Datura (PROSEA)

Plant Resources of South-East Asia
Introduction

List of species

Datura L.

Protologue: Sp. pl. 1: 179 (1753); Gen. pl. ed. 5: 83 (1754).

Family: Solanaceae

Chromosome number: x= 12; D. metel: 2n= 24, 48, D. stramonium: 2n= 24

Major species

Datura metel L.

Vernacular names

Thorn apple (En).
Pomme épineuse, stramoine (Fr)
Indonesia: kecubung
Malaysia: kechubong
Philippines: talong-punay (Tagalog)
Thailand: ma khuea ba (northern), lamphong (central)
Vietnam: càdộc dươc.

Origin and geographic distribution

Datura consists of approximately 10 species. It is believed to have originated in the southern part of North America (Mexico) but has since been introduced throughout the world. Some species have a long history in the Old World; the first references to them are from the middle of the 16th Century, and it is probable that they were introduced soon after the discovery of America. Only D. metel and D. stramonium are found in South-East Asia.

Uses

One of the main uses of D. metel in South-East Asia is for relieving asthma by smoking the dried leaves (and stems) or flowers. These "asthma cigarettes" have been shown to be very efficient in some cases, but in other cases they had little or no effect. However, indiscriminate use can have serious, or even fatal consequences. Other traditional uses include the treatment of haemorrhoids, boils and sores, skin diseases, rheumatism, headache, toothache, cholera, parasites such as ringworm, and as an anaesthetic. In India, D. metel has similar medicinal applications, and it is used additionally to treat hydrophobia, syphilis, inflammations of the breasts, epilepsy, convulsion, smallpox, mumps and leprosy. The Chinese use the flowers as anaesthetic and to treat asthma, cough, eruptions and swellings, and as a pain reliever. In Africa, D. metel is used as an abortifacient and to treat asthma.

In South-East Asia, D. stramonium, which is only found in Java, where it occurs locally, is sometimes used in traditional medicine to treat fatigue, pain and for curing sprains. Elsewhere, e.g. in India, Europe and Africa, it is used similarly to D. metel.

Datura species contain (-)-hyoscyamine and (-)-scopolamine as the major alkaloids. The natural occurring, pharmacologically active (-)-hyoscyamine is easily racemized, yielding (±)-hyoscyamine, commonly known as atropine. Its pharmacological effect is the same as that of (-)-hyoscyamine, but it must be used in double doses, because the (+)-isomer is practically inactive. (-)-Hyoscyamine and atropine have an anti-cholinergic (parasympatholytic) action. Modern therapeutic uses of these alkaloids therefore include: as a remedy against spasms in skeletal muscles, the urinary tract (e.g. in the treatment of renal colic), and the respiratory tract (asthma, bronchitis), for the suppression of secretions (e.g. overproduction of hydrochloric acid in the stomach, and as pre-anaesthetic to reduce salivation and respiratory secretions), as an antidote (treatment of cholinesterase-inhibitor poisoning, e.g. by nerve gases or certain insecticides), and in some special cases of Parkinsonism, acute myocardial infarction and bradycardia. (-)-Hyoscyamine and atropine are also available in eye drops for the treatment of uveitis and as a diagnostic aid (mydriatic) in certain eye examinations.

Like (-)-hyoscyamine, (-)-scopolamine has an anti-cholinergic effect, but unlike (-)-hyoscyamine, it is also a central nervous system depressant. Its uses include treatment of certain painful spasms, as a component of pre-anaesthetic medication and in ophthalmology, but the current main use is for the prevention of motion sickness (often applied as a skin patch behind the ear). The derivative scopolamine-butylbromide is frequently used in the treatment of gastro-intestinal spasms and renal or biliary colic.

The usefulness of Datura preparations in the treatment of asthma, and the route of application (cigarettes) is questionable and obsolete. A derivative, ipratropium bromide (isopropyl-atropine), is now commonly used instead. As an inhalation, it appears to be very effective in the treatment of chronic bronchitis, but somewhat less effective in asthma.

Hallucinogenic uses of Datura spp. are common among native tribes in Central and South America, but are apparently uncommon in South-East Asia. Although comparatively few cases of death have been recorded, its experimental use by, for example, adolescents, is very dangerous because the user often tries to harm himself or others. Criminals have used Datura to stupefy their victims. In Thailand, the seeds with a high concentration of scopolamine are used for this purpose.

Datura is also used in veterinary medicine, e.g. to control ectoparasites. D. metel has been shown to be efficient as a pesticide. Extracts have been used successfully against the larvae of the lepidopterous Plecoptera reflexa, which is a serious pest in Dalbergia sissoo Roxb. ex DC. plantations in India, and against cotton pathogens. They also reduce insect damage in stored wheat and maize, and are useful to control the root-knot nematode Meloidogyne javanica. D. metel is commonly cultivated as an ornamental, particularly the forms with double and purplish flowers.

Production and international trade

No trade statistics are available for Datura, although it is occasionally used for industrial extraction of tropane alkaloids. At the beginning of the 1980s the market prices of scopolamine hydrobromide and hyoscyamine sulphate were approximately US$ 850/kg and US$ 470/kg, respectively. In South-East Asia, Datura is only traded on a small scale on local markets.

Properties

The drugs used consist of the dried leaves, sometimes mixed with flowering tops and sometimes with fruits of Datura spp. The leaves are often rolled, wrinkled, agglomerated or broken in commercial samples. They have a characteristic, disagreeable odour and a slightly nauseous, bitter taste. The drug is rich in minerals (15-18%), and it must be emphasized that it is very toxic. The drug is generally used for the preparation of galenicals and not for the industrial extraction of alkaloids. The D. stramonium powder listed in the Dutch Pharmacopoeia (8^th edition) is titrated to contain 0.23-0.27% total alkaloids. It is an ingredient of antitussive syrups, but is mostly used in the form of cigarettes to relieve respiratory difficulties, together with other drugs.

The concentration of total alkaloids in the leaves of D. stramonium is normally 0.2-0.5%, with (-)-hyoscyamine and (-)-scopolamine (= (-)-hyoscine) as the major compounds and apoatropine, tropine, belladonnine and (-)-hyoscyamine-N-oxide as minor compounds. Biosynthetically these so-called tropane alkaloids are derived from the amino acid ornithine. An alkaloid content of about 0.6% has been reported for the flowers and fruits. The leaves of D. metel contain about 0.2-0.6% total alkaloids, the flowers 0.1-0.8% and the seeds 0.2-0.5%. (-)-Scopolamine is by far the chief constituent (up to 75% of the total alkaloid amount in mature leaves), together with (-)-hyoscyamine, (-)-norhyoscyamine, (-)-norscopolamine, hydroxy-6-(-)-hyoscyamine and meteloidine. Although also atropine ((±)-hyoscyamine) often has been reported to be present in Datura, it is very unclear whether it is really a natural product or an artefact obtained during isolation. Simply choosing different conditions throughout alkaloid extraction procedures (e.g. using sodium hydroxide instead of ammonia) can easily cause (-)-hyoscyamine to racemize into atropine.

Atropine, (-)-hyoscyamine and (-)-scopolamine are anti-cholinergics (parasympatholytics); they have been the starting point from which synthetic organic chemistry has created several other anti-cholinergics. Although (-)-hyoscyamine has a stronger activity than racemic atropine (the (+)-isomer is not active), the latter is more commonly prepared and used. These compounds act by competitively and reversibly inhibiting of the transmitter acetylcholine from binding to its (muscarinic) receptors, and this antagonism leads to sympathomimetic-like effects in the organs. They increase the heart rate by suppressing vagal inhibition, induce relaxation and motor inhibition in the smooth muscle fibres, decrease secretions, and induce passive mydriasis in the eyes which is very characteristic. Although at low doses their action tends to be depressant and sedative, at high doses they cause substantial excitation: agitation, disorientation, exaggerated reflexes, hallucinations, delirium, mental confusion and insomnia. (-)-Scopolamine has a similar activity, but less marked, especially on the myocardium. It potentiates neuroleptics, improves Parkinsonism, and at high doses causes speech and locomotor difficulties, affects intellectual faculties, and may lead to coma. Datura is also toxic to animals such as cattle, sheep and goats. The main clinical signs are disturbances in locomotion, fasciculation, hyperaesthesia, rapid respiration and reduced water intake.

D. stramonium has been tested for its ability to control pests, for which purpose D. metel is sometimes already used successfully.

Adulterations and substitutes

Tropane alkaloids similar to those found in Datura are known from numerous Solanaceae (e.g. hyoscyamine and scopolamine in Atropa belladonna L. and Hyoscyamus niger L.). Scopolamine is found in high quantity in Duboisia spp., which are used for industrial production in Australia.

Description

Annual herbs or short-lived perennials up to 2 m tall; stem dichotomously branched.
Leaves alternate, simple, often with oblique base, entire to repand, variously toothed or lobed, petiolate, exstipulate.
Flowers solitary in the branch forks, erect, large, bisexual, regular, usually 5-merous, shortly pedicelled; calyx tubular, circumscissile near the base after anthesis, lobed, base accrescent; corolla funnel-shaped or trumpet-shaped, lobes short, plicate and twisted in bud, with distinct acumens, sometimes appearing 10-lobed because of the presence of interacuminal lobules, white, yellow, purplish or violet; stamens adnate to the lower third of the corolla, anthers narrowly ellipsoid, basifixed, dehiscing longitudinally; ovary superior, 2-locular, often 4-locular at base because of a false septum, style filiform, stigma saddle-shaped and 2-lobed.
Fruit an ovoid to globose capsule, 2-4-celled, with slender to stout spines, frilled at the base by the calyx base, dehiscent by 4 valves from the apex or breaking irregularly, green but becoming brown, many-seeded.
Seeds almost D-shaped, compressed, testa finely pitted to coarsely sculptured, usually with well-developed funicular caruncle; endosperm present; embryo curved.
Seedling with epigeal germination; hypocotyl long and slender; epicotyl growing straight upward between the narrowly ovate, petiolate cotyledons; first 2-5 leaves smaller than subsequent ones.

Growth and development

The vegetative axis is restricted to the basal portion of the plant, and branching is restricted to the flowering part which forms the major part of the plant and which does not revert to vegetative growth. The flowers are closed during the day and open in the evening, and are reported to be pollinated by hawkmoths and to be largely self-fertile.

In studies in India it was found that mature leaves of about the middle of the stems of D. metel had the maximum alkaloid content, and that very young fruits possessed a higher content of alkaloids than later developmental stages of the fruit. In D. metel grown experimentally in Iran, the highest scopolamine concentrations were found in the roots (0.2%) of 16-week-old plants, and in the stems (0.3%) and young leaves (0.25%) of 6-week-old plants.

It is known that the hyoscyamine/scopolamine ratio in D. stramonium is influenced by the developmental stage reached by the plants. In younger plants scopolamine is the main alkaloid, whereas hyoscyamine mostly becomes the dominant alkaloid when flower development has started. It is known that alkaloids are produced in the roots and transferrred to the leaves, flowers and finally the fruits.

Other botanical information

Brugmansia is considered here as a separate genus, although it is often treated as merely a section of Datura (sect. Brugmansia (Persoon) Bernh.). It mainly differs in its habit (a woody, comparatively long-lived arborescent shrub or small tree), its mode of growth (reproducing vegetatively by root suckers), its pendulous or inclined flowers open throughout anthesis for 4-6 days with spathe-like, not circumscissile calyx and long pedicel, and its fruit being a usually indehiscent berry with unarmed pericarp. Chemically, Datura and Brugmansia are similar, and consequently they have similar medicinal applications. However, the primary use of the Brugmansia species is as an ornamental.

D. metel is easily confused with other Datura species, especially D. inoxia Miller and sometimes also D. stramonium, but is characterized by the very short spines on the fruit and the glabrous stem and leaves. There is some evidence that D. inoxia can be successfully cultivated in the Philippines; it is a source of scopolamine and can be useful as antispasmodic, and is an important medicinal plant, for instance in India.

Ecology

Datura species are usually found in more open locations: in grassland, roadsides, waste places, scrub vegetation and open forest. They tolerate various soil types but prefer clayey or loamy soils. D. stramonium can be a serious weed, e.g. in soya bean. The total alkaloid content of D. metel has been shown to peak in the hot and dry season in Nigeria, and it was lowest in the rainy season.

Propagation and planting

D. metel is generally cultivated from seed sown either directly in the field or in a nursery bed. Soaking seed for one night in water may improve germination. Per hectare, 7-8 kg of seed is needed. Seed starts germinating after about 2 weeks, and germination is complete after one month. If the seed is sown in the nursery, seedlings are transplanted when 8-12 cm tall. Effective means of vegetative reproduction, such as root suckers in Brugmansia, are absent in Datura. Normal spacing is 70-100 cm.

In vitro production of active compounds

Tropane alkaloids are biosynthesized in cell suspension cultures of D. stramonium in shake flasks and bioreactors. Calluses have been induced from leaves, stems and roots and cultured on Gamborg's B5 or Murashige and Skoog medium supplemented with growth regulators. The highest alkaloid content was produced in leaf calluses grown on a medium with low concentrations of growth regulators (0.1 mg/ml of benzyladenine and 2,4-D), and in cultures grown in the dark. In tests, the cell structures responded very well to elicitors in the late exponential phase, whereas addition of cell-wall fragments of Phytophthora megasperma enhanced the final tropane alkaloid yield by 5-fold compared with the control culture. Supplying carbon and nitrogen to cell cultures in the early stationary phase suppressed tropane alkaloid production at comparatively low C:N ratio, but at a C:N ratio of over 100 the final product yield was increased. Total alkaloid production in the cell culture supplemented with phenylalanine and ornithine was 5 times higher than in the control culture, and higher ratios of tropine to tropic acid also stimulated alkaloid production (at a ratio of 20, the productivity was 7 times higher than that in the control culture). A hyoscyamine production of up to 7.5 mg/l daily was recorded in root cultures on full-strength Gamborg's B5 medium containing 5% sucrose at 20-25 °C.

Husbandry

The application of a nitrogenous fertilizer increases both growth and the hyoscyamine content of Datura spp. As the scopolamine content is inversely related to the increase in biomass, fertilization results in accelerated decrease in scopolamine, which is the major alkaloid in young plants. Methods leading to a retarded growth by e.g. indirect sowing or thinning will lead to a retarded shift of the hyoscyamine/scopolamine ratio to hyoscyamine. However, experiments in Burundi with D. stramonium showed that the application of chemical fertilizer but also of manure, resulted in increased production of total alkaloids. As a result of experiments in Burkina Faso, deflowering was recommended to increase the total alkaloid content in the leaves.

Diseases and pests

Datura spp. can be infected by wilt and root rot caused by Sclerotium rolfsii, root and foot rot caused by Corticium solani, leaf spot caused by Alternaria spp., and by several mosaic and other virus diseases with symptoms like leaf curl, retarded growth and yellowing of leaves. Some of these diseases can be transmitted to solanaceous crops like tomato.

Harvesting

The aerial parts are usually harvested at the beginning of flowering. Plants regrow after the first harvest and can be harvested once or twice again within the same season. In experiments in Burundi it was demonstrated that the best time for harvesting leaves of D. stramonium was 8 weeks after sowing, because alkaloid content was then maximal. From experiments in Burkina Faso, it was recommended to harvest the leaves in the early morning or late afternoon.

Yield

In India, yields per ha of 10.5-14.5 t of fresh plant material and 750-1200 kg of seed of D. metel have been reported. In Pakistan, 400 kg/ha of seed of D. stramonium were harvested. Studies in Turkey showed leaf yields as high as 50 t/ha. The highest yields of scopolamine and hyoscyamine from D. stramonium reported for Algeria were 7.5 kg/ha and 21 kg/ha, repectively.

Handling after harvest

The foliage of Datura spp. is dried in the shade immediately after harvesting. The fruits are first left in the sun to dry until they are open, then threshed to remove the seeds, which are subsequently sun-dried. Dried leaves and leaf powder should be stored in well-closed containers protected from light and moisture.

Genetic resources and breeding

Both D. metel and D. stramonium have an extremely wide geographical distribution and prefer anthropogenic habitats. Therefore, they are not easily liable to genetic erosion. The genetic base of D. stramonium in South-East Asia is probably rather small because it only occurs very locally in Java. In order to develop industrial plantations for alkaloid extraction, breeding should particularly focus on high alkaloid content, combined with the development of proper means of vegetative propagation.

Prospects

Although the tropane alkaloids scopolamine, hyoscyamine and atropine can be prepared synthetically, it is more economical to extract them from plants such as Datura spp. However, Atropa and Duboisia species are the major sources of raw materials. Moreover, local demand in South-East Asia for the pure chemicals is too small to justify commercial production of Datura spp. It is likely that local demand for Datura will be for tincture production only. On the world market for the pure tropane alkaloids, it will be difficult to compete with producers in China and India.

Literature

Afsharypuor, S., Mostajeran, A. & Mokhtary, R., 1995. Variation of scopolamine and atropine in different parts of Datura metel during development. Planta Medica 61(4): 383-384.
Avery, A.G., Satina, S. & Rietsema, J. (Editors), 1959. Blakeslee: the genus Datura. The Ronald Press Company, New York, United States. 289 pp.
Backer, C.A. & Bakhuizen van den Brink Jr., R.C., 1965. Flora of Java. Vol. 2. Noordhoff, Groningen, the Netherlands. pp. 477-478.
Bruneton, J., 1995. Pharmacognosy, phytochemistry, medicinal plants. Lavoisier Publishing, Paris, France. pp. 647-667.
Demeyer, K., Vanhaste, F., van de Velde, H. & Dejaegere, R., 1990. Introductory study for the optimization of growth and alkaloid production by cell cultures of Datura stramonium L. Acta Horticulturae No 306: 210-218.
Dethier, M., Cordier, Y. & Demeyer, K., 1993. Cultivation of Datura species for scopolamine and hyoscyamine production in Burundi. Acta Horticulturae No 331: 39-48.
Gupta, S., Prabhakar, V.S. & Madan, C.L., 1973. The distribution of total alkaloids and major components in the different organs of Datura metel var. fastuosa at various stages of growth. Planta Medica 23(4): 370-376.
Hilton, M.G. & Rhodes, M.J.C., 1993. Factors affecting the growth and hyoscyamine production during batch culture of transformed roots of Datura stramonium. Planta Medica 59(4): 340-344.
International Trade Centre UNCTAD/GATT, 1982. Markets for selected medicinal plants and their derivatives. Geneva, Switzerland. pp. 103-105.
Sobti, S.N. & Kaul, B.L., 1982. Cultivation of Datura innoxia and D. metel in India. In: Atal, C.K. & Kapur, B.M. (Editors): Cultivation and utilization of medicinal plants. Regional Research Laboratory, Council of Scientific and Industrial Research, Jammu-Tawi, India. pp. 259-261.

Selection of species

Authors

Sri Hartati, Imastini Dinuriah & M.M. Blomqvist