Periodontitis is one of the most extensive oral problems that affect human population, resulting from an inflammatory response against microorganisms involved with plaque accumulation on the subgingival dental surface. The development of the process depends on the interaction between the bacteria in the site of infection. The presence of an oral biofilm composed by bacteria and their products includes also lipopolysaccharides and proteinases that are responsible for the progression of periodontitis. Bacteria stimulate host immunopathological and inflammatory mechanisms that result in the destruction of the periodontal tissue [
Different strategies have been used to treat periodontal diseases. Mechanical therapy and surgical procedures reduce microbial burden, being effective in the control of the periodontitis progression. Nevertheless, this regulation is not always satisfactory, possibly due to the prominent role of immunogenetic response on periodontal destruction. In some cases, adjunctive therapies may be required [
Medicinal plants have been fundamental for thousands of years to provide bioactive molecules used to treat different types of human infirmities, such as inflammation, pain, and tumors. Also, they can be a source of compounds to be tested in the treatment of periodontal diseases. Nowadays, there is an increasing number of scientific investigation exploring plant extracts or purified molecules in periodontal diseases [
The aim of this systematic review was to investigate the advances in the study of medicinal plants and the development of induced periodontitis in animal models. Data were described and discussed in order to evaluate the limitation and also the perspectives of the application of these agents in the treatment of the periodontal disease.
A systematic search was conducted by three independent researchers who screened articles published up to March/2016 in order to identify the studies that contained sufficient and clear information on the association of the medicinal plants and periodontitis in murine models. The searches were performed using PubMed (
Search flowchart and selection of articles for the review of the literature.
Table
List of medicinal plants, experimental methods, and their biological effects on induced periodontitis.
Plant species | Plant material | Route of administration | Animal used |
Type of induction/time of analysis | Antibacterial effect1 | Bone loss/method2 | Anti-inflammatory activity3 | Reference |
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Mixture of extracts (9 : 1 weight) | Oral |
|
Injecting |
Not evaluated | Reduced ABC/ |
Reduced the |
Almeida et al. [ |
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Tulsi extract | Topical |
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Silk ligature/9 days | Not evaluated | Not reduced ABC/Stereo | Presented anti-inflammatory activity in another experimental model | Hosadurga et al. [ |
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Baicalin | Oral |
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Nylon ligature/7 days | Not evaluated | Reduced ABC/histology | Not evaluated | Cai et al. [ |
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Berberine | Oral |
|
Silk ligature/8 days | Not evaluated | Reduced ABC/ |
Not evaluated | Tu et al. [ |
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LongoVital® | Oral |
|
Injecting |
Not evaluated | Reduced ABC/Radio | Not evaluated | Klausen et al. [ |
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Mangiferin |
Oral |
|
Cotton ligature/1, 4, and 7 days | Not evaluated | Reduced ABC/histology | Inhibited COX-2 expression, the rolling, and adhesion of leukocytes in the periodontal tissue | Carvalho et al. [ |
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Curcumin |
Gavage |
|
Nylon ligature/30 days | Not evaluated | Reduced ABC/histology | Reduced the expression of TNF- |
Zhou et al. [ |
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Magnolol |
Oral |
|
Silk ligature/9 days |
|
Reduced ABC/ |
Inhibited neutrophil migration, MPO activity, and COX-2 and iNOS expression in gingival tissues | Lu et al. [ |
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Bu-Shen-Gu-Chi-Wan |
Oral |
|
Injecting |
Not evaluated | Improved the mineral density of the bone/ |
Reduced levels of IL-1 |
Yang et al. [ |
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Pycnogenol® |
Oral | Balb/c (male) | Injecting |
Antibacterial activity against |
Reduced ABC/Stereo | Not evaluated | Sugimoto et al. [ |
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Aqueous extract containing tannin and phenolic compounds | Oral |
|
Injecting |
Anti-adhesive properties against |
Not evaluated | Reduced |
Polak et al. [ |
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Curcumin | Topical |
|
Silk ligature/28 days | Not evaluated | Did not reduce ABC/Stereo | Exhibited anti-inflammatory activity in another experimental model | Hosadurga et al. [ |
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Extract containing Catechin | Topical |
|
Injecting |
Not evaluated | Did not reduce ABC/histology | Reduced inflammatory cell infiltration and levels of TNF- |
Maruyama et al. [ |
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Aqueous extract | Oral |
|
Injecting |
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Reduced ABC/Stereo | Not evaluated | Toyama et al. [ |
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Andiroba oil | Oral |
|
Cotton ligature/50 days | Not evaluated | Did not reduce ABC/histology | Reduced the quantity of inflammatory cells in histology | Carmona et al. [ |
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Oral |
|
Nylon ligature/1 day | Not evaluated | Not evaluated | Reduced gingival TNF- |
Holanda Pinto et al. [ |
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Extract containing Catechin | Oral |
|
Nylon ligature/7, 14, and 28 days | Not evaluated | Reduced ABC/histology | Reduced |
Cho et al. [ |
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Mixture of dichloromethane and methanol extract | Topical |
|
Cotton ligature/11 days |
|
Did not reduce ABC/Stereo | Not evaluated | Barrella et al. [ |
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Mixture of leaf essential oil and hydroalcoholic solution from bark | Topical |
|
Nylon ligature/11 days | Prevented the growth of oral microorganisms from gingival tissue | Reduced ABC/histology | Reduced MPO activity and inhibited TNF- |
Botelho et al. [ |
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Carvacrol | Topical |
|
Nylon ligature/11 days | Prevented the growth of oral microorganisms from gingival tissue | Reduced ABC/AFM | Reduced MPO activity in gingival tissue | Botelho et al. [ |
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Methanolic extract | Oral |
|
Silk ligature /8 days | Not evaluated | Reduced ABC/Stereo | Reduced inflammatory cell infiltration, vascular permeability, expression of NF- |
Paterniti et al. [ |
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Essential oil | Topical |
|
Cotton ligature/11 days | Reduced |
Reduced ABC/histology | Increment in the |
Pimentel et al. [ |
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Extract containing Catechin | Topical |
|
Injecting |
Not evaluated | Reduced ABC/histology | Reduced inflammatory cell infiltration | Yoshinaga et al. [ |
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Cocoa extract containing flavonoids | Oral |
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Cotton ligature/28 days | Not evaluated | Reduced ABC/histology | Reduced/oxidized glutathione ratio and neutrophil infiltration | Tomofuji et al. [ |
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Ethanol extract | Subcutaneous |
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Nylon ligature/30 days | Not evaluated | Reduced the furcation region/histology | Reduced neutrophil accumulation in the gingival tissue | Benatti et al. [ |
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Anethole | Intraperitoneal |
|
Injecting |
Not evaluated | Not evaluated | Reduced serum levels of IL-1 |
Moradi et al. [ |
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Modified curcumin | Gavage |
|
Injecting |
Not evaluated | Reduced ABC/Stereo, and |
Reduced serum level of IL-1 |
Elburki et al. [ |
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|
Product of |
Oral |
|
Silk ligature/8 days | Not evaluated | Reduced ABC/Stereo | Reduced NF- |
Paola et al. [ |
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|
Oral |
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Silk ligature/11 days | Not evaluated | Reduced ABC/histology | Not evaluated | Sezer et al. [ |
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Curcumin | Gavage |
|
Cotton ligature/15 days | Not evaluated | Did not reduce ABC/ |
Reduced the inflammatory cell infiltrate to gingival tissue | Guimarães et al. [ |
The majority of articles (43.3%) described studies conducted with plant extracts, 40% with purified compounds and 16.6% with a mixture of two or more plant extracts. Among them, six articles described experiments developed using a commercial product [
In general, studies were preferentially conducted using
Taking into consideration the sex of the animal, most authors chose to use males (86.6%). Two articles described the use of females [
Regarding the common type of periodontitis-induction, in 66.6% of the articles, the process was caused by ligature (silk: 23.3%, nylon: 23.3%, and cotton: 20%). This method is widely used because it facilitates the accumulation of biofilm. This procedure increases the infiltration of inflammatory cells and the production of chemical mediators that lead to the degradation of the tissues around the teeth contributing to the destruction of the periodontal tissues [
Some of the studies analyzed described that long periods of experimental design were utilized to properly investigate the severity of tissue destruction during periodontal disease treatment: 63 days [
More than 66% of studies chose the oral administration to evaluate the efficacy of the plant material. The topical administration was described by 26.6% of the studies and 6.9% treated animals through subcutaneous or intraperitoneal cavity injections. The route of administration is an important parameter to influence the efficacy of the material since it can interfere with the sufficient amount of substance available to promote the biological effects. As observed, different results were seen for alveolar bone loss of animals submitted to the treatment with an extract containing Catechin obtained from
Periodontal disease initiation and progression occur as a consequence of the host response to microorganisms of the dental biofilm [
The alveolar bone loss is one of the most important parameters evaluated in the induced periodontal disease. From 30 selected articles, 27 evaluated the ability of the plant material to promote a significant reduction of the bone loss. Carvacrol purified from
It is noteworthy that the reduction of the inflammatory process may be associated with a reduced bone loss [
Although there is a close relation between the bone reabsorption and the inflammatory response, we suggest that the negative results of some of substances analyzed should be attributed to the fact that they do not act in the osteoclastogenesis process. This information is supported by the personal observation conducted using sulphated polysaccharides recovered from red marine algae
It is important to mention that, although many plant substances may have deleterious effects to different animal organs [
Finally, 8 of the 30 selected articles conducted their experiments with a gel-based formulation containing the plant material investigated. In these experiments, the authors administered the gel topically, generally three times a day. The main idea behind these investigations is to reveal the further potential of the combined gel preparation to combat periodontal disease in closer than clinical situations. This was the outlook investigated in the studies published by [
In conclusion, the selected studies presented a large diversity of experimental designs, concerning the type of induction, time of analysis, and methods used for the evaluation of alveolar bone loss, anti-inflammatory, and antibacterial activities. None of the studies evaluated the possible toxic effects associated with the administration of the material analyzed or their ability to prevent damages to organs caused by systemic effects of induced periodontitis. Gel-based formulations present an interesting strategy to treat periodontitis; however, further studies are necessary to clarify its usefulness in the clinical situation.
The authors declare that they have no conflict of interests.
This research is supported by the Federal University of Piauí (UFPI-Edital PIBIC 2014/2015 and BIAMA 03/2014), CNPq (455104/2014-0). The authors thank teacher Abilio Borghi for the grammar review of the paper.