Ruta (PROSEA)

Plant Resources of South-East Asia
Introduction

List of species

Ruta L.

Protologue: Sp. pl. 1: 383 (1753); Gen. pl. ed. 5: 180 (1754).

Family: Rutaceae

Chromosome number: x = unknown; R. angustifolia: 2n= 40

Major species

Ruta angustifolia Pers.,
R. chalepensis L.

Vernacular names

Rue (En)
Indonesia: godong minggu (Javanese), inggu (Sundanese), anruda busu (Makassar)
Malaysia: aruda, sadal
Vietnam: cửu lý hương, ân hương.

Origin and geographic distribution

Ruta comprises about 8 species and is found from Macaronesia eastward through the Mediterranean to South-West Asia. Ruta has also been introduced in other parts of Asia, the West Indies, South and Central America.

Uses

Ruta acts as a rubefacient and the oil may even blister the skin. This may well explain its traditional use in South-East Asia, in combination with turmeric, for itch. It is assumed that it kills the mites and stimulates the skin. Internally it has an anti-aphrodisiac effect and slows the pulse, possibly explaining its traditional use in mixtures that are applied to the wrist and temples to treat convulsions in hysteria and as a treatment for fevers. In Malaysia, leaf sap is used as eardrops for earache. In Java, the leaves are an ingredient of a mixture for coughs.

Ruta has traditionally been used as a condiment, excessive use is, however, dangerous. Its toxic effects are clearly dose-dependent. It is potentially toxic and carcinogenic when consumed orally, and can produce dermatitis when touched. Used internally, the leaves and oil can cause haemorrhages, miscarriage and abortion, and have been used as such since ancient times. It may further cause vomiting, gastroenteritis, swelling of the tongue, coldness of the extremities, and even death. Rue oil is used as an anthelmintic, antispasmodic, anti-epileptic, rubefacient and emmenagogue especially in veterinary medicine.

The oil is used as a flavouring agent and in perfumes and soap scents. Oils rich in methyl nonyl ketone are used for the preparation of methyl-n-nonyl acetylaldehyde, widely applied as a synthetic perfume.

Production and international trade

In South-East Asia, Ruta is only used on a local scale. Commercial production of rue oil is centred in the Mediterranean.

Properties

Ruta is characterized by the presence of alkaloids (acridonal-, chinolone-, furochinolone- type alkaloids, and quaternary furochinolines), (furano-)coumarins and essential oils. The compounds isolated from R. angustifolia, R. chalepensis and R. graveolens L. are essentially the same; quantitative differences are observed, however, between the species, but are of the same magnitude as those observed from different sources of the same species. Qualitative and quantitative differences are also found for the different parts of the plants.

In general, characteristic components of Ruta essential oils include 2-nonanone and 2-undecanone, of which the concentrations vary between species, parts and sources.

Major compounds isolated from the roots of R. chalepensis are the furochinolin alkaloids, kokusaginin, skimmianin and graveolin, the acridonal alkaloids 1-hydroxy-N-methylacridon and chaloridon, and the furanocoumarin, chalepensin. From the dried plant, major compounds isolated include the furochinolin alkaloids, kokusaginin, skimmianin, graveolin, γ-fagarin, and dictamnin, the acridonal alkaloid, arborinin, and the (furano-)coumarins, bergapten and chalepensin.

Bergapten (or 5-methoxypsoralen) and chalepensin belong to the family of the linear furanocoumarins, which are known to have phototoxic activity. Dermatosis may arise after plant material containing these compounds comes into direct contact with the skin, if this is immediately followed by exposure to UV-A light, e.g. from the sun. The mechanism of photosensitization by linear furanocoumarins is based on interference with DNA base pairs. Energy provided by UV-A irradiation leads to the formation of additional products between the furanocoumarin and cytosine and thymine bases. This bridge-building inhibits the replication and transcription of DNA and, consequently, the synthesis of RNA and proteins and the occurrence of cell division.

Furthermore, ethanol extracts of air-dried flowering material of R. chalepensis have been studied in various models. Oral administration at a dose of 500 mg/kg significantly reduced carrageenan induced oedema in rats. Similar results were reported using the cotton-pellet granuloma test model. Additionally, intraperitoneal administration at 100 mg/kg significantly reduced subcutaneously induced (yeast suspension) fever in mice. By using the same route, doses of 50, 100 and 500 mg/kg also significantly reduced motility in mice. No analgesic activity was observed in the hot-plate test with mice, however. Of the isolated compounds, chalepsin at an i.p. dose of 10 mg/kg significantly prolonged hexobarbital-induced sleeping time in mice.

Finally, a hexane extract of R. chalepensis shows strong molluscicidal activity against the schistosomiasis-transmitting snail Bulinus truncatus with an LC₉₀ value of 2.23 mg/l. Ethanolic extracts furthermore showed in vitro activity against the bacteria Staphylococcus aureus and Pseudomonas vulgaris (disk diffusion assay).

For R. graveolens some 40 alkaloids (examples include graveolin, γ-fagarin, skimmianin, arborinin, furacridon), more than 40 coumarins and furanocoumarins (linear types: e.g. bergapten, chalepensin, psoralen, xanthotoxin) and some 30 compounds in the essential oil (predominantly 2-nonanone and 2-undecanone) have been identified in various plant parts.

R. graveolens essential oil has a reported spasmolytic activity on the isolated rabbit ileum. Furthermore, the in vitro anthelmintic activity of the oil is proportional to the nonylmethylketone concentration. The LD₅₀ for Tubifex rivulorum was 0.1-0.15 g/100 ml, for Hirudo officinalis 0.075-0.125 g/100 ml and for Ascaris suilla 0.06-0.12 g/100 ml. An LD₁₀₀ for Anuillula aceti was achieved after 10 minutes at 0.2 g/100ml and after 45 minutes at 0.02 g/100 ml.

In addition, the methanol extract of the plant has a spasmolytic effect on the isolated rabbit ileum. The active principles have been identified as the coumarin derivates bergapten, psoralen and xanthotoxin, several furochinoline type alkaloids, and the acridon alkaloid arborinin. Furthermore, the spasmolytic activity of isolated rutamarin (a coumarin) and arborinin in various animal models was found comparable with that of papaverin. Other effects of arborinin also include inhibition of the histamine induced bronchospasms in guinea-pigs after application of a dose of 10 mg/kg intravenously, and anti-exudative activity in rats (3 mg/kg, s.c.) by using the dextran-oedema model.

Information on the antifertility effect of rue presents a mixed picture.

Whereas oral consumption of the essential oil induces abortion in guinea-pigs and humans, this probably has to be attributed to a general toxic effect. The essential oil has no effect on the isolated uterus in (non-)pregnant cats or the isolated oviduct in (non-)pregnant women. An ethanol extract of the plant, however, shows a significant anti-implantation effect, an increased absorption rate and an overall reduced pregnancy ratio in albino rats. Petroleum ether and methanol extracts are reported to have similar results, whereas benzene and chloroform extracts merely have a toxicological effect. None of the extracts had any effect on the golden hamster. The antifertility effect is attributed to the furanocoumarin, chalepensin, which has a very narrow therapeutical range. In view of the known variations in concentration in different source materials, this may very well explain the somewhat contradictory research findings for the various test systems.

Adulterations and substitutes

Alkaloids of the types present in Ruta species have also been found in several other genera belonging to the Rutaceae. Examples include kokusaginine and skimmianine, which are also reported for Glycosmis, Orixa and Zanthoxylum species.

Description

Perennial herbs, more or less woody at the base.
Leaves spirally arranged, 2-3-pinnatisect, obovate to oblong-obovate in outline, ultimate segments linear to obovate; petiolate or not; stipules absent.
Inflorescence cymose, terminal or in the upper leaf axils, often combined into a corymb, bracteate.
Flowers 4(-5)-merous, the lower ones bisexual, the upper ones male; petals cucculate, dentate or ciliate or more rarely entire, yellow; anthers twice as many as the petals; ovary superior, semi-globose, 4-5-lobed, 3-5-celled.
Fruit a capsule, dehiscent at the apex only.
Seed angulate.
Seedling with epigeal germination.

Growth and development

Flowering phenology patterns of protandrous R. angustifolia populations in Spain showed 87.5% overlap between male and female phases. Male flowers offered a higher nectar reward than female flowers, and higher visitation rate occurred during the population male phase. Flowers were visited by different unspecialized insects. Bagging experiments showed a clear trend to allogamy, but a limited production of fruits and seeds was observed when pollinators were not available. In Java, R. angustifolia does not flower at elevations below 1000 m altitude. At higher elevations it flowers from March-October.

Other botanical information

The botanical identity of Ruta growing in South-East Asia is unclear. The taxonomy of Ruta is already complex in Europe, the Mediterranean and the Near East. The name R. angustifolia as referring to small-leaved plants has been merged with R. chalepensis as well as R. graveolens, sometimes as a full synonym, sometimes retained at subspecies level. The chemical composition of the three species is almost identical and as Ruta is only known in South-East Asia in cultivation, the name R. angustifolia has been retained in this treatment.

Ecology

Ruta will thrive under fairly dry conditions in partial shade but will survive successfully in full sun. It is easily grown on any soil but prefers a well-drained calcareous clayey soil.

Propagation and planting

R. angustifolia and R. chalepensis are primarily propagated by seed. They can also be reproduced by layering, division of roots, and from cuttings. The latter means of propagation is advantageous at lower elevations in the tropics where it is reported to flower rarely.

In vitro production of active compounds

Research has concentrated on R. graveolens, and tissue cultures and cell suspension cultures have been established using explants of stems, roots or leaves harvested from whole plants or plantlets. Various media and phytohormones have been used. Cultures are characterized by easy organogenesis, an autothrophic aptitude to phytohormones and also towards light and especially strong biogenetic potentialities. A wide range of the pharmacological active compounds isolated from the plants are also produced by the tissue cultures and cell suspension cultures.

Husbandry

In South-East Asia Ruta is only known in cultivation and as a potplant. It may be pruned back to encourage fresh growth.

Harvesting

In South-East Asia leaves and flowering shoots of Ruta are collected whenever the need arises.

Handling after harvest

The aboveground non-woody parts of Ruta are preferably dried in the shade, and should be regularly turned as they do not dry easily.

Genetic resources and breeding

Within South-East Asia, there might be some danger of genetic erosion. Ruta has been introduced in the region and therefore the genetic basis might be limited. Furthermore, plants flower only occasionally and are mostly reproduced vegetatively.

Prospects

Application of the linear, phototoxic furanocoumarins in medicine as found in Ruta is well documented, for instance in the treatment of psoriasis. They therefore merit further research on their potential as a local- or industrial source. Other constituents (e.g. arborinin) might also have future potential.

Literature

Bonet, A., 1992. Reproductive biology of Ruta angustifolia Pers. in the Catalonian coastal range. Folia Botanica Miscellanea 8: 113-124.
Borges del Castillo, J., Rodriguez Luis, F. & Secundino Lucas, F., 1987. Phytochemical study of Ruta angustifolia Pers. Anales de Química Serie C Química Orgánica y Bioquímica 83(1): 15-17. (in Spanish)
Jansen, P.C.M., 1981. Spices, condiments and medicinal plants in Ethiopia, their taxonomy and agricultural significance. Pudoc, Wageningen, the Netherlands. pp. 104-111.
Hänsel, R., Keller, K., Rimpler, H. & Schneider, G. (Editors), 1994. Hagers Handbuch der Pharmazeutischen Praxis. Band 6: Drogen P-Z [Hagers handbook of the practice of pharmacology. Vol. 6: drugs P-Z]. 5th Edition. Springer Verlag, Berlin, Germany. pp. 506-521. (in German)
Hmamouchi, M., Lahlou, M. & Agoumi, A., 2000. Molluscicidal activity of some Moroccan medicinal plants. Fitoterapia 71(3): 308-314.
Petit-Paly, G., Rmawat, K.G., Chenieux, J.C. & Rideau, M., 1989. Ruta graveolens: In vitro production of alkaloids and medicinal compounds. In: Bajaj, Y.P.S. (Editor): Biotechnology in agriculture and forestry 4. Medicinal and aromatic plants II. Springer Verlag, Berlin, Germany. pp. 488-505.

Selection of species

Authors

Rina R.P. Irwanto