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Therapeutic applications and antibacterial and antifungal activities of Syzygium cumini (L.) Skeels extracts: a systematized literature review focusing on dental applications

Medicinal plants are an important source of curative substances for the treatment of diseases. Investigations are focusing particularly on medicinal plants used to treat affections of the oral cavity. Among these species, there is evidence of potential applications of Syzygium cumini to Dentistry. The objective of this systematized literature review was to synthesize the evidence on the antimicrobial activity of this plant, as well cite some as the traditional uses of its extracts for dental purposes. The data indicate that the extracts prepared from different parts of the plant have antibacterial and antifungal effects on different pathogenic microorganisms of the oral microbiota and/or those that can potentially cause oral diseases, demonstrating a promising therapeutic potential for indication and use in Dentistry to prevent and/or treat oral affections. Descriptors: Plant Extracts; Medicine, Traditional; Anti-Bacterial Agents; Antifungal Agents; Dentistry.


INTRODUCTION
The use of medicinal plants for curative purposes is intrinsically related to the early days of medicine when they were used as a basis in the treatment of various diseases 1,2 . Medicinal plants have been for a long time the primary source of material for the production and development of drugs 3 . Although medicine is at an advanced technical and scientific stage in most parts of the world, 80% of the population of developing countries continues to primarily rely on traditional resources and practices for basic health care 4-6 .
In this scenario, considering the need for studies investigating medicinal plants with potential application to Dentistry 8,9 , the objective of this literature review was to synthesize the biological activities of potential interest for Dentistry of S. cumini, focusing on its antimicrobial and antifungal effects on microorganisms of the oral microbiota.

MATERIAL AND METHOD
This study consists of a literature review and bibliometric study of original articles evaluating the antibacterial and antifungal activities of S. cumini extracts on microorganisms of the oral microbiota and/or microorganisms that can potentially cause oral diseases, focusing on some uses and indications of these extracts with potential interest to Dentistry. o Search strategy For the literature review and bibliometric study, searches were performed in May 2018 using the National Library of Medicine National Institutes of Health (PubMed), Scientific Electronic Library Online (Scielo) and Google Scholar databases. Articles without publication date and language restrictions were selected. The following terms were used: "Syzygium cumini", "antifungal activity", "antimicrobial activity" through the search strategy using Boolean operators "AND" and "OR" as follows: "(Syzygium cumini) AND (antimicrobial activity OR antifungal activity)". o Inclusion and exclusion criteria Only complete literature reviews and experimental studies addressing the topic proposed and that had only used extracts from different parts of S. cumini were included for fulltext reading. Studies investigating compounds isolated from the plant or synthesized compounds were not considered. Incomplete articles, monographs, master's dissertations, doctoral theses and publications not consistent with the topic were excluded. Articles investigating S. cumini extracts combined with other substances were also eliminated. o Study selection Analysis and selection of the retrieved articles were performed in three steps. In the first step, the title of the articles was read and those whose title indicated studies related to the antimicrobial and antifungal potential of S. cumini extracts against oral microorganisms, as well as dental applications, were selected. The second step consisted of reading the abstracts of the selected articles. Finally, the third step consisted of full-text reading of the articles and qualitative analysis of the studies that addressed the topic proposed and met the eligibility criteria. Studies reporting some evidence on the subject of this investigation were selected.

RESULTS
The searches retrieved 5.337 articles, being 260 from PubMed, seven from Scielo and 5.110 from Google Scholar, respectively. After analysis of the title, 1.084 article were excluded and after this step, the abstracts of 174 articles were read and those that addressed the topic proposed and met the eligibility criteria were selected for full-text reading (61 articles). After exclusion of duplicated articles, evaluation and qualitative analysis of the articles retrieved a final sample of 42 articles, including studies related to the antibacterial and antifungal activities of S. cumini extracts against microorganisms of the oral microbiota and/or microorganisms that can potentially cause oral diseases ( Figure 1). Some findings about the popular use of S. cumini for therapeutic purposes and application of S. cumini extracts to Dentistry is described in Table 1. Evidence available in the literature on the antibacterial and antifungal effects attributed to the S. cumini extracts on microorganisms of the oral microbiota and/or microorganisms that can potentially cause diseases of the oral cavity is described in Tables 2 and 3, respectively.  Legend: *NS= not specified.   ;Saha et al. 25   Native to tropical regions, Syzygium cumini is found in several countries of the Asian, African and American continent 1,3,10,27 . The plant has recognized medicinal potential, including antidiabetic activity 10,11,18,27 and different other therapeutic purposes attributed to different pharmacological actions that can be obtained from parts of the plant such as seeds, leaves, stem and fruits 1,3,6,10-13,15-18, 27,31,35,50 . In addition, its medicinal applications also extend to the use of different parts for curative purposes of oral affections 1,10,14,[19][20][21][22]24 , with the demonstration of antibacterial and antifungal effects on oral microorganisms as corroborated by the literature findings mentioned earlier and showing the potencial applications of this plant to prevent and/or treat oral affections.
Thus, the antimicrobial effects on pathogenic microorganisms such as Streptococcus mutans 9,33 , other bacteria of the genus Streptococcus 47 , fungi of the genus Candida 2,9,47 and microorganisms associated with endodontic and periapical infections such as Enterococcus faecalis, Escherichia coli and Staphylococcus aureus 9 , as well as microorganisms associated with infections that can potentially affect the oral cavity, such as Neisseria gonorrhoeae 38 and Bacillus subtilis 9,43 , reinforce the promising medicinal effect of the S. cumini extract, indicating possible applications to the treatment of affections of the oral cavity like dental caries, periodontal disease, endodontic infections and oral candidiasis 9 . In addition, other biological activities such as antiinflammatory, antioxidant and anticarcinogenic effects 16 indicate a vast and promising therapeutic potential of the extracts of this plant that go beyond the antibacterial and antifungal effects highlighted here.

CONCLUSION
The present results permit us to state that, in addition to the popular use of different parts of S. cumini for therapies of interest and/or for application to Dentistry, the evidence of the antibacterial and antifungal effects of their extracts on different pathogenic oral microorganisms or those that can potentially affect this site, indicates that they present a potential therapeutic activity and may be used in Dentistry for the prevention and/or treatment of oral affections.