Articles

Melaleuca cajuputi Powell. (Myrtaceae)

Synonyms

Melaleuca leucadendra L.,Melaleuca leucadendron Linn., Melaleuca cajuputi subsp. cajuputi, Melaleuca cajuputi Powell subsp. cajuputi, Melaleuca trinervis Buch., Melaleuca saligna, Melaleuca leucadendron var. cajuputi (Powell), Melaleuca minor Sm., Melaleuca leucadendron var. minor (Sm.), Melaleuca mimosoides Schauer, Melaleuca leucadendron var. mimosoides (Schauer), Melaleuca amboinensis Gand., Melaleuca cajuputi subsp. cumingiana (Turcz.) Barlow, Melaleuca cajuputi subsp. platyphylla Barlow, Myrtus saligna, Myrtus leucadendra L, Leptospermum kucadendron (L.), Cajuputi leucadendron (L.) Rusby ex. 

Vernacular Names:

Malaysia Kayu Putih, Gelam
English Cajuput, Cajeput, Cajaput, Swamp tea tree, Paper Bark Tree (Australia), Punk Tree (USA), White Tea Tree, White Wood
China Bai Gian Ceng
India Kaayaaputi
Indonesia Kayu Putih, Gelam (Sunda, Java), Ghelam (Madura), Waru Gelang, Inggolom (Batak), Kayu Gelang, Bru Galang,  Waru Gelang (Sulawesi), Nggielak, Ngelak (Roti),lren, Sakelan (Piru), Irano (Amahai), Ai Kelane (Hila), Irono (Haruku), Ilano (Nusa Laut Saparuna), Elan (Buru).
Thailand Samet
Vietnam Chè Dong Tran, Chi Cay , Bach Thien Tang
France Cajuputier
Brazil Melalueca (Portuguese)
Portugal Cajupute

General Information

Description

Melaleuca cajuputi Powell is a member of the Myrtaceae family. The genus has been established since 1767 and can be found indigenously across the hot and humid climate zone of Australia to the Asian mainland. Specifically, it grows along the latitudinal range of 12°North to 18°South of the equator and can survive in a range of altitudes from measuring 5 m to 400 m. It is able to populate coastal, sub-coastal, riverbanks as well as the inlands. Based on its genetic distribution along the geographical lines, it was hypothesized that the species has spread naturally across Asia to Australia. In Asia, it has been cultivated for more than a hundred years. There are three known subspecies of M. cajuputi namely M. cajuputi subsp. cajuputi, M. cajuputi subsp. cumingiana (Turczaninow) Barlow and M. cajuputi subsp. platyphylla Barlow. [1-4][11][12][14]

This genus grows as shrubs or trees with single flexible trunk ranging from small tree to measure 25m in height. In some situations, it can grow up to 40 m. Its girth can grow to a diameter of measuring 1.2-1.5m. The branches are pendulous, grow in an irregular ascending manner with dense green foliage. The species can be characterized by the white or grayish papery bark that covers the trunk and branches. The bark is soft and spongy and flakes out in elongated papery pieces from time to time. The leaves are thin, narrow and lancet-shaped. It alternates on short foot-stalks and are shiny green or ash coloured. The leaves are highly aromatic and bitter to the taste. Oil from the leaves usually posses a greenish tint due to the traces of copper that have been found in it. The flower can be recognized by its creamy white elongated spiky petals. The fruit of this species grows to measure 2.5-3mm in length and 3-4mm wide and are usually light brown to dark brown in colour.  The seeds are very small and are obovoid in shape. [21][23]

The species is highly adaptable and can grow in a wide range of situations. It can survive on both waterlogged and well-drained soils. It is able to tolerate exposure to wind and is also resistant to fire. Its root system is quite extensive as it is able to develop adventitious roots when subject to prolonged flood and has the ability to grow from suckers.

Plant Part Used

Bark, leaves, twigs, fruit and wood.

Chemical Constituents

Over 40 compounds and volatiles had been found mainly from the leaves, fruits, twigs and seeds of this specie. Two different chemotypes had been determined which seemed to parallel its difference in terms of geographical location. The chemotype I consists of mono and sesquiterpenes while Chemotype II contains either methyleugenol as its principal component (95-97%) or E-methyl isoeugenol (74-88%) with lesser volume of methyleugenol (6-24%). [5]

Basically, 1, 8-cineole is the major constituent of the oil extracted from Chemotype I. In fact, the quality of the oil depends on the percentage of this particular constituent. It is found that poor growth conditions contributed to better oil quality with higher cineole content which suggested that a defense mechanism where high amounts of secondary substance were generated for survival purpose. [7] The percentage of 1, 8-cineole and the oil concentration in fresh leaves can be determined by near infrared spectroscopy. [18]

The volatile oil composition M. cajaputi leaves determined by gas chromatography-mass spectrometry (GC-MS) method revealed the oil to contain terpenoids 1,8-cineole (40–65%) as major component, with alpha-pinene, alpha-terpineol, nerolidol, limonene, benzaldehyde, valeraldehyde, dipentene and various sesquiterpenes as well as 3,5-dimethyl-4,6,di-o-methylphloroacetophenone. [8][14][15] Other components included l-pinene, terpineol, valeric, butyric, benzoic acids and aldehydes. [19] The sesquiterpene alcohols, azulene, dipentene, valeraldehyde and benzaldehyde were also found in the volatile oil of leaf and aerial parts. Betulin, friedelin, epitaraxeryl acetate were also found to be present.[11] The ursolic acid and betulinic acid were previously isolated from the flower and seed extracts.

The triterpenes were isolated from the heartwood, namely, eupha-7,24-diene-3,22-diol, 20-taraxastene-3,28-diol, 3,27-dihydroxy-28,20-taraxastanolide and 3-hydroxy-13(18)-oleanene-27,28-dioic acid. [16]

Not only the characteristic of the compounds vary between provenances, they also showed a significant variation among families-within-provenance group. [19] There seemed to be a varied composition of chemical constituents within the three known subspecies. Cajeputol, the aromatic ether was reportedly missing from the oil of M. cajuputi subsp. cajuputi which is the most commercially produced among the three subspecies. The oil yield ranged from 0.4% to 1.2% (w/w%, fresh weight).

The oil of M. cajuputi subsp. cumingiana, from Indonesia, Malaysia, Thailand and Vietnam showed a low constitution of 1,8-cineole (0-6%). It is made up of γ-terpinene (0–19%), terpinolene (0–22%) α -pinene (1–10%), α-thujene (0–8%), α-phellandrene (trace–2%), α-terpinene (0–3%), limonene (trace–3%) and p-cymeme (0–12%). Oxygenated monoterpenes were represented by terpinen-4-ol (0–6%) and α-terpineol (trace–3%) while the major sesquiterpenes detected in the oil were α-, and γ-eudesmol (0–2%), caryophyllene oxide (0–7%), α- and ß-selinene (0–4%), viridiflorene (0–3%), humulene (4–14%), aromadendrene (0–5%) and ß-caryophyllene (7–44%). There was a small amout of cajeputol present in this subspecie depending on its geographical location. The species of M. cajuputi found in Thailand and Vietnam contains up to 2% cajeputol while the specie from Kalimantan, Indonesia and Malaysia contains up to 18%. Oil yield ranged from 0.3% to 0.5% (w/w%, fresh weight).

There are two chemotypes for the oils of M. cajuputi subsp. platyphylla. The oil composition for this subspecie is characterized by significant quantities of α-pinene (34–73%), with lesser amounts of 1,8-cineole (0.2–3%), γ-terpinene (trace–2%), p-cymene (trace–1%), terpinolene (trace–1%), ß-caryophyllene (2–14%), aromadendrene (1–9%), humulene (1–7%), viridiflorene (trace–3%), caryophyllene oxide (trace–2%), globulol (trace–6%), viridiflorol (trace–2%), spathulenol (trace–3%) and the absence of cajeputol. Oil yield of this chemotype was 0.1–0.4% (w/w%, fresh weight). A second chemotype, contains the ß-triketone, platyphyllol (21–80%), and cajeputol (0.6–51%). The oil yield of this chemotype ranges from 0.2% to 0.6% (w/w%, fresh weight). [3]

Traditional Use:

M.cajaputi is used in traditional preparations to relieve a myriad of diseases. It is used as an ointment to relief rheumatism, stiff joints, sprains, neuralgia, migraine and as a mosquito repellent. [8][19] It is also used as an anticonvulsant, sedative, and relaxant and as an analgesic. Besides, it is used to heal fresh wounds, as an antiseptic and is used as topical applications for skin problems such as psoriasis and eczema and as well as an antihelmintic and parasiticidal agent to treat roundworms, scabies and pediculosis. [13][14][19-21][23][28] It is also known traditionally as an antidandruff agent. [11]

Among Australian aborigines, the leaves of this species are used in the treatment of all kinds of diseases. The aromatic vapour from crushed leaves is used as an expectorant to reduce nasal and bronchial congestion. [3] The vapour of these crushed leaves in boiling water is used to treat colds, influenzas and fever through inhalation. Alternatively, the infused water is sipped. [4] It is also used in pediatrics treatment as a broad-spectrum medicine through whole body smoking if the patients display severe symptoms although the illness is undiagnosed. Besides that, the species is also used in the preparation of a non-specific tonic. [17]

The oil is used traditionally in the Malay Archipelago for the treatment of internal disorders, stomach and intestinal problems and as well as an insecticide because of its antibacterial properties. [7] Just like in the aboriginal culture, it is a popular medicine for almost any ailment. It is applied externally for massage. In cases of abdominal complaints, a few drops are sometimes swallowed. [10]

Pre-Clinical Data

Pharmacology

Anti-inflammatory activity

Ursolic acid, which is a triterpenoid that can be found in M. cajuputi was shown to possess anti-inflammatory property by inhibiting histamine release from mast cells. [27]

Antimicrobial activity

The chemical constituents of M. cajupti; viz, 1,8-cineole, (-)-linalool, (-)-terpinen-4-ol, (±)-α-terpineol  and 3,5-dimethyl-4,6-di-O-methylphloroacetophenone (or cajeputol) have been identified to possess antimicrobial activity. The platyphyllol and similar compounds found in the species that was used in bactericide and fungicide preparations had been patented. [3]

The piceatannol-a'-O- (6"-galloyl)-Glc, a derivative from M. cajuputi had showed antibacterial activity against four Helicobacter pylori strains (NCTC11638, ATCC43504, A-13, A-19)  with Minimum Inhibitory Concentration (MIC) values of 25, 50, 12.5, 25 μg/mL respectively. However, for E.coli strain JC-2, the MIC was >100μg/mL. The antibacterial activity was determined using agar dilution method. The lack of antibacterial activity against E. coli suggested that the compound has a narrow antibacterial spectrum. This indicated that it might be able to suppress H.pylori without affecting the intestinal bacterial flora. [6]

The oil from M.cajaputi was antimicrobial and hypermic in vitro. [8] It was active against Bacillus cereus and Staphylococcus aureus, but was inactive against Escherichia coli and Pseudomonas aeruginosa. [15]

Besides its antibacterial properties, the volatile fraction of the leaves of M. cajuputi has also been reported to contain antifungal activity. [29]

The ethanol extract from the fruits of M. cajuputi proved to be cytotoxic to Vero cells with complete detachment of cells from the dish surface at a concentration of 100μg/mL. Further study on HSV-1 infected female BALB/c mice was conducted to test the therapeutic efficacy of the extract. At the dose of 5mg/mice, the extract significantly slowed down the progression of skin lesions and all mice remained alive throughout the experiment despite its high cytotoxicity. It was suggested that the antiviral property of this extract was selectively absorbed from the alimentary tract or was converted into another active compound by the intestinal flora. It may even be possible that it is not related to the in vitro toxic compound. The essential oil of M. cajuputi has previously been reported to have antiviral activity against tobacco mosaic virus. [31]

Antioxidant and hepatoprotective activity

Ursolic acid (UA; 3-hydroxy-urs-12-en-28-oic acid), a steroid-like triterpene compound found in M. cajuputi was reported to have strong hepatoprotective activity against ethanol. In vitro condition, UA displayed higher protective effect against heart as compared to the liver. In vivo studies involving induction of ethanol toxicity in Wistar rats, the co administration of UA managed to control oxidative stress by decreasing lipid peroxidation products and increasing the activities of antioxidant enzymes. [24]

Anticancer activity

Piccatannol (trans-3,4,3’,5’-tetrahydroxystilbene, also known as 3-hydroxyresveratrol or astringinine) is a naturally occurring polyphenol and has been identified as an active component of M. cajuputi. It is a natural analog of resveratrol, a known anticancer agent although it might exhibit a slightly different biological activity. [33] The studies have shown that this compound was able to inhibit the growth of colorectal cancer cell lines and arrests Caco-2 cells in the S phase of the cell. [25]

Larvacidal, pesticidal and insect repellent activity

The compound extracted from M. cajuputi showed 12.50% mortality in 50 ppm and 27% mortality in 125% ppm concentration when tested against the mosquito Aedes albopictus first stage larvae. [13] The lethality test on brine shrimp Artemia salina showed an LC50 of 22.25 µg/mL after 24 hours. [15]

The oil of M. cajuputi was found to be effective in providing repellency against A. aegyti, A. stephensi and C. quinquefasciatus where it provided a protection time of 8 h at the maximum and a 100% repellency against all three species. [30]

A compound leucadenone A that was found in M. cajuputi was found to have a similar structure to a compound that was responsible for the antifeedant nature of Luma chequen (Myrtaceae) an aromatic, evergreen shrub, native to Chile which is immune to insects and pests. [26] M. cajuputi was also analysed for its antitermite activity. [32]

Inhibition of drug metabolizing enzyme

An experiment conducted to test the inhibitory activity of M. cajuputi on drug metabolizing enzymes CYP3A4 and CYP2D6 through radiometric measurement has shown that while it inhibits CYP2D6 activity in a time dependant manner, it was not a mechanism-based inhibitor as it did not show any inhibition activity in the presence of NADPH [20]

Psychopharmacological activity

The methyl eugenol which is highly abundant in chemotype II of the specie is a central nervous system depressant with anaesthetic, hypothermic and myorelaxant and anticonvulsant properties. [35]

Toxicities

Acute toxicity

The cajuput oil derived from M. cajuputi Powell showed a LD50 of 2-5g/kg in mice. [34] In rats, the oral LD50 was 3870mg/kg. [9] The lethal dose was 150-350 gm for a 70kg adult and between 20-50 gm for a 10kg child. The active compound, 1, 8-cineole was considered a non-irritant and has negligible risk of skin sensitivity and dermal irritation. [34]

The methyleugenol was found in abundance in chemotype II of the specie. Its content in the oil derived from this variety was as high as 99%. In acute toxicity studies, the oral LD50 was 850-1560 mg/kg for rats and 540mg/kg for mice. [35]

Subchronic toxicity

The subchronic toxicity of methyleugenol was determined in female and male rats administered with the compound for 14 weeks. A dose of 300 and 1000mg/kg caused a significant weight lost, choleostasis, altered hepatic functions, reduced serum total protein and atrophic gastritis. A dose of 100mg/kg and above has been shown to cause hepatocellular damage and adrenal hypertrophy.  The similar results were observered in mice. It was concluded that the liver and glandular stomach were affected in subchronic administration of methyleugenol. [35]

Chronic toxicity

In a 2 year study, the intraperitoneal administration of methyleugenol showed it to be a genotoxic carcinogen. There were no available data on reproductive toxicity and teratogenicity. However, putative mutagenicity has previously been reported. [35]

Clinical Data

Clinical Trials

The clinical studies employing the Pharmacia CAP-RAST test system were conducted to evaluate aeroallergens in allergic rhinitis and asthma patients in the dessert. The measurements were based on allergen specific IgE and total IgE in the serum. Each of these studies suggested that the pollen of M. cajuputi is a potential allergen with occurrence of up to 50% sensitivity among the patients. The rate seems to differ across gender and age. [36-38] 

Adverse Effects in Human:

No documentation

Use in Certain Conditions

No documentation

Age Limitations

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

The cajuput oil from M. cajuputi Powell was classified as non-toxic and non-sensitizing, although skin irritation may occur at high concentrations.

Case Reports

No documentation

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  1)  Botanical Info

References

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