Mouthwashes: Alternatives and Future Directions.

This narrative review summarises "alternative" or "natural" over-the-counter (OTC) mouthwashes not covered elsewhere in this supplement and newly emerging products, as potential mouthwashes of the future. The "natural" mouthwashes reviewed include saltwater, baking soda, coconut oil, charcoal, propolis, seaweeds, and probiotics. Other than essential oils, it is apparent that their clinical effectiveness is still under debate, but there is some evidence to suggest that propolis reduces plaque and gingivitis. This review also covers the host immune response, via novel anti-inmmunomodulant mouthwashes, such as erythropoietin to reduce inflammation with oral mucositis (OM) after radiotherapy. The emerging concept of nanoparticle-containing mouthwashes, such as iron oxide, is further discussed for OM, this agent having the potential for more targeted delivery of chemical antimicrobials. Unfortunately, there are impacts on the environment of widening mouthwash use with more new products, including increased use of packaging, antimicrobial resistance, and possible detrimental effects on marine life. Further, there are roadblocks, relating to regularly approvals and side effects, that still need to be overcome for any OTC deivered immunomodulant or nanoformulation mouthwashes. Despite these caveats, there are many new mouthwashes under development, which could help manage major oral diseases such as caries, gingivitis, and periodontal disease.

The Role of Vitamins in Oral Potentially Malignant Disorders and Oral Cancer: A Systematic Review.

BACKGROUND: Micronutrients are vital for general and oral health, and their potential anti-cancer properties are documented. We explore beneficial vitamins for oral potentially malignant disorders (OPMDs) and oral cancer (OC), assessing the therapeutic impacts of essential vitamin supplementation. METHODS: We systematically review evidence on vitamin supplementation's therapeutic effects for OPMDs and OC. Relevant studies were identified through comprehensive searches of MEDLINE, Evidence-Based Medicine, and Web of Science until 16 May 2023. All studies underwent risk of bias using criteria modified from the Office of Health Assessment and Translation (OHAT) tool. RESULTS: We analysed 80 papers. Vitamin K, studied in vitro, shows promising therapeutic potential. Vitamin C, investigated in vivo (animals and humans), demonstrated mixed animal results and generally positive human trial effects. Vitamin A's efficacy varied, with positive monotherapy or adjunct effects. Vitamins B and D showed therapeutic benefits. Oral cancer research was extensive, with a focus on oral lichen planus and oral leukoplakia among the 11 OPMDs. All bias levels were reported in 'selective reporting' and 'performance', except for "definitely high" in the 'selection', 'detection', and 'attrition/exclusion' domains. CONCLUSIONS: Evidence of vitamin interventions for OPMDs and OC ranges from mixed to promising. Standardizing the study design and outcomes would enhance future research.

Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro.

Kava is a beverage made from the ground roots of the plant Piper Methysticum. Active compounds of Kava have previously been demonstrated to exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Our aim was to investigate the in vitro effects of the main constituents derived from Kava on oral squamous cell carcinoma (OSCC) activity. Gas chromatography mass spectrometry (GCMS) was used to characterise the main constituents of two Kava preparations. Cell proliferation was assessed in two human OSCC cell lines (H400 and BICR56) and in normal oral keratinocytes (OKF6) treated with the identified Kava constituents, namely Flavokawain A (FKA), Flavokawain B (FKB), yangonin, kavain and methysticin using an MTS in vitro assay. Cell migration at 16 h was assessed using a Transwell migration assay. Cell invasion was measured at 22 h using a Matrigel assay. Cell adhesion was assessed at 90 min with a Cytoselect Adhesion assay. The two Kava preparations contained substantially different concentrations of the main chemical constituents. Treatment of malignant and normal oral keratinocyte cell lines with three of the identified constituents, 10 µg/ml FKA, 2.5 µg/ml FKB and 10 µg/ml yangonin, showed a significant reduction in cell proliferation in both H400 and BICR56 cancer cell lines but not in normal OKF6 cells. Remarkably, the same Kava constituents induced a significant reduction of OSCC cell migration and invasion. We have demonstrated, for the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. This highlights an avenue for further research of Kava constituents in the development of future cancer therapies to prevent and treat OSCC.

Protective effect of kava constituents in an in vitro model of oral mucositis.

PURPOSE: Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model. METHODS: Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay. RESULTS: Pre-treatment of cells for 24 h with 2.5 µg/ml kavain and 5 µg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 µg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 µg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity. CONCLUSION: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.

The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review.

BACKGROUND: Kava is a beverage made from the ground roots of the plant Piper Methysticum and has long-held a significant place within Pacific island communities. Active compounds were extracted from kava, and secondary metabolites include kavalactones, chalcones, cinnamic acid derivatives and flavanones. It is thought that components of kava may exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. METHODS: We conducted a systematic review to summarize available evidence of the anticancer effects of kava components and investigate their potential use for oral squamous cell carcinoma (OSCC) treatment. Eligible studies were identified through a comprehensive search of OVID EMBASE, OVID MEDLINE and Web of Science, as at April 2018. RESULTS: Of 39 papers that met the inclusion criteria, 32 included in vitro models and 13 included animal studies. A total of 26 different cancers were assessed with 32 studies solely assessing epithelial cancers, 6 mesenchymal cancers and 1 study including both. There was only one report assessing an OSCC cell line. Antiproliferative properties were demonstrated in 32 out of 39 papers. The most researched constituent of kava was flavokavain B followed by flavokavain A. Both were associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins. Further, they were associated with a dose-dependent reduction of angiogenesis. CONCLUSION: There was heterogeneity of study models and methods of investigation across the studies identified. Components of kava appear to present an area of interest with chemotherapeutic potential in cancer prevention and treatment, particularly for epithelial neoplasms. To date, there is a paucity of literature of the utility of kava components in the prevention and treatment of oral squamous cell carcinoma.