[Anti-Candida activity of aroma candy and its protective activity against murine oral candidiasis].

A daily eatable candy that has possible protective activity against oral candidiasis was experimentally produced. The candy was made from reduced-maltose as main constituent and from several natural products, such as oligonol (depolymerized polyphenols derived from lychee), cinnamon (cassia), citral, and capric acid, which are known to have anti-Candida activity in vitro and in vivo. The candy effectively inhibited the mycelial growth of C. albicans, even when it was diluted 1,000 times with culture media. We assessed the protective activity of the candy against murine candidiasis. When 50µl of candy dissolved and diluted 4 times with water was administered 3 times into the oral cavity of Candida infected mice, the score of lesions on the Candida-infected tongues improved on day 2. These findings suggest that this candy has potential as food that provides protective activity against oral candidiasis.

Suppression of inflammatory reactions by terpinen-4-ol, a main constituent of tea tree oil, in a murine model of oral candidiasis and its suppressive activity to cytokine production of macrophages in vitro.

The onset of oral candidiasis is accompanied by inflammatory symptoms such as pain in the tongue, edema or tissue damage and lowers the quality of life (QOL) of the patient. In a murine oral candidiasis model, the effects were studied of terpinen-4-ol (T-4-ol), one of the main constituents of tea tree oil, Melaleuca alternifolia, on inflammatory reactions. When immunosuppressed mice were orally infected with Candida albicans, their tongues showed inflammatory symptoms within 24 h after the infection, which was monitored by an increase of myeloperoxidase activity and macrophage inflammatory protein-2 in their tongue homogenates. Oral treatment with 50 µL of 40 mg/mL terpinen-4-ol 3h after the Candida infection clearly suppressed the increase of these inflammatory parameters. In vitro analysis of the effects of terpinen-4-ol on cytokine secretion of macrophages indicated that 800 µg/mL of this substance significantly inhibited the cytokine production of the macrophages cultured in the presence of heat-killed C. albicans cells. Based on these findings, the role of the anti-inflammatory action of T-4-ol in its therapeutic activity against oral candidiasis was discussed.

[Effects of inhibitory activity on mycelial growth of Candida albicans and therapy for murine oral candidiasis by the combined use of terpinen-4-ol and a middle-chain fatty acid, capric acid].

The combined effect of terpinen-4-ol, the main component of tea tree oil, and capric acid against mycelial growth of Candida albicans and murine oral candidiasis was evaluated in vitro and in vivo. Mycelial growth of C. albicans was estimated by the Cristal violet method. Combination of these compounds revealed a potent synergistic inhibition of growth. Therapeutic efficacy of the combination was evaluated microbiologically in murine oral candidiasis, and its application of the compounds clearly demonstrated therapeutic activity. Based on these results, the combined agent of terpinen-4-ol and capric acid was discussed as a possible candidate for oral candidiasis therapy.

[Inhibition of Candida mycelia growth by a medium chain fatty acids, capric acid in vitro and its therapeutic efficacy in murine oral candidiasis].

We assessed anti-C. albicans activities of the 4 fatty acids : caproic acid, caprylic acid, capric acid and lauric acid in vitro. All four inhibited not only the mycelial but also the yeast-form growth of Candida albicans. In particular, capric acid and caprylic acid inhibited Candida mycelia growth at very low concentrations. The effects of treatment of these two fatty acids on oral candidiasis were examined using a murine model. When 50 µl of capric acid (more than 48.8 µM) was administered three times into the oral cavity of Candida-infected mice, symptom scores of tongues of the mice were significantly improved. Histological studies of the capric acid-treated animals indicated that the fatty acid suppressed mycelial growth of the fungus on the tongue surface. These results suggest that all four fatty acids, and especially capric acid, have potential as substances supporting anti-Candida treatment.

Effect of Streptococcus salivarius K12 on the in vitro growth of Candida albicans and its protective effect in an oral candidiasis model.

Oral candidiasis is often accompanied by severe inflammation, resulting in a decline in the quality of life of immunosuppressed individuals and elderly people. To develop a new oral therapeutic option for candidiasis, a nonpathogenic commensal oral probiotic microorganism, Streptococcus salivarius K12, was evaluated for its ability to modulate Candida albicans growth in vitro, and its therapeutic activity in an experimental oral candidiasis model was tested. In vitro inhibition of mycelial growth of C. albicans was determined by plate assay and fluorescence microscopy. Addition of S. salivarius K12 to modified RPMI 1640 culture medium inhibited the adherence of C. albicans to the plastic petri dish in a dose-dependent manner. Preculture of S. salivarius K12 potentiated its inhibitory activity for adherence of C. albicans. Interestingly, S. salivarius K12 was not directly fungicidal but appeared to inhibit Candida adhesion to the substratum by preferentially binding to hyphae rather than yeast. To determine the potentially anti-infective attributes of S. salivarius K12 in oral candidiasis, the probiotic was administered to mice with orally induced candidiasis. Oral treatment with S. salivarius K12 significantly protected the mice from severe candidiasis. These findings suggest that S. salivarius K12 may inhibit the process of invasion of C. albicans into mucous surfaces or its adhesion to denture acrylic resins by mechanisms not associated with the antimicrobial activity of the bacteriocin. S. salivarius K12 may be useful as a probiotic as a protective tool for oral care, especially with regard to candidiasis.

Therapeutic effects of cinnamaldehyde and potentiation of its efficacy in combination with methylcellulose on murine oral candidiasis.

We examined the therapeutic effects of cinnamaldehyde and the potentiation of those effects with cassia and cinnamaldehyde when combined with the food additive methylcellulose against murine oral candidiasis. When 19.5mg/ml of cinnamaldehyde was administered in the oral cavity of Candida infected mice, the oral symptoms were improved. Furthermore, when either a cassia or a cinnamaldehyde preparation in combination with methylcellulose was administered to oral candidiasis-inflicted mice, the therapeutic effects of cassia or cinnamaldehyde potentiated. Methylcellulose itself did not affect the oral symptoms or the viable number of C. albicans cells. GC/MS analysis showed that the dose of cinnamaldehyde remaining in the tongue tissue of mice treated with the cinnamaldehyde-methylcellulose mixture was higher than that in mice administered cinnamaldehyde alone, and also showed that cinnamaldehyde was not detected in the blood of any of the tested mice. These findings suggested that the combination of cassia or cinnamaldehyde and methylcellulose may be a useful prophylactic or therapeutic tool against oral candidiasis.

Enhanced immobilization of acidic proteins in the apatite layer via electrostatic interactions in a supersaturated calcium phosphate solution.

Artificial materials coated with a protein-apatite composite layer have great potential in clinical applications as a third generation biomaterial. Such composite materials can be prepared by immersing a surface modified substrate into a supersaturated calcium phosphate solution (CP solution: 142 mM NaCl, 3.75 mM CaCl(2), 1.5mM K(2)HPO(4)·3H(2)O, buffered at pH 7.4 at 25 °C with tris(hydroxymethyl)aminomethane and HCl) supplemented with a protein. In the present study proteins of various molecular weights (MW) and isoelectric points (pI) were used to form a protein-apatite composite layer on a polymeric material to determine how the molecular properties of the protein affect the efficiency of protein immobilization (i.e. the amount of immobilized protein in the apatite layer as a percentage of the total amount of protein in solution). The results indicated that the efficiency of protein immobilization did not correlate with the MW of the protein. In contrast, the efficiency of protein immobilization was strongly related to the pI of the protein. As the pI decreased the efficiency of protein immobilization increased due to the high adsorption affinity of negatively charged acidic proteins for positively charged apatite crystals and/or apatite precursors in the CP solution. Thus, the use of acidic rather than basic proteins improves the immobilization efficiency in the present coating process.

Suppression of neutrophil recruitment in mice by geranium essential oil.

BACKGROUND: In aromatherapy, essential oils are used as anti-inflammatory remedies, but experimental studies on their action mechanisms are very limited. AIMS OF THE STUDY: To assess their anti-inflammatory activities, the effects of essential oils on neutrophil recruitment in mice were examined in vivo. METHOD: The effect of essential oils on leukocyte and neutrophil recruitment induced 6 h after intraperitoneal injection of casein in mice was examined. RESULTS: Leukocyte recruitment into the peritoneal cavity in mice was suppressed by intraperitoneal injections of geranium, lemongrass and spearmint oils at the dose of 5 microl/mouse, but was not by tea tree oil. This recruitment was inhibited dose-dependently by geranium oil. The suppression of leukocyte recruitment resulted from inhibition of neutrophil accumulation. CONCLUSION: Some essential oils used as anti-inflammatory remedies suppress neutrophil recruitment into the peritoneal cavity in mice.