The relationship between subjective oral frailty and adverse health outcomes or medical and dental expenditures in the latter-stage older adult: A 6-year longitudinal study.

OBJECTIVES: The study aimed to investigate the relationship between subjective oral frailty and adverse health outcomes or medical and dental expenditures in the latter-stage older adult through a 6-year longitudinal study. METHODS: The participants enrolled in the cross-sectional study were 3564 Tokushima City residents aged 75, 80, 85, and 90 years old who received oral health examinations and who responded to a questionnaire on oral conditions and health behavior at baseline. The data for the occurrence of disability or mortality, and the monthly medical expenditures, dental expenditures, and total medical expenditure of each participant were obtained from the National Health Insurance Database. RESULTS: The total medical expenditure showed significant differences in participants who had difficulties in eating tough foods, difficulties in swallowing tea or soup, and dry mouth when compared to that of healthy participants, in addition to the current medical treatment against the general disease. The 6-year longitudinal study revealed that participants with subjective oral frailty symptoms, including difficulties in eating tough foods and difficulties in swallowing tea or soup at baseline, had significantly higher medical, dental, and total expenditures among 538 participants without certified nursing care. In addition, those with subjective oral frailty or with less than 19 teeth present were shown to have a higher possibility for the occurrence of disability or mortality by the cox proportional hazard analysis. Furthermore, it was found that medical and total expenditures in older adults with adverse health outcomes were higher than that of healthy participants. CONCLUSION: These results suggest that subjective oral frailty in the latter-stage older adult is related to subsequent adverse health outcomes and an increase in medical and dental expenditures.

Oral care tablet containing kiwifruit powder affects tongue coating microbiome.

OBJECTIVES: Tongue coating, a kind of biofilm formed on the tongue dorsum, is the cause of various clinical conditions, such as oral halitosis and periodontal diseases, because Fusobacterium nucleatum acts as a bridge between other oral bacteria and periodontopathogenic bacteria in biofilm formation. Our previous clinical study revealed that taking oral care tablets containing kiwifruit powder significantly reduced not only tongue-coating index and volatile sulfur compounds but also total bacteria and F. nucleatum in tongue coating. In this study, we analyzed the microbiome of tongue coating samples obtained before and after oral care tablets intake to clarify whether this tablet is a useful tool for daily tongue care. METHODS: Thirty-two healthy young adults were enrolled, and a crossover clinical trial was conducted. We instructed subjects to remove tongue coating by tongue brush for intervention I, to keep the oral care tablet containing kiwifruit powder on the tongue dorsum and to let it dissolve naturally for intervention II. Microbial DNA was isolated from the collected tongue coating samples in each subject, then 16S rRNA next-generation sequencing, operational taxonomic unit clustering, and statistical analysis were performed. RESULTS: The microbiome analysis revealed that the oral care tablet in intervention II prompted a significant change in the tongue microbiota composition, a significant reduction in the relative abundance of Prevotella and Porphyromonas, and an increase in Firmicutes/Bacteroidetes ratio when compared to that in intervention I. CONCLUSION: These results suggested that the oral care tablet might contribute to the improvement of the oral condition due to its good influence on the tongue coating microbiome.

Effectiveness of an oral care tablet containing kiwifruit powder in reducing oral bacteria in tongue coating: A crossover trial.

OBJECTIVES: The aim of this study was to investigate the effect of an oral care tablet containing kiwifruit powder on oral bacteria in tongue coating compared with tongue brushing. MATERIAL AND METHODS: Thirty-two healthy, young adults were enrolled, and a crossover clinical trial was conducted. The volatile sulfur compound (VSC) concentration, Winkel tongue-coating index (WTCI), and the number of total bacteria in addition to Fusobacterium nucleatum in tongue coating were measured. We instructed subjects to remove tongue coating by tongue brush for Intervention I, to keep the oral care tablet containing kiwifruit powder on the tongue dorsum and to let it dissolve naturally for Intervention II, and three oral care tablets 1 day before the measurement for Intervention III. RESULTS: There were significant differences in terms of the level of H2 S, VSC, and WTCI at Intervention I and all evaluation values at Intervention II. There were significant differences in terms of the level of H2 S, VSC, WTCI, the number of total bacteria, and F. nucleatum at Intervention III. The value of WTCI, the number of bacteria, and F. nucleatum decreased significantly after taking the oral care tablets than after tongue brushing. When compared with Interventions I and III, Intervention III showed the effective results; there were significant differences in the number of total bacteria and F. nucleatum between tongue brushing and taking tablets. CONCLUSIONS: These results suggested that the oral care tablet containing kiwifruit powder could be effective in reducing total bacteria and F. nucleatum in tongue coating when compared with tongue brushing.

Impact of the use of Kampo medicine in patients with esophageal cancer during chemotherapy:a clinical trial for oral hygiene and oral condition.

OBJECTIVE: The aim of this study was to investigate the impact of the use of two Kampo medicines on oral mucositis, tongue coating bacteria, and gingiva condition in patients with esophageal cancer undergoing chemotherapy. METHODS: Twenty-three esophageal cancer patients who receive chemotherapy at Tokushima University Hospital, were included. The participants, who received professional oral healthcare, were randomly divided into three groups:7 subjects received Daiokanzoto sherbets, 7 subjects received Hangeshashinto sherbets, and 9 subjects received nothing (control). The numbers of total bacteria and specific periodontopathogenic bacteria in tongue coating were determined in addition to clinical parameters. RESULTS: No difference on the onset of oral mucositis was found among the three groups. However, tongue coating index, gingival index (GI), plaque index, the number of total bacteria, Fusobacterium nucleatum and Campylobacter rectus were decreased during chemotherapy. More specifically, GI as well as the number of F. nucleatum and C. rectus were decreased significantly in the Daiokanzoto group when compared to the control group (psize 8 < 0.05). No such differences were observed for the group receiving Hangeshashinto. CONCLUSION: This clinical trial showed that Daiokanzoto might be effective in attenuating gingival inflammation and reducing the levels of periodontopathogenic bacteria in patients with esophageal cancer. J. Med. Invest. 65:184-190, August, 2018.

A Review of Evidence for a Therapeutic Application of Traditional Japanese Kampo Medicine for Oral Diseases/Disorders.

Kampo medicines prescribed by specialized medical practitioners and Japanese physicians have gradually reemerged in Japan as alternatives to Western medications. Kampo formulations are composed of several plant extracts and, as such, the broad variety of phytochemicals they contain likely act synergistically to provide their beneficial effects. Kampo medicines have traditionally been prescribed for a number of health conditions, including chronic hepatitis, bronchial asthma, anemia, etc. The aim of this article is to review the beneficial effects of Kampos with respect to oral health. Pertinent papers published between 1970 and 2017 were retrieved by searching in PubMed, ScienceDirect, Web of Science, and Scopus using key words followed by evaluation of the relevant articles. In vitro studies have identified a number of properties that give credence to the potential of Kampos for treating or preventing oral diseases/disorders. Given their anti-microbial and anti-inflammatory properties, they may be promising agents for controlling periodontal diseases, oral mucositis, xerostomia, and drug-induced gingival overgrowth. Since some oral diseases have a complex etiology that involves microbial pathogens and the host immune response, agents with dual functionality such as Kampo phytochemicals may offer a therapeutic advantage.

The Daiokanzoto (TJ-84) Kampo Formulation Reduces Virulence Factor Gene Expression in Porphyromonas gingivalis and Possesses Anti-Inflammatory and Anti-Protease Activities.

Kampo formulations used in Japan to treat a wide variety of diseases and to promote health are composed of mixtures of crude extracts from the roots, bark, leaves, and rhizomes of a number of herbs. The present study was aimed at identifying the beneficial biological properties of Daiokanzoto (TJ-84), a Kampo formulation composed of crude extracts of Rhubarb rhizomes and Glycyrrhiza roots, with a view to using it as a potential treatment for periodontal disease. Daiokanzoto dose-dependently inhibited the expression of major Porphyromonas gingivalis virulence factors involved in host colonization and tissue destruction. More specifically, Daiokanzoto reduced the expression of the fimA, hagA, rgpA, and rgpB genes, as determined by quantitative real-time PCR. The U937-3xκB-LUC monocyte cell line transfected with a luciferase reporter gene was used to evaluate the anti-inflammatory properties of Daiokanzoto. Daiokanzoto attenuated the P. gingivalis-mediated activation of the NF-κB signaling pathway. It also reduced the secretion of pro-inflammatory cytokines (IL-6 and CXCL8) by lipopolysaccharide-stimulated oral epithelial cells and gingival fibroblasts. Lastly, Daiokanzoto, dose-dependently inhibited the catalytic activity of matrix metalloproteinases (-1 and -9). In conclusion, the present study provided evidence that Daiokanzoto shows potential for treating and/or preventing periodontal disease. The ability of this Kampo formulation to act on both bacterial pathogens and the host inflammatory response, the two etiological components of periodontal disease, is of high therapeutic interest.

Preventive effect of Daiokanzoto (TJ-84) on 5-fluorouracil-induced human gingival cell death through the inhibition of reactive oxygen species production.

Daiokanzoto (TJ-84) is a traditional Japanese herbal medicine (Kampo formulation). While many Kampo formulations have been reported to regulate inflammation and immune responses in oral mucosa, there is no evidence to show that TJ-84 has beneficial effects on oral mucositis, a disease resulting from increased cell death induced by chemotherapeutic agents such as 5-fluorouracil (5-FU). In order to develop effective new therapeutic strategies for treating oral mucositis, we investigated (i) the mechanisms by which 5-FU induces the death of human gingival cells and (ii) the effects of TJ-84 on biological events induced by 5-FU. 5-FU-induced lactate dehydrogenase (LDH) release and pore formation in gingival cells (Sa3 cell line) resulted in cell death. Incubating the cells with 5-FU increased the expression of nucleotide-binding domain and leucine-rich repeat containing PYD-3 (NLRP3) and caspase-1. The cleavage of caspase-1 was observed in 5-FU-treated cells, which was followed by an increased secretion of interleukin (IL)-1ß. The inhibition of the NLRP3 pathway slightly decreased the effects of 5-FU on cell viability and LDH release, suggesting that NLRP3 may be in part involved in 5-FU-induced cell death. TJ-84 decreased 5-FU-induced LDH release and cell death and also significantly inhibited the depolarization of mitochondria and the up-regulation of 5-FU-induced reactive oxygen species (ROS) and nitric oxide (NO) production. The transcriptional factor, nuclear factor-κB (NF-κB) was not involved in the 5-FU-induced cell death in Sa3 cells. In conclusion, we provide evidence suggesting that the increase of ROS production in mitochondria, rather than NLRP3 activation, was considered to be associated with the cell death induced by 5-FU. The results also suggested that TJ-84 may attenuate 5-FU-induced cell death through the inhibition of mitochondrial ROS production.

The Kampo medicine Rokumigan possesses antibiofilm, anti-inflammatory, and wound healing properties.

Periodontal diseases, which are inflammatory diseases of bacterial origin affecting the tooth-supporting tissues, are characterized by inflammation and destruction of gingival connective tissue and alveolar bone, and may lead to tooth loss. The aim of the study was to investigate Rokumigan, a Kampo Japanese traditional medicine made of six different plants, for its capacity to prevent biofilm formation by Fusobacterium nucleatum, to inhibit interleukin-6 (IL-6) and interleukin-8 (IL-8) secretion by mucosal cells, and to promote wound healing in a fibroblast model. Using a microplate colorimetric assay, Rokumigan prevented biofilm formation by F. nucleatum, while it had no effect on bacterial growth. Rokumigan inhibited IL-6 secretion in both epithelial cells and fibroblasts stimulated with lipopolysaccharide. However, it caused no significant inhibition of IL-8 secretion by both cell types. Rokumigan significantly increased proliferation and migration of gingival fibroblasts in a wound healing assay. In conclusion, the Kampo formulation Rokumigan, through suppression of biofilm formation by F. nucleatum, inhibition of IL-6 secretion by gingival epithelial cells and fibroblasts, and promotion of wound healing in a fibroblast model, may have potential application for periodontal diseases.

Effects of Japanese traditional herbal medicines (Kampo) on growth and virulence properties of Porphyromonas gingivalis and viability of oral epithelial cells.

CONTEXT: Kampos, commonly used in Japanese traditional medicine, are standardized herbal mixtures that have been used for centuries to treat a variety of ailments. We hypothesized that Kampos may have unidentified properties that may be beneficial in periodontitis, an inflammatory disease affecting the tooth-supporting tissues. OBJECTIVE: The aim of our study was to investigate various Kampos and their natural ingredients for their effects on Porphyromonas gingivalis growth, adherence to epithelial cells and proteinase activity. In addition, their effects on oral epithelial cell viability were evaluated. MATERIALS AND METHODS: Growth inhibition of P. gingivalis by various Kampos and their natural ingredients was evaluated by a microdilution broth assay method. Their effects on P. gingivalis proteinase activity and adherence to oral epithelial cells were determined by fluorometric assays. The cytotoxicity of test compounds towards oral epithelial cells was evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. RESULTS: Of the 27 Kampos tested, 7 were found to inhibit the growth of P. gingivalis. The lowest minimal inhibitory concentration (MIC) (250 µg/ml) was obtained with TJ-113. Analysis of the composition of the seven active Kampos showed that they contain Chinese rhubarb as a common ingredient. Therefore, additional growth inhibitory assays on P. gingivalis were carried out with purified anthraquinones known to be present in rhubarb. Aloe-emodin and rhein possessed the strongest antibacterial effects towards P. gingivalis with an MIC of 0.78 µg/ml. The seven Kampos containing rhubarb and purified anthraquinones also exhibited the capacity to decrease the adherence of P. gingivalis to oral epithelial cells and to reduce its proteinase activity. The most important anti-adherence effect of Kampo was obtained with TJ-126; at 250 µg/ml it reduced adherence of P. gingivalis to epithelial cells by 83%. Purified anthraquinones were found to be less active than Kampos. Kampo TJ-113 was found to be the most effective for inhibition of gelatin degradation (49% inhibition at 62.5 µg/ml). Again, purified anthraquinones inhibited gelatin degradation to a lesser extent. Lastly, none of the tested compounds showed cytotoxicity towards oral epithelial cells at the effective concentrations. CONCLUSION: Kampos containing rhubarb and its anthraquinone derivatives may represent promising molecules for controlling periodontal diseases through their capacity to inhibit P. gingivalis growth and virulence properties.