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Tea Tree Oil (Melaleuca alternifolia)


Melaleuca alternifolia
Synonyms / Common Names / Related Terms
Alpha-terpineol, Australian tea tree oil, Bogaskin® (veterinary formulation), breathaway, Burnaid®, cymene, gamma-terpinen, malaleuca, Melaleuca alternifolia, Melaleuca alternifolia Cheel, Melaleuca alternifolia Hydrogel® (burn dressing), melaleuca oil, melaleucae, oil of mela-leuca, oleum, Oleum melaleucae, T36-C7, Tebodont®, teebaum, terpinen, terpinen-4-ol, terpinenol-4, ti tree, TTO.

Note: Tea tree oil should not be confused with cajeput oil, niauouli oil, kanuka oil, or manuka oil obtained from other Melaleuca species.




Mechanism of Action

Pharmacology:

  • The tea tree is related to Melaleuca quinquenervia and Melaleuca cajuputi (trees that produce oils commonly used in aromatherapy, similar to camphor and peppermint). However, tea tree oil comes exclusively from Melaleuca alternifolia and should not be confused with cajeput oil, niauouli oil, kanuka oil, or manuka oil obtained from other Melaleuca species. Their composition is quite different and these other species contain higher concentrations of cineole, a skin irritant that may decrease the antiseptic activity of the purported active ingredient of tea tree oil (terpinen-4-ol).
  • Constituents: Constituents of tea tree oil include 1,8-cineole, terpinen-4-ol, alpha-terpineol, and gamma-terpinen.28,21,22,23
  • Anticancer effects: Tea tree oil interacts preferentially with the less ordered DPPC "sea" and does not alter the more ordered lipid "rafts." Tea tree oil was found to interact with multi-drug resistant (MDR) melanoma cell plasma membrane. Tea tree oil was not found to interfere with the function of the MDR drug transporter P-gp. It has been proposed that the effect exerted on MDR melanoma cells is mediated by the interaction with the fluid DPPC phase, rather than with the more organized "rafts." This interaction preferentially influences the ATP-independent antiapoptotic activity of P-gp likely localized outside "rafts".26
  • Antifungal effects: The antimycotic properties of tea tree oil and of terpinen-4-ol, gamma-terpinen, and 1,8-cineole were evaluated in vitro on Fusarium graminearum, Fusarium culmorum, and Pyrenophora graminea. All the tested fungi were susceptible to tea tree oil and its components.23 Tea tree oil has also been shown to be active against Madurella mycetomatis and Trichophyton mentagrophytes.6,20,18 In one study, 301 yeasts isolated from the mouths of 199 patients suffering from advanced cancer were examined by an in vitro agar dilution assay for susceptibility to tea tree oil. All of the isolates tested were susceptible, including 41 that were known to be resistant to both fluconazole and itraconazole.5 The in vitro and in vivo anti-Candida activity of two constituents of tea tree oil, terpinen-4-ol and 1,8-cineole, was investigated. Fungicidal concentrations of terpinen-4-ol were equivalent to the candidastatic activity. In the rat vaginal infection model, terpinen-4-ol was as active as tea tree oil in accelerating clearance from the vagina of all Candida strains examined.21 At a concentration of 0.2mg/mL, Leptospermum petersonii oil, an oil of tea tree, was more than 90% effective against all of the dermatophytes (Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, Epidermophyton floccosum, and Microsporum gypseum) tested, with the exception of T. rubrum.7 Tea tree oil was found to inhibit the growth of wild-type and slg1/wsc1 mutant cells at a threshold of approximately 0.1% v/v, with the purified compounds acting already at half these concentrations. A mid2 deletion displayed hyper-resistance. Tea tree oil also induced the signaling pathway in a dose-dependent manner.22 Furthermore, dandruff may be related to the yeast, Pityrosporum ovale. Tea tree oil has antifungal properties against P. ovale and therefore, may be useful in the treatment of dandruff.19
  • Anti-inflammatory effects: Hart et al. have found that tea tree oil suppresses the production of tumor necrosis factor-alpha, interleukin-1β, interleukin-10, and prostaglandin E2 by activated monocytes in vitro .25 Budhiraja et al. found that tea tree oil induces differentiation of myelocytes into monocytes in vitro.24 Tea tree oil suppresses the production of superoxide by activated monocytes in vitro.1 Terpinen-4-ol has been isolated by gas chromatography to be the most likely active anti-inflammatory constituent of tea tree oil in vitro .25 Furthermore, sessions of tea tree oil inhalation in mice were found to exert a strong anti-inflammatory influence on the immune system stimulated by Zymosan injection, while having no influence on peritoneal leukocytes (PTL) number, reactive oxygen species (ROS) level, and cyclooxygenase (COX) activity in mice without inflammation.4 The hypothalamic-pituitary-adrenal (HPA) axis was shown to mediate the anti-inflammatory effect of tea tree oil. Antalarmin abolished the influence of inhaled tea tree oil on PTL number and their ROS production in mice with experimental peritonitis, but it had no effect on these parameters in mice without inflammation.
  • Antimicrobial effects: Multiple studies have reported the antimicrobial effects of tea tree oil.8,2,3,9,4,11,12,13,14,15,16,17,18 Tea tree oil has been found to stimulate autolysis of bacterial cells in both the exponential and stationary growth phases, with greater activity during the exponential phase.29 In vitro studies conducted by Cox et al. found that at concentrations that inhibit the growth of several bacterial species, tea tree oil also inhibited glucose-stimulated leakage of intracellular potassium.30,31 single in vitro study reported that the antibacterial activity of tea tree oil is decreased by the presence of organic matter or the surfactants Tween 20 and Tween 80.10 Tea tree oil inhibits the in vitro conversion of Candida albicans from yeast to mycelial form.32 Through in vitro studies of the antimicrobial activity of tea tree oil, it has been demonstrated that terpinen-4-ol is the component most likely responsible for its antimicrobial properties.33 Tea tree oil was also found to exert a greater bactericidal activity against biofilm-grown (meticillin-resistant Staphylococcus aureus) MRSA and (meticillin-sensitive Staphylococcus aureus) MSSA isolates than against some biofilm-grown (coagulase-negative staphylococci) CoNS isolates.34
  • Dental effects: Periodontopathic bacterial strains tested, including Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sobrinus, were completely killed by 30s of exposure to tea tree oil. Tea tree oil showed significant adhesion-inhibiting activity against P. gingivalis.17
  • Insecticidal effects: Tea tree oil has been shown to inhibit acetylcholinesterase that may, in turn, contribute to its insecticidal activity.28 Different species of insects are susceptible to different essential oil components. The relative acaricidal and pediculicidal activity of tea tree oil were evaluated. Tea tree oil was found to be the most effective against both lice and mites compared to and lemon oil.23

Pharmacodynamics/Kinetics:

  • Absorption: Tea tree oil was found to decrease the skin integrity dose-dependently.35 A small quantity of tea tree oil components, 1.1-1.9% and 2-4% of the applied amount following application of a 20% tea tree oil solution and pure TTO, respectively, penetrated into or through human epidermis. The largest tea tree oil component that penetrated the skin was terpinen-4-ol. Following the partial occlusion of the application site, the penetration of terpinen-4-ol increased to approximately 7% of the applied tea tree oil. Measurement of the rate of evaporation of tea tree oil from filter paper (7.4mg/cm2) showed that 98% of the oil evaporated in four hours.36 One percent tea tree oil did not affect barrier conditions in an experimental in vitro model using static diffusion cells with human skin. The Kp value for tritiated water was increased significantly at 5% tea tree oil, which demonstrated that the barrier integrity is affected at this relatively low concentration of tea tree oil. Although the barrier integrity was not seriously damaged, the data indicated an initiated and concentration-dependent effect on the barrier integrity.37
  • The flux values of three different semisolid preparations with 5% tea tree oil showed the rank order semisolid O/W emulsion (0.067mcL/cm2 h) > white petrolatum (0.051mcL/cm2 h) > ambiphilic cream (0.022mcL/cm2 h). Compared to the flux value obtained with the native tea tree oil (0.26 mcL/cm2 h), the flux values are remarkably reduced due to the lower amount of terpinen-4-ol. P(app) values for cream (2.74 ± 0.06 x 10(-7) cm/s) and native tea tree oil (1.62 ± 0.12 x 10(-7) cm/s) are comparable, while white petrolatum (6.36 ± 0.21 x 10(-7) cm/s) and semisolid O/W emulsion (8.41 ± 0.15 x 10(-7) cm/s) demonstrated higher values indicating a penetration enhancement. No relationship between permeation and liberation was found.38
  • Median inhibition concentration: 1,8-cineole and terpinen-4-ol were shown to inhibit acetylcholinesterase at IC50 values of 0.04 and 10.30mM, respectively. Four samples of tea tree oil tested (Tisserand, Body Treats, Main Camp and Irish Health Culture Association Pure Undiluted) showed anticholinesterase activity at IC50 values of 0.05, 0.10, 0.08, and 0.11mcL mL(-1), respectively.28
  • Minimal inhibitory concentrations: In vitro minimal inhibitory concentrations (MIC90) values were to be 0.06% (v/v) for terpinen-4-ol and 4% (v/v) for 1,8-cineole, two constituents of tea tree oil, regardless of susceptibility or resistance of the strains to fluconazole and itraconazole.21 Fungicidal concentrations of terpinen-4-ol were equivalent to the candidastatic activity. In a rat vaginal infection model, terpinen-4-ol was as active as tea tree oil in accelerating clearance from the vagina of all candida strains examined.21
  • The MIC90 of tea tree oil for 30 isolates of Pseudomonas aeruginosa, 15 isolates of Pseudomonas putida, and 11 isolates of Pseudomonas fluorescens was 4% (v/v) or less.39 Susceptibility to the components tested varied between species.
  • The hyphal growth of Microsporum gypseum and Trichophyton rubrum was not inhibited at concentrations of 0.05mg/mL and 0.1 mg/mL by Leptospermum petersonii oil, an oil of tea tree. The antifungal activities of Leptospermum petersonii oil against Trichophyton mentagrophytes and Microsporum canis were 39% and 20%, respectively, at a concentration of 0.1mg/mL. The antifungal activities of Leptospermum petersonii oil increased considerably when the concentration was increased to 0.15mg/mL.7
  • MIC50 of tea tree oil against MRSA was found to be 1,024mg/L (512-2,048).27

References
  1. Brand, C., Ferrante, A., Prager, R. H., Riley, T. V., Carson, C. F., Finlay-Jones, J. J., and Hart, P. H. The water-soluble components of the essential oil of Melaleuca alternifolia (tea tree oil) suppress the production of superoxide by human monocytes, but not neutrophils, activated in vitro. Inflamm Res 2001;50(4):213-219. 11392609
  2. Caldefie-Chezet, F., Guerry, M., Chalchat, J. C., Fusillier, C., Vasson, M. P., and Guillot, J. Anti-inflammatory effects of Melaleuca alternifolia essential oil on human polymorphonuclear neutrophils and monocytes. Free Radic Res 2004;38(8):805-811. 15493453
  3. Carson, C. F., Hammer, K. A., and Riley, T. V. Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev 2006;19(1):50-62. 16418522
  4. Golab, M. and Skwarlo-Sonta, K. Mechanisms involved in the anti-inflammatory action of inhaled tea tree oil in mice. Exp Biol Med (Maywood) 2007;232(3):420-426. 17327476
  5. Bagg, J., Jackson, M. S., Petrina, Sweeney M., Ramage, G., and Davies, A. N. Susceptibility to Melaleuca alternifolia (tea tree) oil of yeasts isolated from the mouths of patients with advanced cancer. Oral Oncol 2006;42(5):487-492. 16488180
  6. Inouye, S., Uchida, K., Nishiyama, Y., Hasumi, Y., Yamaguchi, H., and Abe, S. Combined effect of heat, essential oils and salt on fungicidal activity against Trichophyton mentagrophytes in a foot bath. Nippon Ishinkin Gakkai Zasshi 2007;48(1):27-36. 17287720
  7. Park, M. J., Gwak, K. S., Yang, I., Choi, W. S., Jo, H. J., Chang, J. W., Jeung, E. B., and Choi, I. G. Antifungal activities of the essential oils in Syzygium aromaticum (L.) Merr. Et Perry and Leptospermum petersonii Bailey and their constituents against various dermatophytes.
    J Microbiol 2007;45(5):460-465. 17978807
  8. Belaiche P. Treatment of skin infections with the essential oil of Melaleuca alternifolia. Phytotherapy 1985;15:15, 17.
  9. Crawford, G. H., Sciacca, J. R., and James, W. D. Tea tree oil: cutaneous effects of the extracted oil of Melaleuca alternifolia. Dermatitis 2004;15(2):59-66. 15473330
  10. Hammer, K. A., Carson, C. F., and Riley, T. V. Influence of organic matter, cations and surfactants on the antimicrobial activity of Melaleuca alternifolia (tea tree) oil in vitro. J Appl Microbiol 1999;86(3):446-452. 10196749
  11. Kulik, E., Lenkeit, K., and Meyer, J. [Antimicrobial effects of tea tree oil (Melaleuca alternifolia) on oral microorganisms]. Schweiz Monatsschr Zahnmed 2000;110(11):125-130. 11374358
  12. May, J., Chan, C. H., King, A., Williams, L., and French, G. L. Time-kill studies of tea tree oils on clinical isolates. J Antimicrob Chemother 2000;45(5):639-643. 10797086
  13. McMahon, M. A., Blair, I. S., Moore, J. E., and McDowell, D. A. Habituation to sub-lethal concentrations of tea tree oil (Melaleuca alternifolia) is associated with reduced susceptibility to antibiotics in human pathogens. J Antimicrob Chemother 2007;59(1):125-127. 17071952
  14. Messager, S., Hammer, K. A., Carson, C. F., and Riley, T. V. Effectiveness of hand-cleansing formulations containing tea tree oil assessed ex vivo on human skin and in vivo with volunteers using European standard EN 1499. J Hosp Infect 2005;59(3):220-228. 15694979
  15. Schelz, Z., Molnar, J., and Hohmann, J. Antimicrobial and antiplasmid activities of essential oils. Fitoterapia 2006;77(4):279-285. 16690225
  16. Shapiro, S., Meier, A., and Guggenheim, B. The antimicrobial activity of essential oils and essential oil components towards oral bacteria. Oral Microbiol Immunol 1994;9(4):202-208. 7478759
  17. Takarada, K., Kimizuka, R., Takahashi, N., Honma, K., Okuda, K., and Kato, T. A comparison of the antibacterial efficacies of essential oils against oral pathogens. Oral Microbiol Immunol 2004;19(1):61-64. 14678476
  18. van de Sande, W. W., Fahal, A. H., Riley, T. V., Verbrugh, H., and van Belkum, A. In vitro susceptibility of Madurella mycetomatis, prime agent of Madura foot, to tea tree oil and artemisinin. J Antimicrob Chemother 2007;59(3):553-555. 17324961
  19. Satchell, A. C., Saurajen, A., Bell, C., and Barnetson, R. S. Treatment of dandruff with 5% tea tree oil shampoo. J Am Acad Dermatol 2002;47(6):852-855. 12451368
  20. Inouye, S., Nishiyama, Y., Uchida, K., Hasumi, Y., Yamaguchi, H., and Abe, S. The vapor activity of oregano, perilla, tea tree, lavender, clove, and geranium oils against a Trichophyton mentagrophytes in a closed box. J Infect Chemother 2006;12(6):349-354. 17235639
  21. Mondello, F., De Bernardis, F., Girolamo, A., Salvatore, G., and Cassone, A. In vitro and in vivo activity of tea tree oil against azole-susceptible and -resistant human pathogenic yeasts. J Antimicrob Chemother 2003;51(5):1223-1229. 12668571
  22. Straede, A., Corran, A., Bundy, J., and Heinisch, J. J. The effect of tea tree oil and antifungal agents on a reporter for yeast cell integrity signalling. Yeast 2007;24(4):321-334. 17397109
  23. Williamson, E. M., Priestley, C. M., and Burgess, I. F. An investigation and comparison of the bioactivity of selected essential oils on human lice and house dust mites. Fitoterapia 2007;78(7-8):521-525. 17662541
  24. Budhiraja, S. S., Cullum, M. E., Sioutis, S. S., Evangelista, L., and Habanova, S. T. Biological activity of Melaleuca alternifola (Tea Tree) oil component, terpinen-4-ol, in human myelocytic cell line HL-60. J Manipulative Physiol Ther 1999;22(7):447-453. 10519561
  25. Hart, P. H., Brand, C., Carson, C. F., Riley, T. V., Prager, R. H., and Finlay-Jones, J. J. Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res 2000;49(11):619-626. 11131302
  26. Giordani, C., Molinari, A., Toccacieli, L., Calcabrini, A., Stringaro, A., Chistolini, P., Arancia, G., and Diociaiuti, M. Interaction of tea tree oil with model and cellular membranes. J Med Chem 7-27-2006;49(15):4581-4588. 16854063
  27. LaPlante, K. L. In vitro activity of lysostaphin, mupirocin, and tea tree oil against clinical methicillin-resistant Staphylococcus aureus.
    Diagn Microbiol Infect Dis 2007;57(4):413-418. 17141452
  28. Mills, C., Cleary, B. J., Gilmer, J. F., and Walsh, J. J. Inhibition of acetylcholinesterase by Tea Tree oil. J Pharm Pharmacol 2004;56(3):375-379. 15025863
  29. Gustafson, J. E., Liew, Y. C., Chew, S., Markham, J., Bell, H. C., Wyllie, S. G., and Warmington, J. R. Effects of tea tree oil on Escherichia coli. Lett Appl Microbiol 1998;26(3):194-198. 9569708
  30. Cox, S. D., Gustafson, J. E., Mann, C. M., Markham, J. L., Liew, Y. C., Hartland, R. P., Bell, H. C., Warmington, J. R., and Wyllie, S. G. Tea tree oil causes K+ leakage and inhibits respiration in Escherichia coli. Lett Appl Microbiol 1998;26(5):355-358. 9674165
  31. Cox, S. D., Mann, C. M., Markham, J. L., Bell, H. C., Gustafson, J. E., Warmington, J. R., and Wyllie, S. G. The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil). J Appl Microbiol 2000;88(1):170-175. 10735256
  32. D'Auria, F. D., Laino, L., Strippoli, V., Tecca, M., Salvatore, G., Battinelli, L., and Mazzanti, G. In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. J Chemother 2001;13(4):377-383. 11589479
  33. Carson, C. F. and Riley, T. V. Antimicrobial activity of the major components of the essential oil of Melaleuca alternifolia. J Appl Bacteriol 1995;78(3):264-269. 7730203
  34. Brady, A., Loughlin, R., Gilpin, D., Kearney, P., and Tunney, M. In vitro activity of tea-tree oil against clinical skin isolates of meticillin-resistant and -sensitive Staphylococcus aureus and coagulase-negative staphylococci growing planktonically and as biofilms. J Med Microbiol 2006;55(Pt 10):1375-1380. 17005786
  35. Nielsen, J. B. Natural oils affect the human skin integrity and the percutaneous penetration of benzoic acid dose-dependently. Basic Clin Pharmacol Toxicol 2006;98(6):575-581. 16700820
  36. Cross, S. E., Russell, M., Southwell, I., and Roberts, M. S. Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro. Eur J Pharm Biopharm 2008;69(1):214-222. 17983738
  37. Nielsen, J. B. and Nielsen, F. Topical use of tea tree oil reduces the dermal absorption of benzoic acid and methiocarb. Arch Dermatol Res 2006;297(9):395-402. 16315066
  38. Reichling, J., Landvatter, U., Wagner, H., Kostka, K. H., and Schaefer, U. F. In vitro studies on release and human skin permeation of Australian tea tree oil (TTO) from topical formulations. Eur J Pharm Biopharm 2006;64(2):222-228. 16846726
  39. Papadopoulos, C. J., Carson, C. F., Hammer, K. A., and Riley, T. V. Susceptibility of pseudomonads to Melaleuca alternifolia (tea tree) oil and components. J Antimicrob Chemother 2006;58(2):449-451. 16735435




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