Zanthoxylum (PROSEA Medicinal plants)

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Plant Resources of South-East Asia Introduction

List of species

Zanthoxylum L.

Protologue: Sp. pl. 1: 270 (1753); Gen. pl. ed. 5: 130 (1754).

Family: Rutaceae

Chromosome number: x= 16, 17, 18; Z. armatum: 2n= 66, Z. nitidum, Z. rhetsa: 2n= 68

Major species

Zanthoxylum armatum DC., Z. nitidum (Roxb.) DC., Z. rhetsa (Roxb.) DC.

Vernacular names

• Ivy-rue, thorny yellow-wood (En)
• Malaysia: chenkring, hantu duri (Peninsular)
• Vietnam: sẻn.

Origin and geographic distribution

Zanthoxylum comprises about 200 species and has a pantropical distribution with a few representatives in temperate eastern Asia and North America. Most species occur in South America. The genus is found throughout South-East Asia and in northern Australia and the Pacific; there are 20 species within Malesia.

Uses

Throughout Asia numerous Zanthoxylum are widely used in folk medicine. The fruits are widely used, but also the leaves, bark and roots are employed, and the essential oil from the fruits is well known. Apparently plant parts as well as the various species are to some extent mutually exchangeable. The fruits are applied for a variety of gastro-intestinal complaints, and credited with many more virtues. The bitterness of the bark has contributed to its use as a tonic. The bark of Zanthoxylum (e.g. Z. integrifoliolum (Merr.) Merr. from Taiwan and the Philippines) is also widely used as a remedy for snakebites. The bark but also other plant parts of various Zanthoxylum are used to stupefy fish. The roots are considered sudorific and antipyretic, and are used for gastro-intestinal affections and as an emmenagogue.

The dried fruits or the fruits with the seed removed of several Zanthoxylum are used as a condiment. In India, also young leaves of Z. rhetsa are eaten as a spice and condiment. The wood of Zanthoxylum is used for house building, furniture and various small articles such as jewelry boxes, tool handles, walking-sticks, carving and novelties.

Production and international trade

In South-East Asia Zanthoxylum is only used and traded at a local level. In more temperate continental Asia, however, the dried fruits of Zanthoxylum are widely used and traded.

Properties

Zanthoxylum species are known for their essential oils, which have a complex terpenoid composition. For instance, in the seed essential oil of Z. armatum (collected from India), linalol (87.7%) was the main constituent identified. The essential oil from aerial parts of Z. armatum collected in north-west India contained 33% monoterpene hydrocarbons. The predominant constituents included 1,8-cineole (= eucalyptol) (15.7%), linalol (18.8%) and undecan-2-one (17.0%).

The essential oil of the seeds of Z. rhetsa was analyzed by GC-MS. The monoterpenes sabinene, limonene,α- andβ-pinene, p-cymene, as well as the monoterpene alcohols terpinen 4-ol andα-terpineol, were the dominant constituents that were responsible for the characteristic odour of seeds.

The seed essential oil showed anti-inflammatory activity against the exudative phase of inflammation in formalin- and carragenin-induced rat’s hind-paw oedema models. Local anti-inflammatory activity was furthermore confirmed in clinical trials by topical application in cases of inflammatory dermatosis. The oil also showed local anaestethic activity by infiltration and corneal application in guinea-pigs, its maximum potency at a concentration of 0.2%; however, it lacked surface anaesthetic activity. In addition it produced a transient fall in blood pressure in cats an dogs.

The essential oil from the fruits of Z. rhetsa showed stronger in vitro anthelmintic activity than piperazine against Taenia solium , Ascaridia galli and Pheretima postuma .

In tests with 15 compounds isolated from the essential oil of Z. avicennae, using 8 moulds (Aspergillus niger, A. sydowi, A. terreus, Penicillium chrysogenum, Paecilomyces varioti, Chaetomium globosum, Cladosporium herbarum and Trichoderma sp.), citral, 1-octanol, 4-methyl-6-acetoxyhexanal and linolool showed strong antimildew activities.

The essential oil obtained by steam distillation of the seeds of Z. armatum exhibited strong antibacterial activity against Escherichia coli, Vibrio cholerae, Micrococcus pyogenes var. aureus, Shigella dysenteriae and Salmonella typhi. Furthermore, the essential oil of the fruits of Z. armatum proved to be insect repellent to Aulacophora foveicollis and fungistatic against aflatoxin-producing strains of Aspergillus flavus and A. parasiticus at a minimum dose of 2 ml/l. The fungistatic properties of the oil were not affected by high temperature, prolonged storage or increased inoculum. Additionally, in field trials on persistence of leech repellent properties, the essential oil of Z. armatum was compared with the following chemicals: N,N-diethyl phenyl acetamide (DEPA), N,N-diethyl-m-toluamide (DEET), 3-acetyl-2-(2,6-dimethyl-5-heptenyl)oxazolidine (Citronyl), dimethyl phthalate (DMP) and N-benzoyl piperidine (NBP). DEPA and DEET were found to be the best. However, Z. armatum oil was comparable with Citronyl and exhibited far better results than DMP and NBP.

The accumulation of alkaloids is also characteristic for several members of this genus. Z. nitidum DC. is a source of nitidine, a benzo[ c ]phenanthrine alkaloid reported to have antitumour activity. Other alkaloids isolated include chelerythrine, oxynitidine, oxychelerythrine, skimianine, magnoflorine, (+)-tembetarine and (+)-isotembetarine. A methanol extract of Z. nitidum was furthermore found to inhibit topoisomerase I-mediated DNA relaxation and stabilize the covalent binary complex between the enzyme and DNA. The extract was subjected to bioassay-guided fractionation; three strongly inhibitory principles were identified as the alkaloids nitidine, chelerythrine and isofagaridine.

Avicine pseudocyanine is a semisynthetic derivative of avicine, a benzo[ c ]phenanthrine alkaloid isolated form Z. integrifoliolum. The compound concentration-dependently inhibits platelet aggregation and release reaction induced by a variety of reagents: collagen, trimucytin (a collagen-like snake venom protein isolated from Trimeresurus mucrosquamatus). Additional phytochemical investigations of this species led to the isolation and identification of several other compounds. These include alkaloids such as (-)-tetraberberine, skimmianine, canthin-6-one, rutaecarpine, atanine, lignans (e.g. sesamin, pinoresinol-di-3,3-dimethylallyl ether, pinoresinol-3,3-dimethylallyl ether), flavonoids (tambulin, prudomestin) and several isobutylamides. Evaluation of the biological activity revealed that rutaecarpine, tetrahydroberberine, canthin-6-one, tambulin, prudomestin and the isobuthylamides lanyuamide-I and -II, tetrahydrobungeanool, 2E,4E,8Z,11Z- and 2E,4E,8Z,11E-2'-hydroxy-N-isobutyl-2,4,8,11-tetradecatetraenamide,γ-sanshoöl and hydroxy-γ-sanshoöl displayed strong antiplatelet aggregation activity in vitro.

Biological effects of crude extracts of Zanthoxylum include 2.5% and 5% petroleum ether extracts of Z. rhetsa and Z. armatum which possessed antifeedant properties against 5th-instar larvae of Diacrisia obliqua (Spilosoma obliqua) and adults of Sitophilus oryzae.

Finally, a methanol extract from Z. armatum bark from Nepal was investigated for its antiproliferative activity against the growth of human keratinocytes (HaCaT cells). The extract was highly active with an IC₅₀ value of 11Œºg/ml. The antiproliferative activity was not due to cytotoxic effects on cell membranes, as documented by the activity of lactate dehydrogenase released from the cytoplasm of keratinocytes, which did not exceed that of the control value. Furthermore, the extract also protected against radical-induced damage to model membranes stimulated with 2,2'-azo-bis(2-amidinopropane)-dihydrochloride.

Adulterations and substitutes

Alkaloids of the types present in Zanthoxylum have also been found in several other genera belonging to the Rutaceae. Examples include skimmianine, which is also reported for Glycosmis , Orixa and Ruta species. Also canthin-6-one is found in the wood of Ailanthus altissima (Miller) Swingle (Simaroubaceae).

Description

• Evergreen or deciduous, dioecious or rarely monoecious, scandent or erect shrubs or small to medium-sized trees up to 35 m tall; bole up to 60 cm in diameter, occasionally larger, without buttresses; bark surface often studded with spines or prickles, grey or brownish, inner bark fibrous, aromatic.
• Leaves alternate, paripinnate or imparipinnate; petiolate; stipules absent; leaflets opposite to alternate, 1-15 pairs, entire or glandular-dentate, with pellucid dots; stipellae absent.
• Inflorescence axillary or terminal, a panicle, raceme or cyme or rarely flowers solitary.
• Flowers unisexual or bisexual; perianth with 6-8 tepals or differentiated into 4-5 sepals and petals; stamens 4-6, rudimentary in female flowers; disk flat to cushion-like; ovary superior, 1-5-carpellate, rudimentary in male flowers, carpels free or fused at base, each with 2 ovules, styles fused to divergent, stigma capitate.
• Fruit composed of 1-5 free or basally fused follicles; exocarp glandular, red to black.
• Seed ovoid to globose, 1 per follicle, often hanging from a funiculus; testa black or reddish, glossy; endosperm present.
• Seedling with epigeal germination; cotyledons emergent; hypocotyl elongated.

Growth and development

Several Zanthoxylum are myrmecophytes, with hollow branches showing slit-like openings in which ants of the genera Camponotus and Crematogaster live. In Peninsular Malaysia Z. rhetsa is deciduous around March or April and flowers just after or just before the new leaves. In Java it flowers in December. The fragrant flowers are probably pollinated by insects. In Java ripe fruits of Z. rhetsa are available in February and March.

Other botanical information

Zanthoxylum belongs to the subfamily Rutioideae and includes the genus Fagara . It is often misspelled as Xanthoxylum . The variation as observed in Z. nitidum appears to correspond with ecological differences within its range. Large-leaved plants in general are found in rain forest and small-leaved ones in drier situations. Plants of the first group are high climbing lianas with leaves over 25(-40) cm long, leaflets chartaceous or subcoriaceous, dull above, pubescent below. This form predominates in Malesia. Plants of the second group are climbing or semi-erect shrubs with leaves less than (5-)25 cm long, leaflets coriaceous, shiny above, glabrous below. This form predominates in mainland Asia with some outliers at higher elevations in Malesia. However, intergradation is so complete, that no taxonomic rank is given.

Ecology

Zanthoxylum is found in primary and secondary forest and thickets, up to 2100 m altitude. It thrives in deep fertile soils that are moisture retentive but welldrained, with a position in full sun or semi-shade. Z. myriacanthum is locally common in secondary forest and thickets on hills and mountains. Z. rhetsa is generally found in rather dry, often monsoonal forest and thickets, up to 500 m altitude. It can be planted in the open provided it is above 400 m altitude. At lower altitudes it will benefit from some shade. It is not resistant to fire.

Propagation and planting

In general Zanthoxylum is propagated by seed. Assuming similarity between temperate and tropical species it may well be propagated by semi-ripe cuttings at the height of the growing season, root cuttings during the resting period or simply by removal of rooted suckers. Multiple shoots were induced from nodal explants of mature tree (MTN) origin and from cotyledonary nodes (CN) of Z. rhetsa . Both types of explants formed the maximum number of shoots on Murashige & Skoog's (MS) medium supplemented with 2% sucrose and 10 mg/l TDZ (thidiazuron). The shoots from MTN developed very slowly and could not be rooted in vitro. The shoots obtained from CN were 2-3 cm longer and were rooted ex vitro by pre-treatment with 1 mg/ml catechol for 0. 5 h. Plantlets were successfully established in soil.

Husbandry

At the beginning of the growing season Zanthoxylum may be pruned to remove dead or damaged wood.

Harvesting

Bark, leaves and roots of Zanthoxylum are collected whenever the need arises. Fruits are collected when ripe or just before when still green. In Vietnam roots of Z. nitidum are collected throughout the year and fruits are collected green.

Handling after harvest

In Vietnam both roots and fruits of Z. nitidum are dried in the sun or shade for storage and future use.

Genetic resources and breeding

Zanthoxylum species treated here are in general widespread and common throughout South-East Asia, and therefore are not endangered. The availability of Z. rhetsa in Bali (Indonesia) is seriously reduced due to exploitation for the handicraft industry.

There are no known breeding programmes of Zanthoxylum .

Prospects

Compounds with anti-platelet activity are of interest in medicinal reaserch. Therefore, alkaloids and other constituents of Zanthoxylum merit further research in order to evaluate their possibilites for future developments. Also its essential oils may become of interest as a local source of insect repellents.

Literature

• Chen, I.S., Chen, T.L., Chang, Y.L., Teng, C.M. & Lin, W.Y., 1999. Chemical constituents and biological activities of the fruit of Zanthoxylum integrifoliolum. Journal of Natural Products 62(6): 833-837.
• Council of Scientific and Industrial Research, 1976. The wealth of India: a dictionary of Indian raw materials & industrial products. Vol. 11. Publications and Information Directorate, New Delhi, India. pp. 17-25.
• Fang, S.D., Wang, L.K. & Hecht, S.M., 1993. Inhibitors of DNA topoisomerase I isolated from the roots of Zanthoxylum nitidum. Journal of Organic Chemistry 58(19): 5025-5027.
• Hartley, T.G., 1966. A revision of the Malesian species of Zanthoxylum (Rutaceae). Journal of the Arnold Arboretum 47: 171-221.
• Kumar, S. & Muller, K., 1999. Inhibition of keratinocyte growth by different Nepalese Zanthoxylum species. Phytotherapy Research 13(3): 214-217.
• Nath, D.R., Das, N.G. & Das, S.C., 1993. Persistence of leech repellents on cloth. Indian Journal of Medical Research 97: 128-131.

Authors

Tahan Uji