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<front>
<journal-meta>
<journal-id journal-id-type="marcador">2312</journal-id>
<journal-title-group>
<journal-title specific-use="original" xml:lang="es">Universitas Odontológica</journal-title>
<abbrev-journal-title abbrev-type="publisher" xml:lang="es">Univ. Odontol.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="ppub">0120-4319</issn>
<issn pub-type="epub">2027-3444</issn>
<publisher>
<publisher-name>Pontificia Universidad Javeriana</publisher-name>
<publisher-loc>
<country>Colombia</country>
<email>revistascientificasjaveriana@gmail.com</email>
</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="art-access-id" specific-use="redalyc">231252657002</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Artículos</subject>
</subj-group>
</article-categories>
<title-group>
<article-title xml:lang="en">
<bold>Antibacterial Efficacy of Epigallocatechin -3 -  gallate  against  Streptococcus  mutans:  A Systematic Review</bold>
</article-title>
<trans-title-group>
<trans-title xml:lang="es">
<bold>Eficacia antibacteriana de la epigalocatequina-3-galato contra el Streptococcus mutans: Revisión sistemática 

 </bold>
</trans-title>
</trans-title-group>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name name-style="western">
<surname>Araújo Ferreira</surname>
<given-names>Danielly Cunha</given-names>
</name>
<xref ref-type="corresp" rid="corresp1"/>
<xref ref-type="aff" rid="aff1"/>
<email>danielly@usp.br</email>
</contrib>
<contrib contrib-type="author" corresp="no">
<name name-style="western">
<surname>Fernandes Polizeli</surname>
<given-names>Silvana Aparecida</given-names>
</name>
<xref ref-type="aff" rid="aff2"/>
</contrib>
<contrib contrib-type="author" corresp="no">
<name name-style="western">
<surname>Bezerra da Silva</surname>
<given-names>Léa Assed</given-names>
</name>
<xref ref-type="aff" rid="aff3"/>
</contrib>
<contrib contrib-type="author" corresp="no">
<name name-style="western">
<surname>Calvano Küchler</surname>
<given-names>Erika</given-names>
</name>
<xref ref-type="aff" rid="aff4"/>
</contrib>
<contrib contrib-type="author" corresp="no">
<name name-style="western">
<surname>de Rossi</surname>
<given-names>Andiara</given-names>
</name>
<xref ref-type="aff" rid="aff5"/>
</contrib>
</contrib-group>
<aff id="aff1">
<institution content-type="original">University of São Paulo,
Ribeirão Preto, São Paulo, Brazil</institution>
<institution content-type="orgname">University of São Paulo</institution>
<country country="BR">Brasil</country>
</aff>
<aff id="aff2">
<institution content-type="original">University of São Paulo,
Ribeirão Preto, São Paulo, Brazil</institution>
<institution content-type="orgname">University of São Paulo</institution>
<country country="BR">Brasil</country>
</aff>
<aff id="aff3">
<institution content-type="original">University of São Paulo,
Ribeirão Preto, São Paulo, Brazil</institution>
<institution content-type="orgname">University of São Paulo</institution>
<country country="BR">Brasil</country>
</aff>
<aff id="aff4">
<institution content-type="original">University of São Paulo,
Ribeirão Preto, São Paulo, Brazil</institution>
<institution content-type="orgname">University of São Paulo</institution>
<country country="BR">Brasil</country>
</aff>
<aff id="aff5">
<institution content-type="original">University of São Paulo,
Ribeirão Preto, São Paulo, Brazil</institution>
<institution content-type="orgname">University of São Paulo</institution>
<country country="BR">Brasil</country>
</aff>
<author-notes>
<corresp id="corresp1">
<email>danielly@usp.br</email>
</corresp>
</author-notes>
<pub-date pub-type="epub-ppub">
<season>January-June</season>
<year>2017</year>
</pub-date>
<volume>36</volume>
<issue>76</issue>
<history>
<date date-type="received" publication-format="dd/mm/yyyy">
<day>25</day>
<month>04</month>
<year>2016</year>
</date>
<date date-type="accepted" publication-format="dd/mm/yyyy">
<day>01</day>
<month>05</month>
<year>2017</year>
</date>
</history>
<permissions>
<ali:free_to_read/>
<license xlink:href="https://creativecommons.org/licenses/by/4.0/">
<ali:license_ref>https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.</license-p>
</license>
</permissions>
<abstract xml:lang="en">
<title>Abstract</title>
<p>
<bold>
<italic> Background:</italic>
</bold> Green tea, obtained from the <italic>Camellia sinensis</italic>, is one of the most popular drinks worldwide and has recently been in the focus of scientific research due to its beneficial effects on general health. Several studies suggest that, among the polyphenols found on green tea, epigallocatechin-3-gallate (EGCG) is the most bioactive compound and is responsible for its antibacterial activity. <bold>
<italic>Purpose:</italic>
</bold> To conduct a qualitative systematic review of literature evaluating the antibacterial efficacy of EGCG against <italic>Streptococcus mutans (S. mutans).</italic>
<bold>
<italic> Methods:</italic>
</bold> Relevant published studies included in the Pubmed (1966- June 2015), Scopus (1960- June 2015), Web of Science (1900- June 2015), and Google Scholar databases were identified. Publications of <italic>in vitro</italic> studies, which studied EGCG antibacterial efficacy against S. mutans, were extracted and pooled in a table. The evaluation included inhibition zone measures, reduction of the number of microorganisms, and biofilm formation. <bold>
<italic>Results:</italic>
</bold> Twelve studies were selected to compose this systematic review. Eleven of them showed that EGCG has antibacterial efficacy against S. mutans. <bold>
<italic>Conclusions</italic>
</bold>: <italic>In vitro</italic> evidence available confirms the antibacterial activity of EGCG against S. mutans.  </p>
</abstract>
<trans-abstract xml:lang="es">
<title>Resumen</title>
<p>
<bold>
<italic> Antecedentes:</italic>
</bold> El té verde, obtenido de la <italic>Camellia sinensis</italic>, es una de las bebidas más populares en el mundo y ha estado recientemente en el foco de atención de la investigación científica por sus efectos benéficos en la salud general. Varios estudios sugieren que, entre los polifenoles encontrados en el té verde, la epigalocatequina-3-galato (EGCG) es el compuesto más bioactivo y es el responsable de su actividad antimicrobiana. Objetivo: Realizar una revisión sistemática cualitativa de la literatura donde se evalúe la actividad antibacteriana de la EGCG contra el <italic>Streptococcus mutans (S. mutans)</italic>. <bold>
<italic>Métodos:</italic>
</bold> Se identificaron estudios relevantes incluidos en las bases de datos bibliográficas Pubmed (1966-junio del 2015), Scopus (1960-junio del 2015), Web of Science (1900- junio del 2015) y Google Académico. Los datos de estudios<italic> in vitro</italic> que investigaron la eficacia antibacterial de la EGCG contra el S. mutans se seleccionaron y organizaron en una tabla. La evaluación de los estudios incluyó los criterios: medidas de las zonas de inhibición, reducción del número de microorganismos y formación de biopelícula. <bold>
<italic>Resultados:</italic>
</bold> Se seleccionaron 12 estudios para la revisión sistemática. Once de ellos comprobaron la eficacia antibacteriana de la EGCG contra el S. mutans. <bold>
<italic>Conclusiones:</italic>
</bold> La evidencia <italic>in vitro</italic> disponible confirma que la EGCG tiene un efecto antibacteriano contra el S. mutans.  </p>
</trans-abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>antimicrobial
agents</kwd>
<kwd> Camellia sinensis</kwd>
<kwd> dental caries</kwd>
<kwd>
epigallocatechin-3-gallate</kwd>
</kwd-group>
<kwd-group xml:lang="es">
<title>Palabras clave</title>
<kwd>agentes
antimicrobianos</kwd>
<kwd> Camellia sinensis</kwd>
<kwd>
caries dental</kwd>
<kwd> epigalocatequina-3-galato</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="33"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>HOW TO CITE THIS ARTICLE</meta-name>
<meta-value>Ferreira
DCA, Polizeli SAF, da Silva LAB, Küchler EC, de Rossi A. Antibacterial Efficacy
of Epigallocatechin-3-gallate against <italic>Streptococcus
mutans</italic>: A Systematic Review. Univ
Odontol. 2017 Ene-Jun; 36(76). <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.11144/Javeriana.uo36-76.aees">https://doi.org/10.11144/Javeriana.uo36-76.aees</ext-link>
</meta-value>
</custom-meta>
<custom-meta>
<meta-name>THEMATIC FIELDS</meta-name>
<meta-value>cariology; catechins; microbiology</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>
<bold>INTRODUCTION</bold>
</title>
<p> The green tea, originating from the <italic>Camellia sinensis</italic> plant, is one of the most popular drinks and has received special attention by presenting known effects on general health [<xref ref-type="bibr" rid="231252657002_ref1">1</xref>,<xref ref-type="bibr" rid="231252657002_ref2">2</xref>]. Among the components of this tea, Epigallocatechin-3-gallate (EGCG) is the substance found in greater amounts, constitutes about 59% of total substances and the most bioactive component [<xref ref-type="bibr" rid="231252657002_ref3">3</xref>]. </p>
<p> In addition to these properties, can be highlight the antimicrobial action, several studies have reported the inhibitory effects of EGCG on both Gram-positive and Gram-negative bacteria, such as Enterococcus spp., S<italic>taphylococcus aureus, Streptococcus spp., Salmonella spp</italic>., and <italic>E. coli</italic> [<xref ref-type="bibr" rid="231252657002_ref1">1</xref>,<xref ref-type="bibr" rid="231252657002_ref2">2</xref>,<xref ref-type="bibr" rid="231252657002_ref4">4</xref>, <xref ref-type="bibr" rid="231252657002_ref5">5</xref>, <xref ref-type="bibr" rid="231252657002_ref6">6</xref>]. In Dentistry, this substance was proposed in toothpaste [<xref ref-type="bibr" rid="231252657002_ref7">7</xref>], because it presents a broad spectrum of action against <italic>Streptococcus mutans</italic> (<italic>S. mutans</italic>) and <italic>Streptococcus sobrinus</italic> (<italic>S. sobrinus</italic>). The action of catechin occurs preventing bacterial adhesion to the tooth surface by inhibiting glucosyltransferase enzyme and bacterial amylase [<xref ref-type="bibr" rid="231252657002_ref1">1</xref>,<xref ref-type="bibr" rid="231252657002_ref2">2</xref>,<xref ref-type="bibr" rid="231252657002_ref8">8</xref>].  </p>
<p> The primary role of <italic>S. mutans</italic> in the pathogenesis of dental caries resides with it is ability to assemble an insoluble polymeric matrix [<xref ref-type="bibr" rid="231252657002_ref9">9</xref>]. This microorganism is considered the main and predominant etiologic agent of dental caries and contributes significantly to the virulence of the biofilm, especially in the presence of sucrose [<xref ref-type="bibr" rid="231252657002_ref10">10</xref>]. There are many studies regarding the use of EGCG in medicine, however few and recent studies have been conducted on the use of EGCG in Dentistry, since this substance is found in a very popular drink that contacts the oral mucosa, it may have antimicrobial efficacy and play an anticariogenic role. The research question behind this systematic review was: Does EGCG have antibacterial efficacy against <italic>S. mutans</italic>? The hypothesis of this study was: EGCG performs an antibacterial efficacy against the microorganisms <italic>S. mutans</italic>. This systematic review evaluated the antibacterial efficacy of the EGCG against <italic>S. mutans</italic>.</p>
</sec>
<sec sec-type="methods">
<title>
<bold>METHODS</bold>
</title>
<p> Originals <italic>in vitro</italic> studies that investigated the EGCG as an antibacterial agent were included, as well as those who evaluated the antibacterial activity of this substance against <italic>S. mutans</italic>, which have been published in the English language. </p>
<p>
<italic> In vivo, ex vivo, in situ</italic>, animals, clinical studies, letters to the editor, case reports, case series, review and studies with explicit convenience sample (institutionalized/hospitalized individuals, vulnerable population, sample selection performed according to the researcher interest) were excluded, as well as patents, conferences, studies evaluating other extracts of green tea, other microorganisms and other studies that have been published in non-English language.  </p>
<p> Electronic searches were conducted to identify the published literature in the Pubmed Medline (1966- Feb 2016), SciVerse Scopus (1960- Feb 2016), Web of Science (1900- Feb 2016) and Google Scholar databases. The Google Scholar was used as a program aimed at the international literature.  </p>
<p> The search strategy was based on the following Medical Subject Heading terms (MeSH) and free terms: (“epigallocatechin-3-gallate” [MeSH] OR “EGCG” [MeSH] OR “<italic>Camellia sinensis</italic>” [MeSH] OR “green tea” [all]) AND (“<italic>Streptococcus mutans</italic>” [MeSH] OR “S. mutans” [all] OR “<italic>Mutans streptococci</italic>” [all]). Data was extracted and pooled in a table, to facilitate the visualization of information. </p>
<p> All papers were managed using the software EndNote X7 (Thomson Reuters, New York, NY, US). Duplicate papers were excluded. Titles and abstracts were screened independently by two reviewers based on the criteria mentioned above, (DCAF and SAFP). When there was some sort of disagreement, a third examiner was requested (ECK). After initial screening of titles and abstracts, full articles were evaluated by the same two reviewers. Structured data collection worksheets were employed for the assessment of each publication. </p>
</sec>
<sec sec-type="results">
<title>
<bold>RESULTS</bold>
</title>
<p> The <xref ref-type="fig" rid="gf2">Figure 1</xref> presents a flow diagram, describing the process of selection of the studies about antimicrobial activity of EGCG against <italic>S. mutans</italic>. In Pubmed Medline database 40 studies were found, in Scopus database 48 studies were found, in Web of Science 109 studies were found, and finally 340 studies were found in the Google Scholar database.  </p>
<p>
<fig id="gf2">
<label>
<bold>Figure 1.</bold>
</label>
<caption>
<title>Flow diagram showing the
process of selection of the studies 

about antimicrobial efficacy
of EGCG against <italic>S. mutans</italic>.</title>
</caption>
<alt-text>Figure 1. Flow diagram showing the
process of selection of the studies 

about antimicrobial efficacy
of EGCG against S. mutans.</alt-text>
<graphic orientation="portrait" position="anchor" xlink:href="231252657002_gf2.png"/>
</fig>
</p>
<p> Studies were compared across all database and the studies in duplicate were excluded (91 studies). The remaining studies were analyzed and those, which did not meet the inclusion criteria, were excluded (434 studies). At the end, 12 studies were included in the full-text analysis and all were selected for inclusion in the systematic review. <xref ref-type="table" rid="gt1">Table 1</xref>, <xref ref-type="table" rid="gt2">1a</xref> shows the characteristics of the selected studies. The results demonstrated that EGCG present a considerable efficacy against <italic>S. mutans</italic>, by using different methods to analyze the antibacterial activity against this microorganism. Of the 12 studies evaluated, 11 demonstrated that EGCG showed efficacy against the lineage of microorganisms in question. However, 2 of them presented low efficacy, verifying interference in the formation of the biofilm, without causing the total inhibition. Only 1 study showed that EGCG is not an effective agent against <italic>S. mutans</italic>.</p>
<p>
<table-wrap id="gt1">
<label>Table 1.</label>
<caption>
<title>Characteristics of the selected studies in regarding the method used for antimicrobial efficacy evaluation of EGCG on SM.</title>
</caption>
<alt-text>Table 1. Characteristics of the selected studies in regarding the method used for antimicrobial efficacy evaluation of EGCG on SM.</alt-text>
<graphic orientation="portrait" position="anchor" xlink:href="231252657002_gt2.png"/>
<table-wrap-foot>
<fn-group>
<fn fn-type="other" id="fn1">
<p>Note: Bold form indicates the EGCG superiority against the control. GIC means glass ionomer cement; SEM means scanning electron microscopy; CHX means chlorhexidine; SM means Streptococcus mutans.</p>
</fn>
</fn-group>
</table-wrap-foot>
</table-wrap>
</p>
<p>
<table-wrap id="gt2">
<label>Table 1 (Cont.)</label>
<caption>
<title>Characteristics of the selected studies in regarding the method used for antimicrobial efficacy evaluation of EGCG on SM.</title>
</caption>
<alt-text>Table 1 (Cont.) Characteristics of the selected studies in regarding the method used for antimicrobial efficacy evaluation of EGCG on SM.</alt-text>
<graphic orientation="portrait" position="anchor" xlink:href="231252657002_gt3.png"/>
<table-wrap-foot>
<fn-group>
<fn fn-type="other" id="fn2">
<p>Note: Bold form indicates the EGCG superiority against the control. GIC means glass ionomer cement; SEM means scanning electron microscopy; CHX means chlorhexidine; SM means Streptococcus mutans.</p>
</fn>
</fn-group>
</table-wrap-foot>
</table-wrap>
</p>
</sec>
<sec sec-type="discussion">
<title>
<bold>DISCUSSION</bold>
</title>
<p> Dental caries is the most common oral disease and is an irreversible infectious disease of multifactorial origin, which leads to the destruction of dental hard tissue [<xref ref-type="bibr" rid="231252657002_ref10">10</xref>]. The biofilm plays an important role in the cause of tooth decay, the cariogenic microorganisms such as <italic>Streptococcus mutans, Streptococcus sanguis, Streptococcus salivarius, Streptococcus mitis, Streptococcus oralis</italic> and <italic>Lactobacillus acidophilus</italic> play a vital role in the etiology of the dental caries [<xref ref-type="bibr" rid="231252657002_ref11">11</xref>]. <italic>Streptococcus mutans</italic> is the major causative agent of dental caries and plays an important role in cariogenic biofilm formation [<xref ref-type="bibr" rid="231252657002_ref12">12</xref>,<xref ref-type="bibr" rid="231252657002_ref13">13</xref>]. It has been demonstrated that <italic>S. mutans</italic> are the primary etiological agent of caries [<xref ref-type="bibr" rid="231252657002_ref12">12</xref>].  </p>
<p> Medicinal plants have been used for therapeutic purposes for thousands of years and although their use has been popularly propagated between generations or described in pharmacopoeias, it has also aroused the interest of the current scientific community. Teas generally are rich in biologically active compounds such as flavonoids, catechins, polyphenols, alkaloids, vitamins and minerals that may contribute to the prevention and treatment of various diseases [<xref ref-type="bibr" rid="231252657002_ref14">14</xref>].  </p>
<p> It is important to emphasize that this systematic review has shown that although the methods used in the included studies are different, the results clearly support the important role of EGCG as an antibacterial agent against <italic>S. mutans</italic>. The EGCG agent inhibits the formation of biofilm and prevents infections [<xref ref-type="bibr" rid="231252657002_ref15">15</xref>], it is effective in inhibiting the formation of fermentable carbohydrates involved in the caries formation, which explains it is antimicrobial role [<xref ref-type="bibr" rid="231252657002_ref16">16</xref>]. Per the findings of this review, 11 studies showed favorable results for EGCG as an effective antibacterial agent against <italic>S. mutans</italic> in <italic>in vitro</italic> studies, acting both inhibiting the growth of the microorganism, as in the biofilm formation and in decreased acids production. Only one study found a negative result regarding the use of EGCG in the decontamination of infected dentin. This lack of effectiveness was justified in the study by the authors for perhaps be some interaction between EGCG with specific sites in collagen molecular structure [<xref ref-type="bibr" rid="231252657002_ref17">17</xref>].  </p>
<p> Several antimicrobial agents have been suggested, but the agent considered the gold standard is chlorhexidine gluconate (CHX). CHX widely used antimicrobial in Dentistry [<xref ref-type="bibr" rid="231252657002_ref18">18</xref>], due to it is strong antibacterial activity and ability to reduce the accumulation of oral biofilms [<xref ref-type="bibr" rid="231252657002_ref19">19</xref>]. Its efficacy can be attributed to bactericidal and substantivity effects [<xref ref-type="bibr" rid="231252657002_ref20">20</xref>], broad spectrum against microorganism, both aerobic and anaerobic, and selectively suppress the growth of caries-associated <italic>S. mutans</italic> [<xref ref-type="bibr" rid="231252657002_ref21">21</xref>]. CHX presents antimicrobial efficacy <italic>in vitro</italic> and <italic>in vivo</italic> (mouthwash) against salivary microbiota cariogenic and has a role in preventing the development of gingivitis [22]. Some studies compared EGCG with CHX [<xref ref-type="bibr" rid="231252657002_ref17">17</xref>, <xref ref-type="bibr" rid="231252657002_ref23">23</xref>, <xref ref-type="bibr" rid="231252657002_ref24">24</xref>, <xref ref-type="bibr" rid="231252657002_ref25">25</xref>, <xref ref-type="bibr" rid="231252657002_ref26">26</xref>]. The results of the comparison between CHX and EGCG showed that both substances were effective in inhibiting microbial the growth and biofilm formation. Other studies [<xref ref-type="bibr" rid="231252657002_ref26">26</xref>, <xref ref-type="bibr" rid="231252657002_ref27">27</xref>, <xref ref-type="bibr" rid="231252657002_ref28">28</xref>, <xref ref-type="bibr" rid="231252657002_ref29">29</xref>, <xref ref-type="bibr" rid="231252657002_ref30">30</xref>, <xref ref-type="bibr" rid="231252657002_ref31">31</xref>] used as negative control the absence of EGCG and in these situations; it was observed that there was a marked growth of microorganisms compared to the experimental group. One study compared the antimicrobial activity of EGCG whit black, oolong and Pu-erh tea against growth of <italic>S. mutans</italic> [<xref ref-type="bibr" rid="231252657002_ref32">32</xref>] and another study had no control group [<xref ref-type="bibr" rid="231252657002_ref33">33</xref>]. </p>
<p> Different methods have been used to evaluate the efficacy of EGCG against microorganisms, such as inhibition zone measurement, counting colonies forming units, counting of microorganisms and biofilm formation. In addition, different forms of manipulation of the EGCG, in some studies the solution was used [<xref ref-type="bibr" rid="231252657002_ref29">29</xref>, <xref ref-type="bibr" rid="231252657002_ref30">30</xref>, <xref ref-type="bibr" rid="231252657002_ref31">31</xref>], others incorporated into dental materials [<xref ref-type="bibr" rid="231252657002_ref24">24</xref>,<xref ref-type="bibr" rid="231252657002_ref27">27</xref>,<xref ref-type="bibr" rid="231252657002_ref28">28</xref>], and even as specific formula [<xref ref-type="bibr" rid="231252657002_ref26">26</xref>]. Despite all these variety in the method and material handling, the results suggested that it is a stable substance and with antimicrobial properties and able to inactivate the <italic>S. mutans</italic>, and thus inhibit the formation of biofilm. This systematic review demonstrates a clear efficacy of EGCG against <italic>S. mutans</italic> in <italic>in vitro</italic> studies.  However, clinical studies are needed to determine this substance as a potential agent for the prevention of dental caries.</p>
</sec>
</body>
<back>
<ref-list>
<title>
<bold>REFERENCES</bold>
</title>
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