Ailanthus (PROSEA Medicinal plants)

Plant Resources of South-East Asia Introduction

List of species

Ailanthus Desf.

Protologue: Mém. Acad. Sci., Paris 1786: 265 (1788).

Family: Simaroubaceae

Chromosome number: x = unknown; A. altissima: 2n= 64, 80, A. integrifolia subsp.calycina: 2n= 62, 64

• Ailanthus altissima (Miller) Swingle.

Ailanthus consists of 5 species and its natural distribution is from Turkestan and India to China, through Malesia towards the Solomon Islands and north-western Australia. Two species occur naturally within Malesia. A third, A. altissima, is widely cultivated throughout the world, and was introduced to Europe in 1751.

Ailanthus has a history of use in traditional medicine, particularly for the treatment of dysentery. A. altissima is noted as an antibacterial, anthelmintic, amoebicide and insecticide. The Indian A. excelsa Roxb. is noted as a medicine for respiratory problems and A. triphysa is applied for the treatment of dyspepsia, bronchitis, ophthalmia and snakebite. A. altissima is widely planted as an ornamental and shadetree, in shelter belts and for erosion control in tropical, subtropical and temperate countries. Ailanthus timber is used for furniture, laminated wood, ceilings, wooden shoes, moulding, toys, shingles, matchsticks, matchboxes, core of plywood, weather boards, interior trim, brush stocks, pattern making, paper pulp, fuel and charcoal. The leaves of A. altissima are used as fodder for silkworms in China.

The phytochemical composition of the bark and root bark of A. altissima, known as Ailanthi Cortex, has been quite extensively investigated. A variety of compounds were isolated, belonging to different groups. Most pronounced are the quassinoids (in the case of Simaroubaceae, sometimes also known as simaroubolides), of which components of several sub-types are present: the ailanthone type (e.g. ailanthone, chaparrinone, shinjulactone A (= 2-dihydroailanthone)), the ailanthone-ester type (e.g. glaucarubinone), the amarolide type (e.g. amarolide, shinjulactone H), the amarolide-acetate type (e.g. 11-acetylamarolide, shinjulactone K), the amarolide-monoglucoside type (e.g. shinjuglycoside E), and a non classified group (e.g. shinjulactone C, shinjudilactone). Furthermore, 2 categories of indole alkaloids (biosynthetically derived from the amino acid tryptophan) have been identified: the β-carbolines (e.g. 1-acetyl-4-methoxy-β-carboline) and the canthin-6-ones (e.g. canthin-6-one). Other isolated compounds include: 2,6-dimethoxybenzoquinone (characteristic for Simaroubaceae), a series of substituted naphthofuran-diones, and several phenolic compounds (e.g. 3,4,5-trimethoxyphenol-1-(6-xylopyranosyl)glucopyranoside, ferulic acid, vanillic acid).

Several isolated compounds from A. altissima possess pharmacological activities. The quassinoids ailanthone, glaucarubinone and 13,18-dehydroglaucarubinone were found to be active in the lymphocytic leukaemia system of mice (P-388) and Eagle's carcinoma of the nasopharynx (9KB) in vitro. Ailanthone and glaucarubinone also show strong antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in mice. However, their strong cytotoxicity limits their potential as future antimalarials. Short-term in vitro assays for tumour promoters and antitumour promoters (Epstein-Barr virus activation test) were also carried out for 14 quassinoids isolated from A. altissima. Some quassinoids, including ailantinol B, ailantinol C, aflanthone, and shinjulactone A, showed moderate activity at a molar ratio of 1:100 (TPA/quassinoids), and the results led to the elucidation of structure-activity relationships. Other activities include: a strong anti-amoebic activity against Entamoeba histolytica (ailanthone), a low in vitro antituberculosis activity (ailanthone, shinjulactone K and shinjudilactone), and a potent anti-ulcer activity for ailanthone and itsα-epoxide. Finally, shinjulactone C demonstrated inhibition of HIV replication in H9 lymphocytic cells with an EC₅₀ of 10.6 μM in the absence of cytotoxicity.

Of the alkaloids isolated, the cytotoxicity of canthin-6-one, 1-methoxycanthin-6-one, 5-methoxycanthin-6-one, and canthin-6-one-3-N-oxide to guinea-pig ear keratinocytes have been compared; the IC₅₀ values range from 1.11 to 5.76μg/ml. The β-carboline- and canthin-6-one alkaloids also have strong inhibitory effects on cAMP phosphodiesterases in vitro: 1-(1-hydroxy-2-methoxy)ethyl-4-methoxy-β-carboline and 5-hydroxymethyl-canthin-6-one have inhibitory activity in the same order of magnitude as the commonly used standard papaverine. The water extract of dried bark of A. altissima showed CNS-stimulant activity when administered intraperitoneally to mice. Lipid peroxide stimulation is also reported. Other pharmcological effects include severe rashes that develop after direct contact with the plant and nephrotoxic effects in rats after intragastrical administration of an extract at at a dose of 100 mg/kg.

Chaparrinone and 6-α-tigloyloxychaparrinone were shown to be responsible for the antitumour and cytotoxic activities of the root bark of A. integrifolia subsp. calycina. In addition to 6-α-tigloyloxychaparrinone (an α-ketol) A. integrifolia also contains the related quassinoid 6-α-tigloyloxychaparrin (a glycol). While both the glycol and α-ketol were found to significantly inhibit growth of the murine P-388 lymphocytic leukaemia cell line, only the α-ketol inhibited growth of the corresponding in vivo system as well.

Alcoholic extracts of leaf and stem bark of the Indian A. excelsa, at a dose of 250 mg equivalent of plant material/kg body weight, exhibited remarkably high anti-implantation and early abortifacient activities. These results bear out its traditional use as an abortifacient in some parts of India.

Methanol extracts of A. altissima furthermore showed antifeedant activity towards the beetle Epilachna varivestis as well as insect growth regulating activity. Topical application of a non-polar extract of A. altissima at 3μg/larva gave a 70-100% killing of the flour beetle, Tribolium castaneum, a pest in stored grain.

Aqueous extracts of A. altissima bark and foliage were previously shown to be toxic to other plants. The phytotoxic compound from the root bark was identified as ailanthone. This compound was highly phytotoxic, with concentrations of 0.7 ml/l causing 50% inhibition of radicle elongation in a standardized bioassay with garden cress (Lepidium sativum L.) seeds. Ailanthone exhibited potent pre- and postemergence herbicidal activity in greenhouse trials. Postemergence activity was especially striking; even the lowest application rate (0.5 kg/ha) caused complete mortality of 5 of the 7 plant species tested within 5 days of treatment. In contrast, the highest application rate (8 kg/ha) did not cause any detectable injury to A. altissima seedlings, indicating the presence of a protective mechanism in the producer species to prevent autotoxicity. Ailanthone was rapidly detoxified in field soil as a result of microbial activity. Applications of ailanthone equivalent to 0.5 and 4.0 kg/ha completely lost their phytotoxicity within 5 days when incubated in the presence of non-sterile soil. When incubated with sterile soil under identical conditions, however, ailanthone remained highly phytotoxic throughout the 21-day duration of the investigation. The high level of postemergence herbicidal activity in conjunction with its rapid biodegradation in soil suggest ailanthone may have potential for development as a plant-product herbicide.

• Dioecious, evergreen or sometimes deciduous trees up to 60 m tall; bole cylindrical, up to 85(-175) cm in diameter, buttresses absent; bark surface smooth or with irregular fissures; branches thick, with large leaf scars.
• Leaves more or less tufted at the end of twigs, arranged spirally, paripinnate or imparipinnate; stipules absent or caducous; leaflets opposite or subopposite, stalked, generally with some glands below or at the base.
• Inflorescence an axillary panicle.
• Flowers unisexual, 5(-6)-merous, zygomorphic; calyx small, 5(-6)-lobed or closed in bud and later irregularly splitting to the base (often in two parts), rarely cupular; petals 5(-6), free, induplicate-valvate in bud, concave, oblong or narrowly oblong; stamens 10, in female flowers either subnormal but without pollen, or vestigial, or absent; carpels 2-5, free, flat, in male flowers vestigial or absent, ovule 1 per locule, styles 2-5, free or united.
• Fruit a linear or oblong-lanceolate samara.
• Seed flat, orbicular or obovate or somewhat triangular, without endosperm, with a thin testa.
• Seedling with epigeal germination.

Ailanthus trees are in general fast growing. In Java, the mean height of planted A. integrifolia was 1.8 m 2 years after planting and 4.0 m 3 years after planting. In India, 10- and 50-year-old trees of A. integrifolia were 5 m and 39 m tall. In Pennsylvania (United States) 1-year old seedlings and root sprouts of A. altissima were on average 0.4 m and 0.8 m tall, respectively; 2-year old trees were 1.2 m and 1.7 tall respectively. Pollination is probably done by insects. The fruits are dispersed by wind. Natural regeneration of planted trees of A. integrifolia has been observed after only four years, but annual seed production varies greatly and seems unpredictable. Early flowering and early profuse production of seed is recorded for A. triphysa, although there are reports from India that every other year is a good seed year. A. triphysa is strictly cross-pollinated and seed maturation takes about 45 days.

Ailanthus belongs to the subfamily Simarouboideae, which is by far the largest subfamily within the Simaroubaceae. Numerous ornamental cultivars of A. altissima are registered.

A. integrifolia and A. triphysa occur in humid rain forest and in monsoon forest, and in Bengal (India) even in dry mixed forest. They occur scattered, never gregariously, in valleys, along streams and in open locations below 1000 m altitude. Variation in mean annual rainfall ranges from 1600 mm to 4560 mm. They are most often found on well-drained deep soils like fertile sandy loams. A. altissima prefers a cooler climate and is indigenous at higher elevations in North Vietnam.

Ailanthus is usually propagated by seed. A. altissima can be propagated by seed, but is usually multiplied by root suckers. Seedlings are adversely affected by high root-zone temperatures of 30-36°C. A. integrifolia is propagated by seed; it has about 1800 wingless seeds per kg and germination of fresh seed is about 60% but varies greatly. No pretreatment is required. Germination starts 3-6 weeks after sowing. Seeds of A. triphysa remain viable for about three months and germination takes place within 1-3 weeks; up to 100% germination has been observed. Seeds are broadcast and seedlings need only occasional watering, as they are susceptible to rot and damping-off. Seedlings of A. triphysa develop better when provided with partial shade, although the species is light demanding. When 8-10(-30) cm tall they are planted in fertile, well-drained sites at spacings of 1-2 m × 1-2 m. Seedlings are susceptible to damage by transplanting; the root system is especially vulnerable.

In vitro culture of Ailanthus using hypocotyl, stem, leaf or anther explants is usually on Murashige and Skoog medium with various supplements. Canthin-6-one and 1-methoxycanthin-6-one can be isolated from callus- and cell-suspension cultures of A. altissima. The combined yield of the two alkaloids was 1.38% of dry weight from callus and 1.27% of dry weight from cell suspensions. Whereas this alkaloid production is 100-fold greater than in the plant, production of quassinoids is very poor.

No serious diseases and pests have been recorded for Ailanthus, although A. triphysa seedlings are liable to attack by a fungus and a defoliator.

Trees of A. altissima harvested for medicinal purposes are usually felled in spring or autumn in temperate zones. Bark is removed and dried in the sun.

A. integrifolia is stored in a germplasm bank in India. A. altissima can be found in botanical gardens throughout the world but is nowhere maintained specifically for its medicinal value.

The biological activities of the quassinoids and canthin-6-one alkaloids of Ailanthus confirm the uses in traditional medicine; some of these constituents are of potential use as templates for new drugs. The herbicidal activity of ailanthone also has potential for development as a plant-product herbicide.

• Boer, E., Sosef, M.S.M., Wong, W.C., Lemmens, R.H.M.J. & den Outer, R.W., 1995. Ailanthus Desf. In: Lemmens, R.H.M.J., Soerianegara, I. & Wong, W.C. (Editors): Plant Resources of South-East Asia No 5(2). Timber trees: Minor commercial timbers. Backhuys Publishers, Leiden, the Netherlands. pp. 54-59.
• Dhanasekaran, S., Suresh, B., Sethuraman, M., Rajan, S. & Dubey, R., 1993. Antifertility activity of Ailanthus excelsa Linn. in female albino rats. Indian Journal of Experimental Biology 31(4): 384‚Äì385.
• Heisey, R.M., 1996. Identifications of an allelopathic compound from Ailanthus altissima (Simaroubaceae) and characterization of its herbicidal activity. American Journal of Botany 83(2): 192-200.
• Kubota, K., Fukamiya, N., Tokuda, H., Nishino, H., Tagahara, K., Lee, K.H. & Okano, M., 1997. Quassinoids as inhibitors of Epstein-Barr virus early antigen activation. Cancer Letters 113(1-2): 165-168.
• Okano, M., Fukamiya, N., Tagahara, K., Cosentino, M., Lee, T.Y., Morris-Natschke, S. & Lee, K.H., 1996. Anti-HIV activity of quassinoids. Bioorganic & Medicinal Chemistry Letters 6(6): 701-706.
• Roberts, M.F., 1991. Ailanthus altissima (the tree of heaven): in vitro culture and the formation of alkaloids and quassinoids. In: Bajaj, Y.P.S. (Editor): Biotechnology in agriculture and forestry. Vol. 15. Medicinal and aromatic plants III. Springer-Verlag, Berlin, Germany. pp. 39-57.

• Ailanthus altissima
• Ailanthus integrifolia
• Ailanthus triphysa

• J.L.C.H. van Valkenburg