Strychnos (PROSEA)

Plant Resources of South-East Asia Introduction

List of species

Strychnos L.

Protologue: Sp. pl. 1: 189 (1753); Gen. pl. ed. 5: 86 (1754).

Family: Loganiaceae

Chromosome number: x= unknown; S. ignatii: 2n= 44, S. nux-vomica: 2n= 44

• Strychnos ignatii Bergius,
• S. nux-vomica L.

• Malaysia: akar ipoh.

Strychnos consists of 150-200 species and is distributed throughout the tropics and subtropics. Approximately 25 species occur in the Malesian region.

The seeds, bark, wood and roots (e.g. of S. ignatii and S. nux-vomica) had or have numerous applications in traditional medicine. Strychnos was already being used medicinally in China in the 14th Century. It has been prescribed as a stomachic, febrifuge, vermifuge, anticholeric and tonic and to treat sores, wounds, eczema and snake bites in Indonesia and the Philippines. In India, the seeds have been used to obstinate vomiting, to treat cholera, diarrhoea, asthma, dropsy, rheumatism, paralytic and neuralgic affections, spermatorrhoea, epilepsy, diabetes, anaemia and chlorosis, and as a tonic, febrifuge and vermifuge, and to treat alopecia. In Australia, the fruit pulp of S. lucida has been used to treat a variety of skin complaints. S. wallichiana Steudel ex DC. (synonym: S. gautheriana Pierre ex Dop p.p.) is used in traditional medicine in Vietnam to treat rabies, leprosy, and as an aphrodisiac. S. potatorum L. is used in both the Ayurvedic and Yunani systems of medicine in India where its bark is used to adulterate S. nux-vomica bark and its seeds are used as a natural coagulant to purify drinking water. Several Strychnos species are used medicinally in Africa and South America.

Strychnos has also been used as an ingredient in tonic preparations, but these are no longer used in modern therapy, except for a few rare proprietary products based on "nux vomica" tincture (from S. nux-vomica) or Saint Ignatius beans (seeds of S. ignatii).

In general, all preparations containing Strychnos should be used in small doses, and with the greatest caution, because of their toxicity.

Strychnine was formerly used mainly to poison rodents. The drug was introduced in Europe as long ago as the 16th Century to eliminate pests.

S. axillaris Colebr. has apparently been used in Peninsular Malaysia in the preparation of arrow poison; its leaves have been used in India as a suppurative and the seeds internally as a febrifuge. The root bark of S. vanprukii Craib has been reportedly used to prepare an arrow poison in Peninsular Malaysia; S. rufa C.B. Clarke has been used similarly.

In Borneo and other regions Strychnos seeds, bark and roots are used for making dart poison for blowpipes, usually in combination with the sap of Antiaris toxicaria Lesch. In South America, Strychnos (mainly S. castelnaei Wedd., S. guianensis (Aubl.) Mart. and S. toxifera Schomb. ex Benth.) is used to prepare the so-called gourd or calabash curare. Tube (or bamboo) curare is made from lianescent Chondrodendron species (C. tomentosum Ruiz & Pavon). Both curares, alone or as a mixture, are used as arrow poison.

The stems of lianescent species are used for rough cordage. The wood of species with a tree habit is occasionally used for implements and cabinet work.

The annual production of S. nux-vomica seed in India was estimated at 2000 t at the beginning of the 1970s. In the period 1965-1971 the average production of strychnine and brucine from S. nux-vomica seeds in India was 18 000 kg/year. Most of the alkaloids are exported to the United States and Europe.

The drug usually consists of dried seeds. The seeds of S. nux-vomica contain 1-3% total alkaloids (of the indole type; biosynthetically derived from tryptophan), chiefly represented by strychnine (1.1-1.5(-2.3%)) and its dimethoxylated derivative brucine (1.1-2.1(-3.6%)). Bark, wood, roots and flowers also contain these compounds, but with strychnine in smaller amounts. Wood collected from S. lucida in Java during the rainy season showed a higher alkaloid content than that of wood harvested in the dry period of the year. Several minor alkaloids, with closely related structures, have also been isolated from S. nux-vomica seeds (total concentration up to 1%): 12-hydroxy-strychnine, 15-hydroxy-strychnine, α-colubrine, β-colubrine, icajine, 11-methoxy-icajine, novacine, vomicine, pseudostrychnine, pseudobrucine, pseudo-α-colubrine, pseudo-β-colubrine, N-methyl-sec-pseudo-β-colubrine and isostrychnine.

The seeds of S. ignatii contain 1.5-2% of strychnine, 0.5% of brucine and the minor related alkaloids 12-hydroxystrychnine, α-colubrine, icajine, novacine and vomicine. Small amounts of berberine (an isoquinoline alkaloid) have also been reported. The major alkaloid in the wood of S. lucida is brucine. The bis-indole alkaloid longicaudatine has been isolated from several Strychnos spp., including S. ignatii and S. nux-vomica. This compound has strong reserpine-like activity.

Strychnine is a very toxic alkaloid. The lethal dose in adult humans may start at about 0.4 mg/kg. In small doses the compound produces excitation of all parts of the central nervous system. It acts as a competitive inhibitor of the neurotransmittor glycine at its receptor-binding site located at the Renshaw cells in the spinal cord. By binding, strychnine blocks the normal inhibitory action of glycine and the Renshaw cells on the motor-neurons, thus leading to a spread of motor-cell stimulation. Intoxication may cause anxiety, increased sensitivity to noise and light and periodic convulsive attacks: all the muscles contract, forcing the patient into a position, with the back arched and resting only on the head and heels. Death may occur by asphyxia following the contraction of the diaphragm. Brucine is less active as a poison; about 50-100 less than a comparable dose of strychnine.

Strychnine and brucine can be distinguished by thin-layer chromatography of e.g. a macerate of the simplex in 70% ethanol. Quantification can be achieved by spectrophotometry on an alkaloid extract; the difference between the absorbances at 258 nm (λ^max of strychnine) and 300 nm (λ^max of brucine) is taken into account. Reversed-phase HPLC procedures for qualitative and quantitative analysis, and more recently a capillary zone electrophoresis method for quantitative estimation of strychnine and brucine in S. nux-vomica seeds are also available. According to the Netherlands Pharmacopoeia VI, for the drug to be of good quality the strychnine concentration should not be less than 1%.

Some alkaloids from African Strychnos species have shown potential as anti-cancer agents in animal tests, and also anti-amoebic and anti-plasmodial activity in mice. Alkaloids isolated from South American Strychnos have demonstrated a wide anti-microbial spectrum.

Galactomannans and galactans have been demonstrated in the seeds of S. nux-vomica. These polysaccharides, which have coagulant properties, are also present in the seeds of the Indian S. potatorum. The seed extract is efficient in the coagulation-flocculation of hydrophobic colloids (such as a clay suspension), but it is a poor flocculant in the case of hydrophilic colloids (such as bacteria). The seed extract of S. nux-vomica exhibits analgesic, anti-ulcer, cytotoxin and uterine stimulant activity.

Aqueous and ethanolic extracts of Strychnos leaves showed antifungal activity against several pathogens of rice in India.

As well as occurring in Loganiaceae, monoterpenoid indole alkaloids also occur particularly in Rubiaceae (e.g. Cinchona, Uncaria) and Apocynaceae (e.g. Catharanthus, Rauvolfia, Voacanga). Several species from these families and genera have uses comparable to Strychnos.

• Lianas or sometimes shrubs (often scrambling) to treelets; stem usually with axillary simple or double tendrils, sometimes with axillary thorns.
• Leaves opposite, simple and entire, and except for the midrib having 1-2(-3) pairs of nearly equally strongly developed basal veins which do not fully reach the leaf apex; petiole mostly inserted upon distinct leaf-cushions; stipules reduced to a mostly ciliate and straight rim connecting the leaf bases.
• Inflorescence terminal or axillary, thyrsoid; bracts scale-like.
• Flowers bisexual, actinomorphic, (4-)5-merous; calyx divided nearly to the base, lobes ciliate on the margins, brown; corolla gamopetalous, rotate to salver-shaped, sometimes thickened towards the lobes, white to yellowish or greenish, lobes valvate in bud, spreading to reflexed, tube usually densely papillose outside, variably hairy inside; stamens inserted on the corolla tube alternating with the lobes, exserted, anthers basifixed, longitudinally dehiscent, introrse; ovary superior, 2-celled, style cylindrical, stigma faintly 2-lobed.
• Fruit a globose or ellipsoid berry, with hard shell, smooth or minutely warty, glabrous, orange to red when ripe, with fleshy, usually orange pulp, 1-many-seeded.
• Seeds lenticular, orbicular to ellipsoid, often convex on one side and concave on the other side, with a silky or felty testa or glabrous; endosperm copious, bony; embryo minute, straight, with small cotyledons.
• Seedling with epigeal germination; cotyledons emergent, thin and leaf-like, long persistent; hypocotyl long.

The flowers of Strychnos are pollinated by insects. Mammals (e.g. monkeys and civet-cats) and birds digest the fruit pulp and disperse the seeds.

Flowers are essential when identifying Strychnos species. Fruits and seeds are also characteristic features of Strychnos species and should be kept in spirit (when collecting herbarium material) to preserve important characters that will disappear upon drying.

Most Strychnos are large lianas of the forest, but a few are scrambling to erect shrubs or small to medium-sized trees occurring in more open habitats (e.g. S. lucida).

In India, S. nux-vomica plants have been successfully regenerated from hypocotyl tissue. Seeds were germinated on Murashige and Skoog medium supplemented with 1 mg/l gibberellic acid, and hypocotyls excised from the resulting seedlings were inoculated on Murashige and Skoog medium. The optimal growth of plantlets occurred when the medium was supplemented with 2 mg/l kinetin and 1 mg/l naphthalene acetic acid. In vitro multiplication was also successful using nodal explants excised from healthy mature trees.

Leaf galls induced by the jumping plant louse Diaphorina truncata have been reported for S. nux-vomica in India, resulting in abscission of the leaves.

Fruits of S. nux-vomica are usually gathered from the trees. Fallen fruits are considered to be of inferior quality.

After collecting, seeds of Strychnos are cleaned and dried in the sun. Dried seeds can be stored in jute bags for a long period without any loss of alkaloidal content, but they should be kept in dry conditions to prevent deterioration by fungi such as Aspergillus and Penicillium species. Seeds are further processed in factories to obtain strychnine and brucine.

In traditional Chinese medicine, seeds of S. nux-vomica are usually processed to reduce their toxicity. Sand or sesame oil is heated in an iron pan up to 235°C and seeds are parched for about 3 minutes. This significantly reduces the contents of strychnine, brucine and β-colubrine and increases the amounts of isostrychnine, isobrucine, strychnine N-oxide and brucine N-oxide.

The Strychnos species mentioned have a large area of distribution and are, at least locally, common. They are too little used to be threatened at present. However, forest destruction may easily endanger Strychnos spp. with a narrow distribution. S. nux-vomica is widespread in India, Indo-China and Thailand, but is rare in the Malesian region. There are no records of Strychnos in germplasm collections.

The importance of Strychnos as a medicinal plant and vermin destroyer has diminished in recent years. It is now hardly used in modern phytotherapy. Some of the alkaloids present in the plants may play a role in the development of new anti-cancer or antimalarial drugs, but research is needed to establish the possibilities.

• Bisset, N.G., 1974. The Asian species of Strychnos. Part III. The ethnobotany. Lloydia 37(1): 62-107.
• Bisset, N.G. & Phillipson, J.D., 1976. The Asian species of Strychnos. Part IV. The alkaloids. Lloydia 39(5): 263-325.
• Bruneton, J., 1995. Pharmacognosy, phytochemistry, medicinal plants. Lavoisier Publishing, Paris, France. pp. 829-830.
• Cai, B.-C., Hattori, M. & Namba, T., 1990. Processing of nux vomica. II. Changes in alkaloid composition of the seeds of Strychnos nux-vomica on traditional drug-processing. Chemical and Pharmaceutical Bulletin 38(5): 1295-1298.
• Corsaro, M.M., Giudicianni, I., Lanzetta, R., Marciano, C.E., Monaco, P. & Parrilli, M., 1995. Polysaccharides from seeds of Strychnos species. Phytochemistry 39(6): 1377-1380.
• Council of Scientific and Industrial Research, 1976. The wealth of India: a dictionary of Indian raw materials & industrial products. Vol. 10. New Delhi, India. pp. 61-68.
• Kopp, B., Bauer, W.P. & Bernkop-Schnürch, A., 1992. Analysis of some Malaysian dart poisons. Journal of Ethnopharmacology 36(1): 57-62.
• Kumar, A. & Datta, S.K., 1989. Plantlet regeneration from hypocotyl tissue of Strychnos nux-vomica Linn. Current Science 58(14): 812-813.
• Leenhouts, P.W., 1962. Loganiaceae. In: van Steenis, C.G.G.J. (General editor): Flora Malesiana. Series 1, Vol. 6. Wolters-Noordhoff Publishing, Groningen, the Netherlands. pp. 343-361.
• Massiot, G. et al., 1983. Occurrence of longicaudatine, a new type of bis-indole base and bisnor-C alkaloid H in Strychnos spp. Journal of Organic Chemistry 48(11): 1869-1872.

• Strychnos ignatii
• Strychnos lucida
• Strychnos minor
• Strychnos nux-vomica

• Purwaningsih