been produced gens [37]. that are deficient in glucosyltransferase, intracellular polysaccha- Anti-inflammatory agents might break the cycle of tissue destruction ride, or lactate dehydrogenase (LDH) activity, and which are de- caused by both bacterial and host-derived proteases. This would signed to prevent subsequent colonization by “natural” mutans strep- also reduce the supply of gingival cervical fluid (GCF), and thereby tococci. However, wild-type revertants can occur, the degree of colo- restrict the availability of nutrients essential for the growth of some nization by the mutant can vary with the animal host, and mutants periodontopathogens. Systemic antibiotic therapy can be essential do not always compete successfully in vivo [37]. in eliminating pathogenic bacteria that invade gingival tissue and in In competitive displacement, a more competitive strain is introduced

Journal of Pharmacy Research Vol.2.Issue 7.August 2009 1223-1228 Pranay Jain et al. / Journal of Pharmacy Research 2009, 2(8),1223-1228 Table 1. Normal microflora of teeth and microorganisms associated with dental caries and periodontal disease [12].

Microorganisms Normal microflora Dental caries Periodontal disease Gram positive cocci Streptococcus mutans + + + Nonmutans streptococci S. sanguinis + + +/- S. mitis + + + Staphylococcus aureus - + + Peptostreptococcus sp. + + + Gram positive bacilli Lactobacilli (aerobic) + + - Lactobacilli (anaerobic) + + + Actinomyces naeslandii + + + A. viscosus + + + A. israeli - + + Gram negative cocci Viellonella sp. + + + Gram-negative bacilli Actinobacillus actinomycetemcomitans + - + Klebsiella sp. + + + Escherichia coli + - +/- Pseudomonas sp. + + +/- Prevotella melonenogenica - + + P. intermedia - + + Porphyromonasgingivalis - + + Fusobacterium spp. + + + Yeasts Candida albicans + + + C. dubliniensis + + + C. glabrata + + + C. parapsilosis + + + Saccharomyces cerevisiae + - +/- Protozoa Entamoeba gingivalis +‘ - + Trichomonas tenax - - + that would displace a pre-existing organism from plaque. Competi- lar amongst rural and uneducated people in India. For the treatment of tive displacement is of potentially greater clinical value, since it is periodontitis, massaging of gums with oils and ointments prepared not dependent on treatment with the “effector” strain at or before from herbs is still advised. It has been reported that some of the colonization by the undesired organism. An unusual strain of S. ayurvedic preparations have various ingredients which have analge- salivarius (TOYE-R) has been shown to displace S. mutans from the sic, anti-inflammatory properties as well as being able to facilitate teeth of rats and to inhibit tooth decay, but this organism was less cleansing and mouth freshening [38]. effective when attempts were made to implant it into human plaque There are an overwhelming number of studies on the antibacterial [37]. activities of plant and natural products derivatives. A few recent stud- Dental caries and periodontal disease have an infectious etiology ies have demonstrated antimicrobial activity against selected oral and immunization has been proposed as a means of controlling them. pathogens from natural sources. Sanguinaria (bloodroot) has been However, the approaches vary according to the nature of the bacteria found to inhibit the growth of 98% of bacterial isolates from human involved and the mechanisms of pathogenesis for these two very dental plaque [39]. Hanioka and coworkers [40] in a Japanese study different diseases. In the case of dental caries, proteins involved in (utilizing topically-applied CoQ10) found “significant improvements” colonization of teeth by Streptococcus mutans can produce antibod- in various measures of periodontal disease progression; these inves- ies that inhibit the cariogenic process. Periodontal vaccines are less tigators concluded that CoQ10 is a useful treatment for periodontal well developed, but some antigenic targets have been identified [26]. disease as a singular treatment or in combination with other nonsur- Among antibiotic alternatives are therapies derived from complemen- gical therapies. CoQ10 is found throughout the body and in higher tary and alternative medicine to cope with the wide-spread problem of amounts in heart, kidney, liver and pancreatic tissues. CoQ10 plays antibiotic resistance. A view to the past indicates that in ancient times, an important role in the production of adenosine triphosphate, or India was probably the most advanced country in dental health ser- ATP [40]. vices in the world. In the old ayurvedic literature of India, details of Several plants have been used historically for care of the teeth and gum diseases have been described and forms of treatment have also oral hygiene. In rural India, the mango is a commonly used in both been described. The practice of oral hygiene was included in daily urban and rural locations. Mango leaves are folded up and covered rituals. Ancient scriptures such as vedas and puranas proposed that with tea dust (finely ground, dried Camellia sinensis leaves) and the natural dentition could be preserved by appropriate periodontal rubbed against the teeth. One clinical investigation of this practice treatment. In the present times, ayurvedic treatment is still very popu- investigated the antimicrobial ability of mango leaves in oral hygiene.

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Mango leaves were shown to inhibit 2 types of bacteria (Prevotella organism in spite of its adverse effects. intermedia and Porphyromonas gingivalis) in greater proportion than Lippia sidoides (Verbenaceae), popularly known as “Alecrim those using a toothbrush [38]. pimenta” is a typical shrub commonly found in the Northeast of Bra- Several studies have been reported on the antibacterial effects of zil. Many plant species belonging to the genus Lippia yield very chewing sticks of neem (Azadirachta indica) and kikar (Acacia fragrant essential oils of potential economic value which are used by arabica) on cariogenic bacteria, such as S. mutans and on the industry for the commercial production of perfumes, creams, lo- periodontopathogens particularly Bacteriodes species and inhibitory tions, and deodorants. The antimicrobial activity of the oil and the action on dental plaque formation[41]. Melaleuca alternifolia (tea major components was tested against cariogenic bacterial species of tree oil) is well known for its antiseptic, bactericidal and antifungal the genus Streptococcus as well as C. albicans using the broth dilu- effects. A clinical trial using tea tree oil as an oral mouthwash ob- tion and disk diffusion assays. The essential oil and its major compo- served effectiveness at controlling oral bacteria and decreasing plaque nents thymol and carvacrol exhibited potent antimicrobial activity development during the time of the trial [42]. against the organisms tested with minimum inhibitory concentrations The miswak (Salvadora persica) mouthwash has been found to re- ranging from 0.625 to 10.0 mg/ml. The most sensitive microorganisms duce the levels of the cavity-causing bacterium mutans streptococci were C. albicans and S. mutans. The essential oil of L. sidoides and and improved indices of gingival health [43]. Joshi and coworkers its major components exerted promising antimicrobial effects against [44] carried out a study among school children of Kulasekharan vil- oral pathogens and is useful to combat oral microbial growth [49]. lage of Kanyakumari and found that the prevalence of dental caries Conclusion was low compared to the WHO recommended values. It was found to The key to a more complete understanding of the role of microorgan- be associated with the consumption of paddy husk powder for brush- isms in dental diseases such as caries may depend on a paradigm ing, which implicates that the paddy husk powder might be having shift away from concepts that have evolved from studies of classical the antiplaque properties. medical infections with a simple and specific (e.g. single species) Combination treatments with botanical medicines for oral health are etiology to an appreciation of ecological principles. The development quite common; ingredients are variable depending on practitioner of plaque-mediated disease at a site may be viewed as a breakdown of and patient variables. While the mixing of various botanicals for treat- the homeostatic mechanisms that normally maintain a beneficial rela- ment of oral conditions can be a highly successful approach, these tionship between the resident oral microflora and the host. When therapies are rarely evaluated on a larger scale, and for good reason assessing treatment options, an appreciation of the ecology of the as treatment utilizing herbal medicines are typically highly individual- oral cavity will enable the enlightened clinician to take a more holistic ized treatments. However, a combination of sage oil, peppermint oil, approach and consider the nutrition, physiology, host defenses, and menthol, chamomile, echinacea, myrrh, clove oil and caraway oil have general well-being of the patient, as these will affect the balance and been applied in a clinical trial with good results [45] . activity of the resident oral microflora. Future episodes of disease will From the native American plant Ceanothus americanus, ceanothic occur unless the cause of any breakdown in homeostasis is recog- acid and ceanothetric acid demonstrated growth inhibitory effects nized and remedied. As the putative dental caries and periodontal against S. mutans, Actinomyces viscosus and P. gingivalis [46]. pathogens are developing resistance against the commercially avail- Bakuchiol, isolated from the seeds of Psoralea corylifolia, a tree able antibiotics, the need of hour is to explore novel drugs that can be native in China showed antibacterial activity against S. mutans, Lac- used in the prevention and treatment of not only the dental infections tobacillus acidophilus and Actinomyces viscosus [47]. but also of other dreadful diseases for which there has been no opti- The antimicrobial activity of garlic crude extract against oral microbiota mal drug yet discovered. was evaluated in vitro and in vivo in two separate studies by Groppo References et al. [48]. The evaluation of antimicrobial activity was carried out in 1. Meghashyam B, Nagesh L, Ankola A. Dental caries status and treat- two phases. Study 1 consisted of the evaluation of minimum inhibi- ment needs of children of fisher folk communities, residing in the tory (MIC) and bactericidal (MBC) concentrations against nine strep- costal areas of Karnataka region, . West Indian Med. J., tococci strains. In study 2, a 2.5% garlic solution was used as a mouth- 2007, 56, 96-98. 2. Marsh PD. Are dental diseases examples of ecological catastrophes? wash in a 5-week study by 30 subjects. Blood agar and Mitis Salivarius Microbiology, 2003, 149, 279-294. Bacitracin agar were inoculated with patients’ saliva to quantify oral 3. Ruby J, Goldner M. Nature of symbiosis in oral disease. J. Dent. Res., microorganisms and mutans streptococci. Study 1 showed MIC from 2007,86, 8 - 11. 0.5 to 32.0 mg ml -1 for clone 2 and from 8 to 64.0 mg ml-1 for one extract. 4. Fujita K, Matsumoto-Nakano M, Inagaki S, Ooshima T. Biological functions of glucan-binding protein B of Streptococcus mutans. Oral MBC ranged from 1.0 to 128.0 mg ml-1and from 8.0 to 128.0 mg ml-1 Microbiol. Immunol., 2007,22, 289-292. regarding two extracts respectively. Study 2 showed that 2.5% garlic 5. Nishikawara F, Nomura Y, Imai S, Senda A, Hanada N. Evaluation of mouthwash solution had good antimicrobial activity against mutans cariogenic bacteria. Eur. J. Dentistry., 2007,1, 31-39. streptococci and oral microorganisms. Maintenance of reduced sali- 6. Smalley JW. Pathogenic mechanisms in periodontal disease. Adv. Dent. Res.,1994, 8, 320-328. vary levels of streptococci was observed after 2 weeks at the end of 7. Giannobile WV. Periodontal surveillance–Implications in the promo- mouthwash use. Unpleasant taste (100%), halitosis (90%) and nau- tion of public health. J. Periodontol., 2007,78, 1177. sea (30%) were reported by patients after the end of the study. It was 8. 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Journal of Pharmacy Research Vol.2.Issue 8.August 2009 1223-1228