by

Bingluo Xu

Melaleuca alternifolia is a plant native to Australia and is used as a traditional medicine in the local area. Tea tree oil (melaleuca oil) is the most well-known product from this plant due to its strong antimicrobial properties on a wide range of bacteria, fungi and other microorganisms. The oil is also used to alleviate the symptoms of irritation caused by infection. It may have some side effects, including inflammation of the mouth, drowsiness, nausea, diarrhoea, and allergy. This review aims to analyse papers on the traditional and modern use, phytochemistry, pharmacology, and efficacy and safety of M. alternifolia, particularly the melaleuca oil.

Introduction

Melaleuca alternifolia (Maiden & Betche) Cheel commonly known as tea tree, belongs to the Myrtaceae (the myrtle family) which includes two subfamilies; the Myrtoideae and the Leptospermoideae. The group of species from the Myrtoideae to which M. alerrnifolia belongs – the Myrtoideae – have fleshy fruits and opposite leaves, like for example the Mediterranean myrtle plant (Myrtus communis L.) commonly found in British gardens. The Leptospermoideae on the other hand bear dry fruits and have either alternate or opposite leaves (Cronquist, 1981).

M. alternifolia is a tall shrub or small tree native to Australia. It is found in the east of Australia, from Queensland to New South Wales. It is an evergreen tall shrub or small tree up to 7m high with papery bark. The hairless leaves are linear and narrow, scattered to whorled and about 10-35mm in length and 1 mm wide. The tree blossoms from spring to early summer, and the flowers are arranged in 3-5 cm long inflorescences which are many-flowered spikes. The individual flowers are white and solitary, each within a bract (a modified leaf with a flower in tis axil). Its petals are usually 2-3mm long, and each bundle contains 30-60 stamens, which are the male part of the flower, and the style is around 3-4mm in length. Fruits are commonly woody and cup-shaped, and are 2-3mm in diameter (Holliday, 2004)

Photograph: structures from Wikimedia Commons and managed by the author

In the last decades, the essential oil from M. alternifolia, called tea tree oil or melaleuca oil, has become a popular dermatological product and an important topic of research. It is a clear, colourless to pale-yellow liquid with a fresh odour (Directory of essential oils for Aromatherapy), and can be extracted from the fresh leaves of M. alternifolia. Tea tree oil is a low-yielding product, and only 1-2% of the mass can be obtained from fresh material (Carson, 1993). The essential oil is widely known as an antiseptic.

Photograph: Tea Tree Oil
http://bewellhub.com/incredible-remedy-to-use-tea-tree-oil-to-promote-hair-growth/

Historical and contemporary uses

Most evidence for traditional uses relates to the indigenous Bundjalung people from the eastern part of Australia. M. alternifolia is used as a traditional medicine in the treatment of coughs and colds by inhaling the oils from the powdered leaves. Tea tree leaves also have a long history as a treatment for cuts and wounds by applying the crushed leaves directly to the injury and covering affected area with mud (Rodney et al., 2015).

Currently, the essential oil of M. alternifolia is widely used in skin products, such as soaps and creams, due to its antiseptic properties. The oil obtained from M. alternifolia is also used as a treatment for bacterial and fungal infection. It is used for relieving the symptoms of various respiratory problems, such as bronchitis. It can also be applied to acne, athlete’s foot, and other external skin infections (World Checklist of Selected Plant Families, 2016). Additionally, tea tree oil is one of the most popular essential oils used in aromatherapy, as it helps to stimulate the immune system and fight against infection.

Phytochemistry

The essential oil of Melaleuca alternifolia is widely used in medicine, cosmetics, and aromatherapy. Tea tree essential oil can be extracted from the fresh leaves of M. alternifolia through steam distillation. The oil is immiscible in water. In 1968, Guenther reported 12 constituents in tea tree oil (Guenther, 1968) and, with the development of chromatography technology, ten years later Swords and Hunter reported 48 components (Swords and Hunter 1978). Another 25 years later, it was suggested that tea tree oil contained more than 100 individual components (Halcon and Milkus, 2004).

Tea tree oil is a mixture of terpinen hydrocarbons, including monoterpenes (C₁₀), sesquiterpenes (C₁₅) and their relative alcohols. Terpinen-4-ol and 1,8-cineole are major compounds in tea tree oil. As tea tree oil is an extremely strong antiseptic, terpinen-4-ol is the main component responsible for its antimicrobial activity. However, 1,8-cineole is considered to have irritant properties on skin and mucous membrane (Carson, 1993). The international quality standard for tea tree oil (terpinen-4-ol type) requires a minimum of 30% terpinen-4-ol and a maximum of 15% of 1,8-cineole (IOS, 2004). Other components like α-terpinene, γ-terpinene, linalool and limonene are also constituents of tea tree oil (Carson, 1995).

Diagram above: structures from Wikimedia Commons and managed by the author

Preclinical data

• Mechanism of antimicrobial action

Most studies on tea tree oil focus on its antimicrobial properties. Cyclic hydrocarbons, such as terpenes, aromatics, and cycloalkanes, are have anti-microbial effects. The lipophilic part of molecule can interact with the lipophilic structures in cells, which is considered to be relevant for the mode of action. The accumulation of lipophilic hydrocarbons in the lipid bilayer membrane of cells affects the structure and function of the cell membrane. Functions of the cell membrane are disrupted by increasing membrane permeability, disrupting homeostasis, and inhibiting cell respiration (Sikkema et al., 1995). Tea tree oil containing cyclic hydrocarbons, like terpinen-4-ol and linalool, are considered to have the same mechanism of action.

• Tea tree oil as an antibacterial agent

The first pharmacological report of tea tree oil was published by Arthur R. Penfold, a chemist who in the 1920s worked for the Australian government. He found that tea tree oil showed strong antiseptic activities twelve times more potent than phenol (Tenny, 1996). The antibacterial properties of tea tree oil against bacteria which have become antibiotic resistant, especially against methicillin-resistant Staphylococcus aureus (MRSA), has attracted increasing interest. Since the first hypothesis of the potential use of tea tree oil against MRSA was reported (Walsh and Longstaff, 1987), the activity of tea tree oil against MRSA has been tested by a number of researchers. Carson (1995), and collaborators, tested 64 MRSA isolates from Australia and the United Kingdom, containing 33 Mupirocin-resistant isolates. The minimum inhibitory concentrations (MICs) were 0.25% for the Australian isolates and 0.312% for the United Kingdom isolates. The minimal bactericidal concentrations (MBCs) for these two strains of bacteria were 0.5% and 0.625%,respectively.

Two studies showed tea tree oil containing terpinen-4-ol and α-terpinene to be effective against Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes. However, cineole was not active against these bacteria. Although I,8-cineole showed limited antibacterial activity, it helped to promote the action of 4-terpinen (Raman et al., 1995, and Gibbons, 2004).

• Tea tree oil as an antifungal agent

Early research focused on the susceptibility of Candida albicans to tea tree oil. Recent data was based on a series of experiments using yeast, dermatophytes and other filamentous fungi which were susceptible to tea tree oil. The tests were performed in different ways and the minimum inhibitory concentrations (the lowest concentration of chemicals that prevents the visible growth of fungus) were found to be between 0.03 and 0.5%. Minimal fungicidal concentrations (the lowest drug dilutions that yield fewer than 3 colonies) ranged from 0.12% to 2%. However, Aspergillus niger should be regarded as an exception; here the minimal fungicidal concentrations was much higher – 8% (Hammer et al., 2002). Nevertheless, these tests were based on fungal conidia, which was impervious to chemical agents. Further data revealed that germinated conidia showed much higher susceptibility to tea tree oil than non-germinated conidia. The intact conidial wall is considered to protect the conidia from tea tree oil (Hammer et al., 2002).

• Tea tree oil as an antiviral agent

Tea tree oil was firstly applied to tobacco plants to examine the antiviral activity. In a field trial, Nicotiana glutinosa L., a relative of the tobacco plant, were sprayed with control solutions of tea tree oil at different concentrations (100, 250 or 500 ppm). The plants were then infected by tobacco mosaic virus for 10 days. The plants treated with control solutions showed significantly more lesions per square centimetre than those treated with tea tree oil (Bishop, 1995).

In a project using human cell culture lines (Schnitzler et al., 2001), different concentrations of melaleuca oil were applied during the incubation of herpes simplex virus (HSV). The treated viruses were then used to infect cell monolayers. Plaques formed after 4-day incubation. The number of plaques was determined and the difference between treated virus and untreated virus (control) group was compared. 50% (relative to controls) plaque formation was inhibited when the virus was treated with 0.0009% tea tree oil. Schnitzler et al. found that adding tea tree oil to the virus at different stages of replication caused a significantly better inhibition of plaque formation. Tea tree oil showed the best effect when added to the free virus.

• Tea tree oil as an antiprotozoal agent

Terpinen-4-ol was reported to be show in vitro effects on the protozoa Leishmania major and Trypanosoma brucei. The concentrations of tea tree oil were 403μg/ml and 0.5μg/ml, respectively (Carson et al., 2005 and Mikus et al.,2000). In a different study, all cells of Trichomonas vaginalis were killed by tea tree oil at the concentration of 300μg/ml (Viollon, 1996).

Clinical evidence

• Acne

A considerable number of clinical trials have evaluated the effects of tea tree oil on relieving the symptoms of acne (Edwards et al. 2015). A study (Bassett, 1990) was designed to assess the efficacy of gel containing 5% tea tree oil compared with gel including the same concentration of benzoyl peroxide in 119 patients. Although benzoyl peroxide helped to reduce more inflamed lesions than tea tree oil did, tea tree oil showed fewer side effects, including scaling, pruritus, and dryness.

• Dental application

In a placebo-controlled study, 40 volunteers were treated with mouthwash containing 0.2% melaleuca oil. Compared with a placebo, tea tree oil helped to reduce the number of mutans streptococci and the total number of oral bacteria after 7 days (Groppo et al., 2002). The reduction lasted for 2 weeks after using the mouthwash containing tea tree oil. In another research, 9 volunteers who had plaques in their mouths were treated by mouthwash containing 0.34% tea tree oil or placebo randomly. It showed no difference in formation and vitality of plaques between the two groups (Arweiler et al., 2000).

• Tinea pedis

The efficacy of tea tree oil in improving foot problems has been assessed in a randomised, double blind by applying cream containing 10% (w/w) tea tree oil, 1% tolnaftate or placebo including 104 patients with tinea pedis caused by fungi. After 4 weeks of daily treatment, 30%, 85%, and 21% of patients who applied cream with tea tree oil, tolnaftate and placebo, respectively, showed a negative culture (i.e. successful treatment). Compared with the placebo group, tea tree oil and tolnaftate helped to relieve symptoms including scaling, inflammation, and itching. Although tea tree oil showed better results in the improvement of symptoms than the placebo, there was still no difference in mycological treatment (Tong et al., 1992).

Toxicology

• Oral toxicity

When taken orally, tea tree oil may cause inflammation of the mouth, drowsiness, nausea, and diarrhoea (Kumari, 2013). The ingestion of a certain amount of tea tree oil leads to muscular tremors, respiratory distress, and even coma. The oral LD₅₀ for tea tree oil in rats is 1.9g/kg (Russell, 1999). As tea tree oil is toxic orally, mouthwash containing the oil should be used carefully. Pregnant or breastfeeding women should use tea tree oil preparation cautiously. Children who need to use tea tree oil should do so under the supervision of parents.

• Dermal toxicity

In a study, 217 patients were tested with 10% tea tree oil patches, and no irritant or allergic reactions were reported (Veien, 2004). Recent evidence showed that tea tree oil is able to cause allergic reactions in individuals who have a sensitive skin. Before using tea tree oil products it is recommended that susceptible individuals have a skin test. As tea tree oil may cause irritant and allergic reactions when applied on skin, using high concentrations of oil should be avoided.

Conclusion

Melaleuca alternifolia has been used for centuries. Instead of the traditional use of leaves, it is more famous for its distilled essential oil which has been widely used due to its antimicrobial activity. Researches are mainly based on the antimicrobial property of melaleuca oil. Only a few studies involve other usage of tea tree oil and other parts of this plant. It is generally considered to be safe for topical used if used according to the general guidelines, but care must be taken especially with respect to possible allergic effects. And with all essential oils (or any other substance used medicinally) the recommended doses should not be exceeded Tea tree oil is not recommended for medical and therapeutic uses. The oil is widely applied in cosmetic products for its antiseptic properties. There are two THR products containing tea tree oil in UK market which are used to relieve minor skin conditions including spots, pimples and itching based on traditional use only. As it helps people to achieve better skin conditions, it would be excellent if more cosmetic or THR products containing Melaleuca oil come onto the UK market.

DISCLAIMER

In this essay, we do not intend to advise or recommend herbs for medicinal or health use. This information is for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflets (i.e. for THR products). The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

© Bingluo Xu, MSc student (2016 – 2017),

Research Cluster ‘Biodiversity and Medicines’ / Centre for Pharmacognosy and Phytotherapy
UCL School of Pharmacy, Univ. London
29 – 39 Brunswick Sq.
London WC1N 1AX

Reference

Arweiler, N.B., Donos, N., Netuschil, L., Reich, E. and Sculean, A., 2000. Clinical and antibacterial effect of tea tree oil–a pilot study. Clinical oral investigations, 4(2), pp.70-73.

Bassett, I.B., Pannowitz, D.L. and Barnetson, R.S., 1990. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. The Medical Journal of Australia, 153(8), pp.455-458.

Bishop, C.D., 1995. Antiviral activity of the essential oil of Melaleuca alternifolia (Maiden amp; Betche) Cheel (tea tree) against Tobacco Mosaic Virus. Journal of Essential Oil Research, 7(6), pp.641-644.

Carson, C.F. and Riley, T.V., 1993. Antimicrobial activity of the essential oil of Melaleuca alternifolia. Letters in Applied Microbiology, 16(2), pp.49-55.

Carson, C.F. and Riley, T.V., 1995. Antimicrobial activity of the major components of the essential oil of Melaleuca alternifolia. Journal of applied bacteriology, 78(3), pp.264-269.

Carson, C.F., Cookson, B.D., Farrelly, H.D. and Riley, T.V., 1995. Susceptibility of methicillin-resistant Staphylococcus aureus to the essential oil of Melaleuca alternifolia. Journal of Antimicrobial Chemotherapy, 35(3), pp.421-424.

Carson, C.F., Riley, T.V. and Hammer, K.A., 2005. Compilation and Review of Published and Unpublished Tea Tree Oil Literature: A Report for the Rural Industries Research and Development Corporation. Rural Industries Research and Development Corporation.

Cronquist, A., 1981. An integrated system of classification of flowering plants. Columbia University Press.

Edwards, S., I. da Costa-Rocha, E.M. Williamson and M. Heinrich 2015 Phytopharmacy – an evidence-based guide to herbal medicines. Wiley, Chichester.

Gibbons, S., 2004. Anti-staphylococcal plant natural products. Natural product reports, 21(2), pp.263-277.

Groppo, F.C., Ramacciato, J.C., Simoes, R.P., Florio, F.M. and Sartoratto, A., 2002. Antimicrobial activity of garlic, tea tree oil, and chlorhexidine against oral microorganisms. International dental journal, 52(6), pp.433-437.

Halcón, L. and Milkus, K., 2004. Staphylococcus aureus and wounds: a review of tea tree oil as a promising antimicrobial. American Journal of Infection Control, 32(7), pp.402-408.

Hammer, K.A., Carson, C.F. and Riley, T.V., 2002. In vitro activity of Melaleuca alternifolia (tea tree) oil against dermatophytes and other filamentous fungi. Journal of Antimicrobial Chemotherapy, 50(2), pp.195-199.

Holistic-online.com, 2017. Aromatherapy, Tea tree oil, Australian tea tree oil, Melaleuca alternifolia, Ti tree oil, Essential Oils,Holisticonline.com. [online] Available at: http://www.holistic-online.com/Aromatherapy/aroma_ess-oil-tea-tree-oil.htm [Accessed 18 Mar. 2017].

Holliday, I., 2004. Melaleucas: a Field and Garden Guide, 2nd edition. Reed New Holland, Sydney.

Kumari, P., 2013. Antimicrobial properties of tea tree oil. International Journal of Bioinformatics and Biological Sciences, 1(1), p.71-77.

Mikus, J., Harkenthal, M., Steverding, D. and Reichling, J., 2000. In vitro effect of essential oils and isolated mono-and sesquiterpenes on Leishmania major and Trypanosoma brucei. Planta Medica, 66(04), pp.366-368.

Raman, A., Weir, U. and Bloomfield, S.F., 1995. Antimicrobial effects of tea‐tree oil and its major components on Staphylococcus aureus, Staph. epidermidis and Propionibacterium acnes. Letters in Applied Microbiology, 21(4), pp.242-245.

Jammy, R., Japar, S. and Shah, M.K.M., 2015. Review: Tea Tree (Melaleuca alternifolia) As A New Material For Biocomposites. Journal of Applied Science & Agriculture, 10(3), pp.21-39.

Russell, M., 1999. Toxicology of tea tree oil, p. 191-201. In I. Southwell and R. Lowe (ed.), Tea tree: the genus Melaleuca, vol. 9. Harwood Academic Publishers, Amsterdam, The Netherlands.

Schnitzler, P., Schön, K. and Reichling, J., 2001. Antiviral activity of Australian tea tree oil and eucalyptus oil against herpes simplex virus in cell culture. Die Pharmazie, 56(4), pp.343-347.

Sikkema, J., De Bont, J.A. and Poolman, B., 1995. Mechanisms of membrane toxicity of hydrocarbons. Microbiological reviews, 59(2), pp.201-222.

Swords, G. and Hunter, G.L.K., 1978. Composition of Australian tea tree oil (Melaleuca alternifolia). Journal of Agricultural and Food Chemistry, 26(3), pp.734-737.

Tenny, D.,1996. Woodland Health Series Tea Tree Oil. Woodland Publishing.

Tong, M.M., Altman, P.M. and Barnetson, R.S., 1992. Tea tree oil in the treatment of tinea pedis. Australasian Journal of Dermatology, 33(3), pp.145-149.

Veien, N.K., Rosner, K. and Skovgaard, G.L., 2004. Is tea tree oil an important contact allergen?. Contact dermatitis, 50(6), pp.378-379.

Viollon, C., Mandin, D. and Chaumont, J.P., 1996. Activities antagonistes, in vitro, de quelques huiles essentielles et de composes naturels volatils viv a vis de la croissance de Trichomonas vaginalis. Fitoterapia, 63, pp.279-281.

Walsh, L.J. and Longstaff, J., 1987. The antimicrobial effects of an essential oil on selected oral pathogens. Periodontology, 8, pp.11-15.

World Checklist of Selected Plant Families, 2016. Melaleuca alternifolia (Maiden & Betche) Cheel. Published on the internet by the Board of Trustees of the Royal Botanic Gardens, Kew.