1370

12(2): Medicinal and poisonous plants 2

Voacanga Thou.

Gen. Nov. Madag.: 10 (1806).

APOCYNACEAE

x = 11; Voacanga africana: 2n = 22, Voacanga grandifolia: 2n = 22

Major species Voacanga foetida (Blume) Rolfe, Voacanga globosa (Blanco) Merr., Voacanga grandifolia (Miq.) Rolfe.

Voacanga is an Old World genus comprising 12 species of which 5 occur in Malesia. Voacanga grandifolia has the widest distribution in Malesia. The natural distribution of Voacanga havilandii Ridley is limited to north-western Borneo and Voacanga megacarpa Merr. is confined to the Philippines.

The various Voacanga species have only rather limited local use. A few of the medical applications appear to reflect the activity of the alkaloids present in the plant.

Since the 1980s there has been a steady market for Voacanga seeds in Europe. From Cameroon, for example, 400 tonnes of seeds are collected and exported annually for processing in Europe.

Indole alkaloids are by far the medicinally most important compounds of Voacanga. Comparison of the alkaloid composition of the individual species is hampered by the varying detail of investigations. The various Voacanga species have many of the alkaloids in common. Voacanga africana Stapf is of local importance in traditional medicine in Africa and has been studied most extensively. The main alkaloids of the root bark are usually corynanthean-ibogan dimers, chiefly voacamine, with voacamidine and voacorine; vobtusine (a plumeran-plumeran dimer) may also be present. Among the monomers found, voacangine (an ibogan-type compound) is the most important; tabersonine (a plumeran base) has also been found. In the trunk bark, voacamine and congeners predominate; vobtusine may also be present. Voacangine and voacristine are also major constituents. The leaves contain mainly dimeric alkaloids of both the voacamine and vobtusine groups; nevertheless the monomeric plumeran base voaphylline is the main alkaloid. The alkaloid composition of the seeds is very different, and consists almost exclusively of the plumeran base (—)-tabersonine. Voacanga globosa has an alkaloid composition recognizable as that of a Voacanga. The dimer voacamine is the principal alkaloid of the root and trunk bark; plumeran-plumeran dimers related to vobtusine have also been isolated, as well as the ibogan monomer voacangine. From the root bark of Voacanga grandifolia, the plumeran-plumeran dimer voacamine has been isolated as the major alkaloid, together with voacamine and voacangine. From the leaves chiefly vobtusine has been isolated with only traces of voacamine. Yield of alkaloids from the fruits is low, with vobtusine as the principal base and small amounts of akuammidine and tabersonine. From the bark of Voacanga megacarpa, vobtusine and voacamine have been isolated.
The alkaloids remaining after crystallization of the tabernaemontanine fraction obtained from the stem bark of Voacanga globosa show activity against L-1210 lymphoid leukaemia and Ehrlich ascites tumour cells; tabernaemontanine itself is inactive. Tabernaemontanine causes peripheral vasodilation in chloralozed dogs; it is claimed to be of use when given orally in certain geriatric conditions (arteriosclerosis, cerebral trauma, peripheral circulatory irregularities). Tabersonine is only slightly toxic. It has about a quarter of the hypotensive activity of reserpine, and a spasmolytic effect on the smooth muscle of the intestine. It has no tumour inhibiting activity. High doses of voacangine bring about convulsions and asphyxia. Voacangine exhibits some cataleptic activity. In regular doses, voacangine has anticonvulsant activity, increases hexobarbital sleeping time in mice and decreases body temperature. In addition, it has hypotensive properties, causes bradycardia and has local analgesic activity. The hydrochloride salt of voacangine has significant diuretic activity.
Most of the pharmacological work on voacorine, voacamine and its sulphate has focused on their cardiotonic properties. Voacamine and its sulphate show little tendency to accumulate. The camphorsulphonate salt of voacamine is 1.5—2 times less toxic than the sulphate and its cardiotonic effect on the rabbit auricle 4 times stronger. Like the base, the camphorsulphonate has a direct effect on the myocardium, which is also found in situ. The cardiotonic effects of voacamine sulphate are greatly reinforced in the presence of theophylline; in the same way, simultaneous administration of strophanthin enables the dose of voacamine to be much reduced. Voacamine sulphate resembles ouabain and other cardiac glycosides in its actions on the fatigued frog heart, and there is a progressive increase in the heartbeat back to normal. When tried clinically on several patients with chronic cardiac insufficiencies of various origins, there was considerable improvement in clinical status and in haemodynamic parameters; again there was little effect on the heart rate. The alkaloid was effective both orally and intravenously. In high doses both voacamine and voacorine are hypertensive, due largely to peripheral vasoconstriction. The compounds also have parasympatholytic and sympatholytic properties, bringing about contraction of smooth muscle fibres, and they are also central nervous system (CNS) depressants. Finally, voacamine sulphate has very weak analgesic properties.
Voacamine, voacorine and voacamidine are all cytotoxic in the P-388 cell-culture system. In experiments with rats and mice parenteral and oral administration of voacamine, voacorine and voacamidine slows the growth of transplanted and primary induced neoplasms. Vobtusine is a cardiac depressant, and it causes hypotension as a result of peripheral vasodilation and a direct action on the heart. In moderate doses initial agitation is followed by a sedative effect; high doses may bring about convulsions and death. Therefore it is of no clinical interest.
Tabersonine, the major alkaloid from the seeds is readily converted to vincamine and vincamine derivatives. This is one of the principal reasons for the interest in the alkaloids from Voacanga, since vincamine has some protective action in brain ischaemia. The compounds have been shown to improve performance in animal models of cognitive dysfunction produced experimentally by hypoxia, cerebral ischaemia, and amnesia producing agents.
Finally, aqueous extract of the root bark of Voacanga africana shows antibacterial activity, anti-amoebic activity against Entamoeba histolytica and antispasmodic activity on the guinea-pig ileum. This triple action may well explain its traditional use as an antidiarrhoeal.

Plants producing alkaloids of the ibogan and bis-indole type are mostly confined to closely related genera of the tribe Tabernaemontaneae (e.g. Tabernaemontana), with the exception of e.g Catharanthus roseus (L.) G. Don.

Shrubs or trees, repeatedly dichotomously branched and with 2 inflorescences in the forks when flowering, bark usually with some latex. Leaves opposite, simple, those of a pair equal or unequal, elliptical or obovate, base cuneate or decurrent; usually petiolate, base of petioles connate into a short ocrea, with a single row of colleters in the axils. Inflorescence usually long-pedunculate, cymose, usually fairly lax. Flowers actinomorphic, 5-merous, often fragrant, calyx campanulate to cylindrical, lobes subequal, corolla twisted, tube usually shorter or only slightly longer than calyx, usually creamy or yellow, lobes in bud overlapping to the left, spreading or recurved; stamens 5, exserted or included; ovary superior, usually broadly ovoid, pistil glabrous. Fruit consisting of 2 free or less often partly or completely united carpels, usually many-seeded. Seed surrounded by a yellow or orange pulpy aril, endosperm copious, starchy, creamy to white, ruminate, surrounding the spathulate creamy to white embryo.

The South-East Asian Voacanga species appear to flower and fruit throughout the year.

Voacanga belongs to the tribe Tabernaemontaneae of the subfamily Plumerioideae. It is closely related to Tabernaemontana. In Malesia, Voacanga can easily be distinguished by the pistil head, style and calyx being shed with the corolla, whereas the calyx is persistent in Tabernaemontana, even in fruit.
Voacanga africana is of local importance in traditional medicine in West, Central and East Africa. Various parts of the plants are used in numerous kinds of preparations, applied externally and internally, for skin afflictions, ophthalmia, diarrhoea, oedema, afflictions of the urogenital system, rheumatism, and also as a vermifuge and general tonic.

The Malesian Voacanga species occur in light forest or secondary vegetation, often along rivers.

Leaf-cell suspension cultures of Voacanga africana, grown for 20 days under standard conditions, yielded 6 alkaloids. (—)-Tabersonine, lochnericine and (—)-minovincinine were the major alkaloids. Voafrine A and B, plumeran-plumeran dimers not previously detected from nature were also produced. Voafrine A and B are of pharmacological interest due to the activity of the related compound vincaleucoblastine. This alkaloid composition approaches most nearly that of the seeds.

Fruits of Voacanga are collected when mature. Bark should preferably be collected at the end of the growing season in view of the higher alkaloid content. Roots are simply unearthed to obtain the root bark.

The content and composition of alkaloids in leaves and bark of Voacanga varies seasonally. In seasonal climates contents are highest at the end of the growing season, e.g. November in India. With respect to alkaloid concentration in the leaves in November, an increase from 1% for those at the first to 2.2% at the 6th node (25 days old) and a steady decline at older nodes was observed.

Fruits of Voacanga are dried and seeds subsequently removed, or seeds are removed prior to drying. Dried seeds are pulverized and the powdered material is usually subjected to extraction by standard methods for alkaloids. Other more sophisticated methods have also been patented. Trunk bark, after being removed in strips, is dried. Patented extraction procedures have been developed to obtain cardioactive components from the bark.

The apparent tolerance of Voacanga for disturbed habitats lowers the risk of genetic erosion. Except for some occasional representations in botanical gardens no germplasm collections or breeding programmes are known to exist.

Many of the indole alkaloids found in Voacanga display very distinct and interesting pharmacological activities. Some of them have the potential to be excellent candidates for lead compounds in the development of future medicines. Much research has been done already, however, much more will be needed in future to fully exploit their possibilities.

Bisset, N.G., 1985. Phytochemistry and pharmacology of Voacanga species. Series of revisions of Apocynaceae XV. Agricultural University Wageningen Papers 85-3. pp. 81—113.
Bisset, N.G., 1985. Uses of Voacanga species. Series of revisions of Apocynaceae XV. Agricultural University Wageningen Papers 85-3. pp. 115—122.
Gutierrez, H.G., 1980. An illustrated manual of Philippine materia medica. Vol. 1. Natural Research Council of the Philippines, Tagig, Metro Manila, the Philippines. pp. 40—41.
Leeuwenberg, A.J.M., 1985. Voacanga Thou. Series of revisions of Apocynaceae XV. Agricultural University Wageningen Papers 85-3. pp. 5—80.
Tona, L., Kambu, K., Mesia, K., Cimanga, K., Apers, S., De Bruyne, T., Pieters, L., Totte, J. & Vlietinck, A.J., 1999. Biological screening of traditional preparations from some medicinal plants used as antidiarrhoeal in Kinshasa, Congo. Phytomedicine 6(1): 59—66.

R. Hendrian

Voacanga foetida
Voacanga globosa
Voacanga grandifolia

Hendrian, R., 2001. Voacanga Thou.. In: van Valkenburg, J.L.C.H. and Bunyapraphatsara, N. (Editors): Plant Resources of South-East Asia No 12(2): Medicinal and poisonous plants 2. PROSEA Foundation, Bogor, Indonesia. Database record: prota4u.org/prosea

The following species in this genus are important in this commodity group and are treated separatedly in this database:
Voacanga foetida
Voacanga globosa
Voacanga grandifolia