Thevetia peruviana (PROSEA)

Plant Resources of South-East Asia Introduction

List of species

Thevetia peruviana (Pers.) K. Schum.

Protologue: Engl. & Prantl, Nat. Pflanzenfam. 4(2): 159 (1895).

Family: Apocynaceae

Chromosome number: 2n= 20

Synonyms

• Cerbera peruviana Pers. (1805),
• Thevetia nereifolia Juss. ex. Steud. (1841),
• Cascabela thevetia (L.) Lippold (1980).

Vernacular names

• Yellow oleander, lucky nut tree (En).
• Oléandre jaune (Fr)
• Indonesia: ginje, ki hujan (Sundanese)
• Malaysia: tevetia peru
• Philippines: campanero, campanilla (Tagalog)
• Thailand: sae nawa (northern), ban buri (Bangkok), ram phoei (central)
• Vietnam: thông thiên, huỳnh liên.

Origin and geographic distribution

T. peruviana originates from tropical America and is widely cultivated in South-East Asia as an ornamental.

Uses

T. peruviana is widely used in folk medicine in Central and South America. The uses recorded for South-East Asia are similar. In the Philippines and India it has become a household remedy for several ailments. A decoction prepared from the bark or leaves is applied in regulated doses to loosen the bowels, as an emetic, and is said to be an effective cure for intermittent fevers. The seeds may be used as a purgative in rheumatism and dropsy. A decoction of the seeds acts as a violent emetic, hinders respiration, and may cause paralysis of the heart. Pulverized seeds are sometimes an ingredient of suppositories to alleviate haemorrhoids. The roots are made into a plaster which is applied to tumours. However, care should be taken in all medical applications, in particular those used internally, as high dosage may result in poisoning. In Vietnam, purified thevetin is employed as a cardiotonic. In Thailand and India, the oil from the kernel is applied topically to treat skin complaints. In India, seeds have been used for committing suicide or homicide. Other reports state its use as abortifacient. The kernels act as a contact poison; mashed with a soap solution they are used as an insecticide. The wood may be employed as fish poison.

Production and international trade

Yellow oleander is usually cultivated in home gardens for use in local medicine and as an ornamental. The plants do not enter the international trade.

Properties

All parts of T. peruviana produce latex which is highly poisonous; the kernels are the most toxic. The active principles are cardiac glycosides of the cardenolide type. The toxic manifestations of yellow oleander-poisoning mainly involve the cardiovascular system (including various types of arrhythmia, e.g. sinus bradycardia) and the gastro-intestinal tract. Vomiting is the common symptom in poisoning in about 30% of all cases. Ischaemic changes occur in about 40% of the cases, as well as palpitations in about 10%. The most serious and immediate cause leading to death is peripheral vascular failure: of the 14 autopsied death cases all showed subendocardial and perivascular haemorrhage with focal myocardial oedema.

The cardiac glycosides of T. peruviana are triosides or monosides, i.e. they contain an aglycone unit combined with 3 or 1 sugar moieties, respectively. The aglycones of these glycosides are either digitoxigenin, or the related cannogenin (the 19-oxo form of digitoxigenin) or cannogenol (the 19-oxy form of digitoxigenin). Thevetin, is the major component of the seeds. It was subsequently found to be a mixture of 2 tiosides, cerberoside (= thevetin B) and thevetin A in a 2:1 ratio. A small portion of 2'-O-acetyl cerberoside is also associated with thevetin.

The monosides separated from the seeds include neriifolin, cerberin (= 2'-O-acetylneriifolin), peruvoside, theveneriin (= ruvoside) and perubosidic acid (perusitin).

Of all the Thevetia cardiac glycosides, peruvoside has been investigated most thoroughly. Preliminary work on the cardiotonic effect showed that it exerts a quick and powerful positive inotropic effect in experimental animals, comparable to that of ouabain. In therapeutic doses, peruvoside produced a fall in right atrial pressure, and a rise in the cardiac output. Furthermore, it was found that peruvoside inhibited Na⁺,K⁺-ATPase activities and that it showed a strong competitive inhibition on (³H)-ouabain binding to this enzyme isolated from various tissues. A marked difference in reponse of experimental animals was found which was as great as that of Digitalis. The inhibitory effects on the enzyme activity were stronger than the positive inotropic effect, while these effects of Digitalis were parallel quantitatively.

The first clinical trials with peruvoside were carried out on cases of congestive cardiac failure. Oral administration of the drug produced digitalization in all patients. Since then, clinical testing of peruvoside has been undertaken at a large number of centres, particularly in India and Germany. Large-scale clinical trials with 1600 patients showed that all forms of cardiac insufficiency can be successfully treated with peruvoside, and compensation can be maintained during continuous therapy in about 85% of the patients. Special indications include cardiac insufficiency with bradycardia, latent cardiac insufficiency, insufficiency of the senile heart, and cor pulmonala chronicum. Peruvoside was also beneficial in the treatment of cardiac insufficiency subsequent to myocardial infarction. The drug was tolerated well, and possible side effects were mostly manifested in the form of gastro-intestinal symptoms of irritation.

Of the other Thevetia cardiac glycosides, the mixture thevetin is practically identical in effect with ouabain, and about one-eighth as potent (the lethal dose for a cat being 0.85 mg/kg). It has effectively been used clinically in cases of cardiac decompensation, although its effective dose is rather close to its toxic dose. Thevetin A is far less potent than thevetin, and as a cardiac glycoside the potency of neriifolin is only moderate. Finally, cerberoside (thevetin B) is one of the weakest of the Thevetia glycosides in its cardiotonic effect.

Furthermore, in screening tests against 6 pathogenic bacteria with solutions of 4 dilutions (1:100, 1:250, 1:500 and 1:1000) and with pure kernel oil, strong bactericidal activity was demonstrated, especially against Bacillus subtilis and Staphylococcus aureus. The pure oil was more effective than the control, 1000 ppm griseofulvin, against all 6 species; dilutions of 1:500 and above were generally as active as the control or more so, except against Vibrio cholerae .

Decoctions, infusions and expressions from the different plant parts did not show any direct DNA damaging capacity. They were not mutagenic before or after metabolic activation, and did not possess chromosome-breaking effects. However, decoctions from leaves and expressions from kernels and seeds exhibited antimutagenic effects in bone marrow cells of mice treated with methylmethane sulphonate, tetracycline and N-nitrosopyrrolidine.

Adulterations and substitutes

Cardiac glycosides are present in several other genera of the Apocynaceae, e.g. Cerbera (structurally very similar; cerberoside (= thevetin B) is also found in Cerbera odollam Gaertner) and Strophanthus.

Description

• A shrub or tree up to 8 m tall; branchlets glabrous, exuding white latex.
• Leaves spirally arranged, simple, linear-lanceolate, 6-15 cm × 0.4-0.7 cm, long-acuminate, venation obscure, coriaceous; petiole very short.
• Inflorescence subterminal, cymose, few-flowered.
• Flowers 5-merous, only faintly fragrant; sepals acute, spreading; corolla lobes overlapping to the left in bud, corolla infundibuliform, tube widening around the middle, about 3 cm long with densely pubescent corona lobes near the throat alternating with the stamens, lobes about 3 cm long, yellow; stamens completely included, anthers attached to each other apically across top of pistil head but not adnate to it, yellow to orange or peachy pink; ovary consisting of 2 carpels, several ovules per carpel.
• Fruit a drupe with mericarps united into an obdeltoid shape, laterally compressed, about 3-4 cm in diameter, yellowish-green turning red, ripening black, exocarp fleshy, mesocarp stony, endocarps free from each other.
• Seed flattened with a small wing, one seed per mericarp.
• Seedling with epigeal germination.

Growth and development

In areas without a seasonal climate T. peruviana flowers and fruits throughout the year. However, a peak in flowering can be observed in a particular time of the year.

Other botanical information

Thevetia comprises 8 species and originates from tropical America. Some species are widely cultivated outside this area. T. peruviana is the only species cultivated in South-East Asia. Ornamental T. peruviana with white flowers is traded as cv. "Alba".

Ecology

In its native habitat, T. peruviana is found in evergreen lowland or riparian forest from 50-200 m altitude.

Propagation and planting

In cooler climates T. peruviana can be grown as pot plants in tubs in the glasshouse or conservatory, to be moved outdoors for the summer months. Cultivars are propagated by semi-ripe cuttings of terminal shoots, or by stem sections during the growing season. Propagation by seed should preferably be done at the start of the growing season. In vitro propagation by direct shoot morphogenesis, without any intermediate callus phase is also possible. This method may be used for mass propagation of superior plant material.

Husbandry

T. peruviana is grown in full sun or light shade, in fertile, well-drained loams with additional leaf mould. The shallow-rooted plants should be protected from strong winds. Stem tips of young plants are pinched out to encourage a bushy habit, and established specimens are pruned after flowering or shortly before the growing season to shape and restrict size.

Diseases and pests

In India, infestation of T. peruviana with Cuscuta reflexa Roxb. resulted in severe suppression of young leaves, with infected leaves turning yellow and desiccating. Under glass, scale insects, mealybug, red spider mite and aphids may be pests.

Handling after harvest

Ripe fruits of T. peruviana are sun-dried and split to obtain the seeds.

Genetic resources and breeding

The widespread cultivation of T. peruviana as an ornamental diminishes the risk of genetic erosion.

Prospects

At present in medicine, cardiac glycosides are only applied in distinct, special cases. In the western world, the drug of choice is in general digoxin from Digitalis lanata Ehrhart, or in acute situations the strophanthins (e.g. ouabain) from Strophanthus spp. Therefore, the cardenolides from T. peruviana, although the pharmacological effects of peruvoside are very well documented, are unlikely to play a significant role in future medicine. In distinct cases, however, they may very well serve as a local source of cardiac glycosides, when digoxin and ouabain are not available.

Literature

• Bose, T.K., Basu, R.K., Biswas, B., De, J.N., Majumdar, B.C. & Datta, S., 1999. Cardiovascular effects of yellow oleander ingestion. Journal of the Indian Medical Association 97(10): 407-410.
• Council of Scientific and Industrial Research, 1976. The wealth of India: a dictionary of Indian raw materials & industrial products. Vol. 10. Publications and Information Directorate, New Delhi, India. pp. 226-230.
• Macesar, C.L. & Lim-Sylianco, C.Y., 1988. Genotoxic potential and antimutagenic effects of Thevetia peruviana (Pers.) Merr. Philippine Journal of Science 117(1): 55-67.
• Middleton, D.J., 1999. Apocynaceae. In: Santisuk, T. & Larsen, K. (Editors): Flora of Thailand. Vol. 7(1). The Forest Herbarium, Royal Forest Department, Bangkok, Thailand. pp. 69-70.
• Saxena, V.K. & Jain, S.K., 1990. Thevetia peruviana kernel oil: a potential bactericidal agent. Fitoterapia 61(4): 348-349.
• Ye, Y.X. & Yang, X.R., 1990. Inhibitory action of peruvoside and neriifolin on sodium potassium ATPase. Acta Pharmacologica Sinica 11(6): 491-494. (in Chinese)

Other selected sources

• Burkill, I.H., 1966. A dictionary of the economic products of the Malay Peninsula. Revised reprint. 2 volumes. Ministry of Agriculture and Co-operatives, Kuala Lumpur, Malaysia. Vol. 1 (A-H) pp. 1-1240, Vol. 2 (I-Z) pp. 1241-2444.

241, 263, 380, 407, 696, 739, 786, 810, 1070.

Authors

J.L.C.H. van Valkenburg & S.F.A.J. Horsten