Phytotherapy in the management of denture stomatitis: A systematic review and meta-analysis of randomized controlled trials.

Medicinal plant extracts are commonly applied for infectious diseases and are perceived as alternatives to conventional antimicrobial agents. We aimed to confirm the efficacy of phytotherapy for denture stomatitis compared with conventional therapies and placebo. A comprehensive literature search was conducted in Pubmed, Embase, Cochrane Library (CENTRAL), Scopus, and Web of Science, in addition to manual searching. Randomized controlled trials (RCTs) published in English, and studying the treatment of denture stomatitis with herbal medicines, were included. The outcome measures included the relief of clinical signs, reduced Candida colony counts, adverse effects, and patient satisfaction. Nineteen RCTs were included for a systematic review based on selection criteria. Two of them were analyzed using a random-effects model. There was no difference in the relief of clinical signs (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.43-2.15) and microbiological improvement (OR = 1.74; 95% CI: 0.55-5.45) between propolis and miconazole. Most of the included studies showed that phytomedicines had fewer side effects and more patient satisfaction than antifungals or disinfectants. However, further RCTs with more standardly prepared herbal formulations are required to verify the clinical efficacy of phytotherapy as an alternative or adjunctive therapy for denture stomatitis.

The Application of Small Molecules to the Control of Typical Species Associated With Oral Infectious Diseases.

Oral microbial dysbiosis is the major causative factor for common oral infectious diseases including dental caries and periodontal diseases. Interventions that can lessen the microbial virulence and reconstitute microbial ecology have drawn increasing attention in the development of novel therapeutics for oral diseases. Antimicrobial small molecules are a series of natural or synthetic bioactive compounds that have shown inhibitory effect on oral microbiota associated with oral infectious diseases. Novel small molecules, which can either selectively inhibit keystone microbes that drive dysbiosis of oral microbiota or inhibit the key virulence of the microbial community without necessarily killing the microbes, are promising for the ecological management of oral diseases. Here we discussed the research progress in the development of antimicrobial small molecules and delivery systems, with a particular focus on their antimicrobial activity against typical species associated with oral infectious diseases and the underlying mechanisms.

Ursolic acid inhibits multi-species biofilms developed by Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii.

OBJECTIVE: The current study aimed to assess the antimicrobial activity of ursolic acid (UA) against multi-species biofilms formed by Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii, as well as to measure its biocompatibility. METHODS: Crystal violet staining, CFU counting, CCK-8 assays and scanning electron microscopy (SEM) were applied to investigate the effect of UA on multi-species biofilms. UA's effect on exopolysaccharides (EPS) production was measured using confocal laser scanning microscopy (CLSM) and the anthrone-sulfuric acid method. Fluorescent in situ hybridization (FISH) was applied to visualize and quantify the microbial composition of multi-species biofilms. Quantitative real-time PCR (qRT-PCR) was used to measure the expression of virulence genes of S. mutans, S. sanguinis, and S. gordonii under UA treatment. Moreover, CCK-8 assays were performed to evaluate its cytotoxicity against human oral keratinocytes (HOKs) and human gingival epithelial cells (HGEs). RESULTS: The results showed that UA had significant antimicrobial activity against common oral streptococci. UA also reduced the EPS synthesis of oral streptococci and suppressed gtf genes' expression. In addition, UA reduced the proportion of S. mutans in multi-species biofilms. Besides, UA had low cytotoxicity against HOKs and HGEs. CONCLUSIONS: UA exhibited antibiofilm activity against oral pathogenic bacteria and had the potential to be used in dental caries treatment.

A Novel Small Molecule, LCG-N25, Inhibits Oral Streptococcal Biofilm.

Dental caries is a chronic oral infectious disease caused by cariogenic biofilm adhered on the tooth surface. Our previous study demonstrated that a repurposed natural compound napabucasin (NAP) showed good antimicrobial activity against oral streptococcal biofilms. The current study designed a novel small molecule, namely LCG-N25, using NAP as a lead compound, and aimed to investigate its potential as an antimicrobial agent in the control of dental caries. LCG-N25 was designed and synthesized with reference to the structure of NAP. The minimal inhibitory concentrations and the minimal bactericidal concentrations of LCG-N25 against Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii were evaluated by microdilution method. The antimicrobial activity of LCG-N25 was further evaluated by crystal violet staining, colony forming units counting, biofilm metabolism assay, dead/live fluorescent staining, and scanning electron microscopy. The effect of LCG-N25 on the extracellular polysaccharides of biofilms was determined by both anthrone-sulfuric acid method and fluorescent staining. The microbial composition of streptococcal biofilms after LCG-N25 treatment was further visualized and quantified by fluorescence in situ hybridization. Besides, the cytotoxicity of LCG-N25 was evaluated by Cell Counting Kit-8 assay, and repeated exposure of S. mutans to LCG-N25 treatment was performed to assess if this novel compound could induce drug resistance of this cariogenic bacterium. We found that LCG-N25 exhibited a good antibacterial activity, low-cytotoxicity, and did not induce drug resistance of cariogenic S. mutans. These findings suggest that LCG-N25 may represent a promising antimicrobial agent that can be used as an adjuvant to the management of dental caries.

Utilization of the extract of Cedrus deodara (Roxb. ex D.Don) G. Don against the biofilm formation and the expression of virulence genes of cariogenic bacterium Streptococcus mutans.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus deodara (Roxb. ex D.Don) G. Don is applied as anti-inflammatory and anti-infection agents in folklore medicine. AIM OF THE STUDY: The present study aimed to assess the antimicrobial activity of Cedrus deodara (Roxb. ex D.Don) G. Don extract (CDE) against Streptococcus mutans biofilm formation and its biocompatibility, as well as to identify its chemical components. MATERIALS AND METHODS: Confocal laser scanning microscopy (CLSM), crystal violet staining, and CFU counting assay were applied to investigate the effect of CDE on S. mutans biofilm formation and extracellular polysaccharides (EPS) synthesis. The microstructure of S. mutans biofilms formed on glass coverslips and bovine enamel treated with CDE was observed by scanning electron microscopy (SEM). qRT-PCR was used to measure the expression of virulence genes gtfB, gtfC, and gtfD, and zymogram assay was performed to investigate the enzymatic activity of Gtfs. Moreover, HPLC-MS and NMR were applied to identify its chemical components. CCK-8 assay was also performed on human oral cells to evaluate its biocompatibility. RESULTS: Under the treatment of CDE, S. mutans formed less biofilm on both coverslips and enamel surfaces and synthesized less EPS. Moreover, CDE downregulated the expression of gtf genes and inhibited the enzymatic activity of Gtfs. According to HPLC-MS and NMR results, molecular structures of six main compounds in CDE were identified. CDE also has a good biocompatibility. CONCLUSIONS: CDE exhibits inhibitory activity against S. mutans and a good biocompatibility. It has the potential to be developed as anti-caries agents for clinical use.

Rhodiola rosea extract inhibits the biofilm formation and the expression of virulence genes of cariogenic oral pathogen Streptococcus mutans.

OBJECTIVE: The present study aimed to evaluate the effect of Rhodiola rosea extract (RE) on Streptococcus mutans biofilm formation and the relevant mechanism of its action. METHODS: The effect of RE on the biofilm formation and extracellular polysaccharides (EPS) synthesis of S. mutans was assessed by confocal laser scanning microscopy (CLSM), crystal violet staining and CFU counting method. Scanning electron microscopy (SEM) was applied to observe the surface morphology of S. mutans biofilms formed on glass coverslips and dental enamel. To study the relevant mechanism, quantitative real time PCR (qRT-PCR) and zymogram assay were applied to measure the expression of virulence genes and the enzymatic activity of glucosyltransferases (Gtfs) under the treatment of RE. The CCK-8 assay was also performed on macrophages (RAWs) and human oral keratinocytes (HOKs) in order to evaluate its biocompatibility. RESULTS: As a result, RE inhibited the biofilm formation and EPS synthesis of S. mutans. RE also suppressed the expression of gtf genes and quorum sensing (QS) system as well as the enzymatic activity of Gtf proteins. Moreover, RE exhibited a good biocompatibility to human cells. CONCLUSIONS: This study provides the evidence for RE as a novel anti-biofilm agent for clinical use.