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Antifungal, cytotoxic, and immunomodulatory properties of tea tree oil and its derivative components: potential role in management of oral candidosis in cancer patients.

Ramage G, Milligan S, Lappin DF, Sherry L, Sweeney P, Williams C, Bagg J, Culshaw S - Front Microbiol (2012)

Bottom Line: The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation.Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol.These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms.

View Article: PubMed Central - PubMed

Affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, UK.

ABSTRACT
Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation. TTO and its derivatives were examined against 100 clinical strains of C. albicans. Planktonic minimum inhibitory concentrations (MICs) were determined using the CLSI M-27A broth microdilution method. Sessile MICs were determined using an XTT reduction assay. Inhibition, time-kill, and mode of action studies were performed. OKF6-TERT2 epithelial cells were used for cytotoxicity and cytokine expression assays. Planktonic C. albicans isolates were susceptible to TTO, terpinen-4-ol (T-4-ol), and α-terpineol, with an MIC(50) of 0.5, 0.25, and 0.25%, respectively. These three compounds also displayed potent activity against the 69 biofilm-forming strains, of which T-4-ol and α-terpineol displayed rapid kill kinetics. For all three compounds, 1 × MIC(50) effectively inhibited biofilm growth when C. albicans were treated at 0, 1, and 2 h post adhesion. By scanning electron microscopy analysis and PI uptake, TTO and derivative components were shown to be cell membrane active. TTO and T-4-ol were cytotoxic at 1 × MIC(50), whereas at 0.5 × MIC(50) T-4-ol displayed no significant toxicity. Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol. These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms. T-4-ol has safety advantages over the complete essential oil and may be suitable for prophylaxis and treatment of established oropharyngeal candidosis. A clinical trial of T-4-ol is worthy of consideration.

No MeSH data available.


Related in: MedlinePlus

Tea tree oil and T-4-ol are biologically active against mammalian cells. (A) PR fibroblast and OKF6 epithelial cells were grown until 90–100% confluent. These were exposed to 0.5 and 1 × MIC50 of each compound for 2 min. Cell viability was assessed using an XTT assay after incubation in 5% CO2 at 37°C for 2 h. Viability was calculated based on unexposed control cells. For cytokine studies OKF6 cells were grown in 12 well tissue culture trays treated with TTO and T-4-ol at 0.5 × MIC50 for 2 min, washed then stimulated with zymosan (50 μg/ml). Cells were processed for (B) qPCR analysis and (C) supernatant was processed for protein analysis of IL-8. Each assay was performed on three independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.
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Figure 4: Tea tree oil and T-4-ol are biologically active against mammalian cells. (A) PR fibroblast and OKF6 epithelial cells were grown until 90–100% confluent. These were exposed to 0.5 and 1 × MIC50 of each compound for 2 min. Cell viability was assessed using an XTT assay after incubation in 5% CO2 at 37°C for 2 h. Viability was calculated based on unexposed control cells. For cytokine studies OKF6 cells were grown in 12 well tissue culture trays treated with TTO and T-4-ol at 0.5 × MIC50 for 2 min, washed then stimulated with zymosan (50 μg/ml). Cells were processed for (B) qPCR analysis and (C) supernatant was processed for protein analysis of IL-8. Each assay was performed on three independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.

Mentions: The effect of a short exposure (2 min) of TTO and T-4-ol on cellular toxicity was investigated. It was shown that TTO and T-4-ol were toxic to both fibroblast and epithelial cells at 1 × MIC50, reducing the viability of PRF to approximately 12% and OKF6 cells to 35 and 15%, respectively (Figure 4A). At 0.5 × MIC50 T-4-ol displayed no toxicity (98% viable) against PRF compared with TTO (63% viable). Both 0.5× T-4-ol and 0.5× TTO were non-toxic to OKF6 cells (>100% viable).


Antifungal, cytotoxic, and immunomodulatory properties of tea tree oil and its derivative components: potential role in management of oral candidosis in cancer patients.

Ramage G, Milligan S, Lappin DF, Sherry L, Sweeney P, Williams C, Bagg J, Culshaw S - Front Microbiol (2012)

Tea tree oil and T-4-ol are biologically active against mammalian cells. (A) PR fibroblast and OKF6 epithelial cells were grown until 90–100% confluent. These were exposed to 0.5 and 1 × MIC50 of each compound for 2 min. Cell viability was assessed using an XTT assay after incubation in 5% CO2 at 37°C for 2 h. Viability was calculated based on unexposed control cells. For cytokine studies OKF6 cells were grown in 12 well tissue culture trays treated with TTO and T-4-ol at 0.5 × MIC50 for 2 min, washed then stimulated with zymosan (50 μg/ml). Cells were processed for (B) qPCR analysis and (C) supernatant was processed for protein analysis of IL-8. Each assay was performed on three independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376416&req=5

Figure 4: Tea tree oil and T-4-ol are biologically active against mammalian cells. (A) PR fibroblast and OKF6 epithelial cells were grown until 90–100% confluent. These were exposed to 0.5 and 1 × MIC50 of each compound for 2 min. Cell viability was assessed using an XTT assay after incubation in 5% CO2 at 37°C for 2 h. Viability was calculated based on unexposed control cells. For cytokine studies OKF6 cells were grown in 12 well tissue culture trays treated with TTO and T-4-ol at 0.5 × MIC50 for 2 min, washed then stimulated with zymosan (50 μg/ml). Cells were processed for (B) qPCR analysis and (C) supernatant was processed for protein analysis of IL-8. Each assay was performed on three independent occasions in triplicate. *p < 0.05. Error bars represent the ±standard error of the mean.
Mentions: The effect of a short exposure (2 min) of TTO and T-4-ol on cellular toxicity was investigated. It was shown that TTO and T-4-ol were toxic to both fibroblast and epithelial cells at 1 × MIC50, reducing the viability of PRF to approximately 12% and OKF6 cells to 35 and 15%, respectively (Figure 4A). At 0.5 × MIC50 T-4-ol displayed no toxicity (98% viable) against PRF compared with TTO (63% viable). Both 0.5× T-4-ol and 0.5× TTO were non-toxic to OKF6 cells (>100% viable).

Bottom Line: The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation.Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol.These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms.

View Article: PubMed Central - PubMed

Affiliation: Infection and Immunity Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow Glasgow, UK.

ABSTRACT
Candida albicans forms oral biofilms that cause disease and are difficult to treat with conventional antifungal agents. Tea tree oil (TTO) is a natural compound with reported antimicrobial and immunomodulatory activities. The aims of the study were to evaluate the antifungal efficacy of TTO and key derivatives against C. albicans biofilms, to assess the toxicological effects of TTO on a clinically relevant oral cell line, and to investigate its impact on inflammation. TTO and its derivatives were examined against 100 clinical strains of C. albicans. Planktonic minimum inhibitory concentrations (MICs) were determined using the CLSI M-27A broth microdilution method. Sessile MICs were determined using an XTT reduction assay. Inhibition, time-kill, and mode of action studies were performed. OKF6-TERT2 epithelial cells were used for cytotoxicity and cytokine expression assays. Planktonic C. albicans isolates were susceptible to TTO, terpinen-4-ol (T-4-ol), and α-terpineol, with an MIC(50) of 0.5, 0.25, and 0.25%, respectively. These three compounds also displayed potent activity against the 69 biofilm-forming strains, of which T-4-ol and α-terpineol displayed rapid kill kinetics. For all three compounds, 1 × MIC(50) effectively inhibited biofilm growth when C. albicans were treated at 0, 1, and 2 h post adhesion. By scanning electron microscopy analysis and PI uptake, TTO and derivative components were shown to be cell membrane active. TTO and T-4-ol were cytotoxic at 1 × MIC(50), whereas at 0.5 × MIC(50) T-4-ol displayed no significant toxicity. Transcript and protein analysis showed a reduction of IL-8 when treated with TTO and T-4-ol. These data provide further in vitro evidence that TTO and its derivative components, specifically T-4-ol, exhibit strong antimicrobial properties against fungal biofilms. T-4-ol has safety advantages over the complete essential oil and may be suitable for prophylaxis and treatment of established oropharyngeal candidosis. A clinical trial of T-4-ol is worthy of consideration.

No MeSH data available.


Related in: MedlinePlus