Melaleuca cajuputi Powell

Last updated: 5 December 2016

Scientific Name

Melaleuca cajuputi Powell

Synonyms

Melaleuca commutata Miq. Melaleuca eriorhachis Gand.           Melaleuca lancifolia Turcz. Melaleuca minor Sm. Metrosideros comosa Roxb. Myrtus saligna J.F.Gmel. Nania comosa (Roxb.) Kuntze, Pimentus saligna (J.F.Gmel.) Raf, Melaleuca angustifolia (Blume) Blume [Illegitimate], Melaleuca saligna (J.F.Gmel.) Reinw. ex Blume [Illegitimate], Melaleuca trinervis Buch.-Ham. [Illegitimate]. [1]

Vernacular Name

Malaysia Kayu putih, gelam [2]
English Cajeput (also spelt 'cajaput' or 'cajuput'), swamp tea-tree [2]; white wood [3]
China Bai Gian Ceng [2]
India Kaayaaputi [2]
Indonesia Kayu putih (General); galam (Sundanese); gelam (Javanese, Madurese) [2]
Thailand Samet-khao [2]
Cambodia Smach chanlos [2]
Vietnam C[aa]y tr[af]m [2]
France Cajuputier [2]
United States of America Punk tree [2].

Geographical Distributions

Melaleuca cajuputi has been cultivated in Asia for several centuries. The approximate boundaries cover a latitudinal range from 18°S to 12°N from tropical, northern Australia (Queensland, Northern Territory, Western Australia) through south-western Papua New Guinea, Indonesia, Malaysia, Thailand and Vietnam. Natural populations of M. cajuputi in eastern Indonesia occur on the Moluccan Islands of Buru, Seram and Ambon. M. cajuputi has been planted since 1926 in central Java for oil production, using seed from Buru. It is also planted in Malaysia. [2]

Botanical Description

M. cajuputi is a member of the Myrtaceae family. M. cajuputi is an evergreen shrub or usually single-stemmed tree that can reach up to 25(-40) m tall with an extensive root system, sometimes with aerial adventitious roots. The bark is layered, fibrous, papery and grey to white. The crown is fairly dense, wide and somewhat silvery in appearance. The branches are smaller, with slender twigs but not drooping, and the young shoots are densely silky hairy with spreading fine hairs up to 2 mm long. [2]

The leaves are arranged alternate, flat and silky hairy to nearly hairless. The petiole is compressed to concave-convex, measuring 3-7(-11) mm x 1.1-2.3 mm and straight or curved. The leaves are elliptical to lance-shaped-elliptical but sometimes obliquely, measuring 5-10(-12) cm x 1-2.5(-6) cm, which is 2-10 times longer than wide, attenuated or sometimes abruptly rounded at the base. The apex is acute or narrowly obtuse, often apiculate, thinly coriaceous, dull green, finely but obscurely dotted with oil glands, with 5-7 prominent veins and prominent reticulation. [2]

The inflorescence is a terminal or upper-axillary spike, single or 2-3 together. The spike measures 3.5-9 cm x 2-2.5 cm. The rachis is 1-1.3 mm thick, enlarging at anthesis and densely pilose. The bracts are ovate, striate, villous and caduceus while the bracteoles are absent. The flowers are in triads, white, greenish-white or creamy. The sepal is 2.5-3 mm long, tubular and hairy while the tube is subcylindrical, measuring 1.2-1.9 mm x 1.5-2 mm and it is adnate to ovary (persistent in fruit) at the base, with 4 triangular to semicircular lobes that measure 0.7-0.9 mm x 1.2-2 mm with thin margin. There are 5 petals, measuring 2-2.7 mm x 1.8-2.3 mm, which are broadly obovate-spatulate with a short claw. The blade is suborbicular with 7 slender branched veins and streaked with glands. The numerous stamens are 7-10 mm long, white, hairless and arranged in bundles with a claw 1-3.5 mm long. There are 7-10 filaments per bundle that are attached to the upper margin of the claw. The free part is up to 8 mm long. Anthers are 0.4-0.55 mm long. The pistil is with a 3-celled ovary, which is about 1 mm long while the style is 6-9 mm long with a small stigma. [2]

The fruit is a cup-shaped to spherical, many-seeded capsule, and measuring 3-3.5 mm x 3.5-4 mm while the orifice is 1.5-2 mm in diameter with thin valves. The seed is linear and minute. [2]

Cultivation

M. cajuputi is primarily found in coastal areas of the hot humid tropics. In its natural habitat, the mean maximum temperature of the hottest month is usually 31-33°C and the mean minimum of the coolest month is 17-22°C. The area has up to 230 days of over 32°C mean temperature, but with few days exceeding 38°C. The area is frost-free. The mean annual rainfall is 1300-1750 mm with a strong monsoon pattern. [2]

M. cajuputi grows in a wide range of conditions, but most stands are found on low swampy coastal plains, sometimes immediately behind mangroves that may be flooded to a depth of over one metre during the wet season. The soils are often highly organic alluvial clays with poor drainage and very low fertility, and may be potentially acid sulphate (e.g. the Mekong Delta, Vietnam). It is resistant to fire, tolerates exposure to salt-laden winds, but not to saline waterlogged conditions. [2]

In swamps, M. cajuputi forms pure forests, mixed open forests or woodlands associated with M. leucadendra (L.) L., Barringtonia acutangula (L.) Gaertn., Lophostemon suaveolens (Sol. ex Gaertn.) Peter G. Wilson & J.T. Waterh. and Nauclea orientalis (L.) L. On less swampy sites, it grows with a wide range of eucalypts, acacias and other melaleucas including M. dealbata S. T. Blake, M. saligna Schau. and M. viridiflora Sol. ex Gaertn. Its altitudinal range in Australia is 5-150(-250) m. By contrast, populations in the Moluccas consist of extensive and mostly pure stands that extend inland on infertile, gravelly ridges with a subsoil of red-brown clay. These sites are often colonised by Imperata grassland. Most ridges and slopes of the northern coastline of Buru and those along the Wai Apu River (which drains to the east coast) have sparse vegetation comprising open woodlands and low shrub lands of M. cajuputi at 30-400 m altitude, covering some 100,000 ha. [2]

In western Seram, M. cajuputi occurs as an almost pure, continuous stand of some 150,000 ha along the Hoamoal Peninsula. Scattered populations occur on lowland plains and low undulating ridges at 30-150 m above sea level in Seram and also on smaller islands between Seram and Buru. Only a few scattered stands of M. cajuputi have been recorded in Ambon. In Vietnam, M. cajuputi forests once occupied most of the seasonally inundated acid sulphate soils (1.5 million ha) of the Mekong Delta, principally on Ca Mau Peninsula, in the Long Xuyen Quadrangle and on the Plain of Reeds. It is estimated that today only 120,000 ha of natural Melaleuca forest remains in the Delta.[2]

Chemical Constituent

M. cajuputi has been reported to containover 40 compounds and volatiles 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%).[4]

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. [5] The percentage of 1, 8-cineole and the oil concentration in fresh leaves can be determined by near infrared spectroscopy. [6]

M. cajaputi leaves has been reported to contain terpenoids 1,8-cineole (40–65%) as major component, with α-pinene, α-terpineol, nerolidol, limonene, benzaldehyde, valeraldehyde, dipentene and various sesquiterpenes as well as 3,5-dimethyl-4,6,di-o-methylphloroacetophenone. [7][8][9][7][8][9] Other components included l-pinene, terpineol, valeric, butyric, benzoic acids and aldehydes. [10] M. cajaputi leaf and aerial parts has been reported to contain volatile oil sesquiterpene alcohols, azulene, dipentene, valeraldehyde, benzaldehyde, betulin, friedelin and epitaraxeryl acetate. [11]  

M. cajaputi flower and seed extracts has been reported to contain ursolic acid and betulinic. M. cajaputi heartwood has been reported to contain triterpenes, 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. [12]

M. cajaputi has been reported to show a significant variation among families-within-provenance group. [10] 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 has been reported to contain 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). [13]

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). [13]

Plant Part Used

Bark, leaves, twigs, fruit and wood. [2]

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. [7][10] 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. [10][14][15][16][17] 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. [13] 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. [18] 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. [19]

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. [5] 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. [20]

Preclinical 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. [21]

Antimicrobial activity

The chemical constituents of M. cajuputi; 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. [13]

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 >100 μg/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. [22]

The oil from M. cajaputi was antimicrobial and hypermic in vitro. [7] It was active against Bacillus cereus and Staphylococcus aureus, but was inactive against Escherichia coli and Pseudomonas aeruginosa. [9]

Besides its antibacterial properties, the volatile fraction of the leaves of M. cajuputi has also been reported to contain antifungal activity. [23]

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 100 μg/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 5 mg/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. [24]

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. [25]

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. [26] 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. [27]

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. [14] The lethality test on brine shrimp Artemia salina showed an LC50 of 22.25 µg/mL after 24 hours. [9]

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. [28]

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. [29] M. cajuputi was also analysed for its antitermite activity. [30]

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. [15]

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. [31]

Toxicity

Acute toxicity

The cajuput oil derived from M. cajuputi showed a LD50 of 2-5 g/kg in mice. [32] In rats, the oral LD50 was 3870 mg/kg. The lethal dose was 150-350 g for a 70 kg adult and between 20-50 g 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. [32]

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 540 mg/kg for mice. [31]

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 1000 mg/kg caused a significant weight lost, choleostasis, altered hepatic functions, reduced serum total protein and atrophic gastritis. A dose of 100 mg/kg and above has been shown to cause hepatocellular damage and adrenal hypertrophy. The similar results were observed in mice. It was concluded that the liver and glandular stomach were affected in subchronic administration of methyleugenol. [31]

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. [31]

Clinical Data

Clinical findings

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. [33][34]

Adverse reaction

No documentation

Interaction & Depletion

No documentation

Contraindications

No documentation

Dosage

No documentation

Line drawing

191

Figure 1: The line drawing of M. cajuputi. [2]

References

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