Scientific Name
Melaleuca alternifolia (Maiden & Betche) Cheel
Synonyms
Melaleuca linariifolia var. alternifolia Maiden & Betche[1]
Vernacular Name
Geographical Distributions
Melaleuca alternifolia is a perennial plant, native to Australia. It grows wild on sandy soils in New South Wales. In Malaysia, it was first cultivated in Perlis and Kedah in 1993. [2]
Botanical Description
M. alternifolia is a hardwood tree of the Myrtaceae family. It is a narrow-leaved tree 6-7m tall. The bark is layered and papery. The entire plant is glabrous.
The leaves are alternate, aromatic and 10-35 mm long, about 1 mm wide. The petiole is 1 mm long.
The inflorescences are many-flowered spikes, 3-5 cm long, with axes bearing short hairs. The white flowers are solitary and petals are 2-3 mm long. The flowersare scattered in an interrupted spike. The stamens are 30-60 in number and more than 12 mm long, united at their bases to form 5 distinct bundles.
The capsule persists within the fruiting hypanthium. The fruits are spaced sparsely along the branches. The fruit has many seeded, cup shaped and 2-3mm in diameter. A hole of 1.5-2.5 mm diameter is present which enables the release and dispersal of seeds by wind. [4][5][6][7]
Cultivation
Soil Suitability and Climate Requirement
M. alternifolia grows well on tropical soils with good drainage, fertile, with 18-31.4 oC temperature and 1200-1600 mm annual rainfall. Crops planted on fertile soils will grow faster and produce bigger canopy. [2]
Field Preparation
Land Preparation
Normal operation such as land clearing, disc ploughing and rotovation have to be conducted before planting. Field drainage system has to be established in areas that are easily waterlogged. [2]
Production of Planting Materials
M. alternifolia is propagated by seeds. Seeds at the rate of 0.5 g/m2 are sown in sowing trays or beds. The use of pathogen free or sterilised sowing media is strongly recommended. The seeds germinate after 7-10 days and subsequently at 5 to 7-leaf stage the seedlings are transferred into polybags (10 cm x 15 cm). Fungicide is sprayed regularly to control damping-off disease. The seedlings are ready for field planting after 3 months in polybags. [2]
Field Planting
For a two-row avenue planting, the seedlings are planted at 0.6 m (between rows) x 0.4 m (within a row) with 1.5 m avenue width which will give a population density of 23,810 plants/ha. Large scale planting can be mechanised and in areas where flash flood is pertinent, it can be planted on raised beds. [2]
Field maintenance
Fertilisation
The rate of fertiliser depends on soil types. For clay loan soil, fertiliser (N:P2O5:K2O) at the rate of 200:50:70 kg/ha is recommended. Whereas for sandy bris soil, 10 t/ha chicken manure and 240:240:340 kg/ha of N:P2O5:K2O are recommended. Fertilisers such as NPK (15:15:15) or NPK (12:12:17:2) can be used but the amount has to be equally divided and applied within 1st, 3rd, 5th and 7th month of planting. The same rate of fertiliser is repeated for the ratoon crops. [2] [8-9]
Weed Control
Weed problem can be controlled by spraying pre-emergence herbicide at planting. Later, weed control is done by spraying contact herbicide or by using grass-cutter. [2]
Water management
Sprinkler or rain-gun irrigation system is recommended for this crop. Supplementary irrigation is critical particularly at the early crop establishment stage. [2]
Pest and Disease Control
So far, there is no serious pest and disease observed for this crop. Nonetheless, termites need to be looked for as it may cause some damages to the plants in the field. [2]
Harvesting
M. alternifolia can be harvested 7-12 months after planting, depending on crop growth. Harvesting is done by cutting the plants at 15-30 cm above ground. On clay loam soil, the biomass yields is 20 t/ha or equivalent to 150-200 kg/ha essential oil with 0.7-1.0% oil recovery. Whereas on sandy bris oil, the biomass yield is 12.5-17.3 t/ha or equivalent to 115-136 L/ha essential oil with 0.78-0.92% (vol/wt) oil recovery. After harvesting, the plants will produce new shoots which will develop into new foliage that can be harvested again after 6 months. This practice can be repeated further whereby a good crop is expected to be economically productive for 10 years. On clay loan soil, the biomass yields of first and second ratoon are 25 and 30 t/ha respectively. [2] [8-10]
Postharvest handling
The harvested biomass need to be immediately brought to collection centre, chopped into smaller pieces and loaded into distiller. The oil distillation process will take about 3 hours. [2]
Estimated cost of production
The production cost for one hectare crop is estimated at RM18,700, RM15,600 and RM15,500 respectively for the 1st, 2nd and 3rd year onwards. Thus, at the yield levels of 20, 25 and 30 t/ha the production cost per kilogramme biomass are RM0.90, RM0.60 and RM0.50 respectively. Similarly, the production cost of a kilogramme of essential oil is RM83-RM111 for oil yield of 120-200 kg. The production cost was estimated based on the cost of current inputs during writing of this article. [2]
Chemical Constituent
M. alternifolia has been rported to contain terpinen-4-ol (29-45%), γ-terpinene (10-28%), α-terpinene (2.7-13.0%) and 1,8-cineole (4.5-16.5%). Other mono-terpenes present in significant quantities (1-5%) include α-pinene, limonene, p-cymene and terpinolene. [6][11][12][13]
Plant Part Used
Leaves [6]
Traditional Use
Bundjalung Aborigines of New South Wales inhaled vapours from crushed tea tree leaves by applying a poultice made of tea tree leaves to treat coughs, colds, insect bites, abrasions, and skin infections [14]. It is used as an antiseptic and disinfectant for wounds and heals burns. It is also effective for the treatment of dandruff and scalp problems. Lastly, it can be used for treatment of bleeding gums, gingivitis and periodontal disease [15].
Preclinical Data
Pharmacology
Cytotoxic activity
The potential anti-tumoral activity of M. alternifolia was analysed against human melanoma cells and their drug-resistant counterparts. It was concluded that tea tree oil and terpinen-4-ol are able to inhibit the growth of human melanoma cells and are more effective on their resistant variants by inducing caspase-dependent apoptosis of melanoma cells. [16]
In was also reported that M. alternifolia and its major active terpene component terpinen-4-ol significantly inhibit the growth of two murine tumour cell lines (AE17 mesothelioma and B16 melanoma) in a dose and time-dependent manner. It induced necrotic cell death coupled with low level apoptotic cell death in both tumour cell lines. However, it does not seem to affect non-tumour fibroblast cells. [17]
Antioxidant and anti-inflammatory activity
Studies found that the essential oil of M. alternifolia at a concentration of 0.1% directly stimulated reactive oxygen species (ROS) production by polymorphonuclear neutrophils (PMNs) (x8.7 vs. 0% EO, p<0.05) and increased the intracellular ROS produced by monocytes. Regardless of the stimulating agent used (a phorbol ester, formyl-methionyl-leucyl-phenylalanine or opsonised zymosan), the tea tree oil decreased the intracellular ROS production at the dilution of 0.1% by PMNs and monocytes, more so with PMNs. This shows that M. alternifolia also protects organism from an excess of ROS through an antioxidant and radical scavenging activity apart from being a direct active mediator of bactericidal action of circulating leucocytes. [18]
M. alternifolia essential oil does not only act as an anti-inflammatory mediator through its antioxidant activity but also protects the organism by reducing the proliferation of inflammatory cells without affecting their capacity to secrete anti-inflammatory cytokines. [19]
Study reported that the water soluble component of M. alternifolia significantly suppressed the agonist-stimulated superoxide production by monocytes. The water soluble components were analysed as terpinen-4-ol, alpha-terpineol and 1,8-cineole whereit was found that only alpha-terpineol could significantly suppress N-formyl-methionyl-leucyl-phenylalanine- (fMLP), lipopolysaccharide- (LPS) and phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide production. [20]
Acaricidal activity
Comparison was made for the acaricidal activity between M. alternifolia oil and some of its individual active components on the itch mite Sarcoptes scabiei var hominis. The results suggested that the terpinen-4-ol is the primary active component which has its potential role to be a new topical acaricide. [21]
In the study where two major constituents of tea tree oil, 1,8-cineole and terpinen-4-ol, were shown to inhibit acetylcholinesterase at IC50 values (inhibitor concentrations required to give 50% inhibition) of 0.04 and 10.30 mM, respectively. Four samples of TTO tested showed anticholinesterase activity at IC50 values of 0.05, 0.10, 0.08 and 0.11 µL/mL, respectively. [22]
A study was conducted to measure the acaricidal effect of essential oil of M. alternifolia at different doses (4, 6, 8 and 10 µl) and for different exposure times (30, 60, 90 and 120 min) on nymphs of Ixodes ricinus. A dose of 8 µl tea tree oil was lethal for >70% of ticks when inhaled and this effect was enhanced when it was increased to 10 µl (>80%). Not only that, the effect was correlated with the duration of ticks’ exposure to tea tree oil, reaching a significant effect after 90 min exposure. [23]
Antimicrobial activity
Antiviral
The in vitro antiviral activity of M. alternifolia essential oil and its main components including terpinen-4-ol, alpha-terpinene, gamma-terpinene, p-cymene, terpinolene and alpha-terpineol was analysed against polio type 1, adeno type 2, ECHO 9, Coxsackie B1, herpes simplex (HSV) type 1 and 2 viruses by 50% plaque reduction assay. The anti-influenza virus assay was dependent on the inhibition of the virus-induced cytopathogenicity. Results showed that M. alternifolia and some of its components (the terpinen-4-ol, the terpinolene, the alpha-terpineol) inhibit influenza A/PR/8 virus subtype H1N1 replication but only a slight virucidal effect was observed against HSV-1 and HSV-2. [24]
Antifungal
The in vitro antifungal activity of the essential oil of M. alternifolia, has been evaluated against various dermatophyte species, yeast Candida and Malassezia furfur strains. Tea tree oil inhibited the growth of dermatophytes (MIC: 1,112.5 – 4,450.0 μg/mL), Candida and Trichosporon (MIC: 2,225.0 – 4,450.0 μg/mL) and the most susceptible is the lipophilic yeast M. furfur (MIC: between 556.2 and 4,450.0 μg/mL). [25]
Tea-tree oil may be useful in the treatment of yeast and fungal mucosal and skin infections due to its inhibitory activity in vitro against Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Aspergillus niger, Penicillium species, Microsporum gypsum and Candida albicans. [26] [27]
Antibacterial
The susceptibility of a range of transient and commensal skin flora to the essential oil of M. alternifolia was determined by using a modified broth microdilution method. The results showed that Serratia marcescens had the lowest MIC90 of 0.25% whereas the highest was 3% for Pseudomonas aeruginosa. Besides that, the lowest minimum bactericidal concentration (MBC90) was 0.25% for S. marcescens and Klebsiella pneumoniae, whereas the highest was 8% for Staphylococcus capitis. S. aureus and most of the gram-negative bacteria tested were more susceptible to tea tree oil than the coagulase-negative staphylococci and micrococci. [28] The MIC90 of tea tree oil for E. coli was 0.25% while for S. aureus it was 0.50%. [29]
A study analysed 64 methicillin-resistant Staphylococcus aureus (MRSA) isolates from Australia and the United Kingdom, including 33 mupirocin-resistant isolates. The MICs and MBCs for the Australian isolates were 0.25% and 0.5%, respectively, while those for the UK isolates were 0.312% and 0.625%, respectively. [30]
There are also other studies done on the susceptibility of MRSA to tea tree oil which showed no huge differences compared to antibiotic-sensitive organisms. [31][32][33]
Toxicity
No documentation.
Clinical Data
Clinical findings
Urinary Tract Infections
A randomized, double-blind, placebo-controlled trial evaluated the efficacy of the essential oil in the treatment of 26 women with chronic idiopathic colibacilli cystitis. Patients were treated with 8 mg essential oil, in an enteric capsule form, orally three times daily for 6 months. The results showed that 54% of the essential oil-treated groups were free of symptoms compared with only 15% in the placebo group. However, approximately 50% of the asymptomatic patients still showed evidence of colibacilli and leukocytes in their urine. [34]
Vaginal Infections
Based on a study 40% emulsified solution of tea tree oil in 13% isoprophyl alcohol is effective in the treatment of 130 women with cervicitis or vaginitis due to Trichomonas vaginalisor vaginitis due to Candida albicans. Intravaginal application of tampons saturated with a 20% emulsified solution healed cervicitis caused by Trichomonas vaginalis after four weekly treatments. In patients with vaginitis due to Trichomonas vaginalis, intravaginal application of a 1% emulsified solution using a saturated tampon, as well as vaginal douching, resulted in clinical cures and restoration of the cervix. [35]
According to another study without controls, 28 women with vaginitis due to C. albicans were treated with vaginal pessaries (containing 0.2 g essential oil) every night for 90 days. After 30 days of treatment, 24 patients were already free of symptoms such as leukorrhea and burning sensation, and 21 were free of C. albicans. [34]
Acne
A randomized, single-blind, comparison trial analysedthe safety and efficacy of topical application of a gel containing either 5% essential oil or 5% benzoyl peroxide in the treatment of mild to moderate acne in 119 patients. The results showed that both gelssignificantly reduced the number of inflamed and non-inflamed lesions after 3 months of daily treatment (p<0.001), although the onset of action of the oil-containing gel was slower than the benzoyl peroxide-containing gel. Patients treated with the oil-containing gel reported fewer side effects than those treated with the benzoyl peroxide-containing gel. So essential oil was more effective as compared to benzoyl peroxide. [36]
Tinea Pedis
A randomized double-blind, placebo-controlled clinical trial evaluated the efficacy of a cream containing either 10% (w/w) essential oil, 1% tolnaftate or a placebo in the treatment of 104 patients with tinea pedis due to Trichophyton rubrum, Trichophyton mentagrophytes and Epidermophyton floccosum. After application of the cream twice daily for 4 weeks, both the essential oil-treated group and tolnaftate-treated group demonstrated significant improvement in the clinical symptoms of scaling, inflammation, itching and burning sensation, compared with the placebo group (p < 0.001). [37]
Fungal nail infections
A randomized, double-blind, placebo-controlled study assessed the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% M. alternifolia oil incorporated in a cream to manage toenail onychomycosis of 60 patients. After 16 weeks, 80% of the patients using the medicated cream were cured. No relapse was seen during follow up in the cured patients. [38]
A randomized, double-blind, multicentre comparison trial evaluated the efficacy and tolerability of the topical application of 100% essential oil or 1% clotrimazole in the treatment of 117 patients with toenail onychomycosis. The patients received twice-daily topical applications of either one for 6 months, and debridement and clinical assessment were performed at 0, 1, 3 and 6 months. After 3 months, approximately 50% of each group reported improvements. After 6 months of treatment, clinical assessment documented partial or full resolution in approximately 60% of each group. [39]
Warts
The topical application of tea tree oil once daily for 12 days successfully eradicated warts and re-epithelization occurred. [40]
Lice eradication
An in vitro study showed that 97.6% of subjects were louse-free one day after the last treatment oftopical application of the pediculicide containing tea tree oil as compared with 25% of those using pyrethrin-based products in the treatment of Pediculosis capitis (head lice infestation). [41]
Anti-inflammatory activity
20 minutes after the 27 volunteers injected intradermally in each forearm with histamine diphosphate (5 µg in 50 µL), 25 µL of 100% tea tree oil was applied topically to the study forearm of 21 volunteers, whereby the rest was applied with 25 µL of paraffin oil. Results showed significant reduction of histamine-induced skin inflammation based on the mean weal volume after tea tree oil application (10 minutes after tea tree oil application, p=0.0004, Mann-Whitney U-test). [42]
Oral infections
In an open study, 27 patients with acquired immunodeficiency syndrome (AIDS) and oral candidiasis clinically refractory to fluconazole were randomly assigned to receive either an alcohol-based or an alcohol-free melaleuca oral solution four times daily for 2 to 4 weeks. Results showed 60% of patients demonstrated a clinical response to the melaleuca oral solution at 4-week evaluation. [43]
In a study, 301 yeasts isolated from the mouths of 199 patients with advanced cancer were shown to be susceptible to tea tree oil, including 41 yeasts that were known to be resistant to both fluconazole and itraconazole. [44]
Precautions
Not for internal use. Keep out of reach of children. Avoid using it in cases of known allergy to plants of the Myrtaceae family. [47][48][49]
Side effects
No documentation.
Pregnancy/Breast Feeding
No documentation.
Age limitation
No documentation.
Adverse reaction
Dermatological Adverse Reaction
Allergic contact eczema has been reported. [45]
Erythema multiforme-like reaction secondary to allergic contact dermatitis from tea tree oil has been reported. [46]
Effects of Ingestion
Accidental ingestion of less than 10mL essential oil caused confusion, drowsiness, loss of coordination and even became unresponsive requiring endotracheal intubation. [47][48][49]
Interaction & Depletion
Interaction with drug
Antagonistic interaction was noted in vitro between tea tree oil and conventional antimicrobials (ciprofloxacin/amphotericin B) when used in combination. [50]
Interaction with other Herbs
No documentation.
Contraindications
M. alternifolia is contraindicated in cases of known allergy to plants of the Myrtaceae family.
Case Report
Dermatological Adverse Reaction
Allergic contact eczema has been reported. [45]
Erythema multiforme-like reaction secondary to allergic contact dermatitis from tea tree oil has been reported. [46]
Effects of Ingestion
Accidental ingestion of less than 10mL essential oil caused confusion, drowsiness, loss of coordination and even became unresponsive requiring endotracheal intubation. [47][48][49]
Poisonous Management
No documentation.
Line Drawing
No documentation.
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