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12(2): Medicinal and poisonous plants 2

Anamirta cocculus (L.) Wight & Arn.

Prodr. fl. Ind. orient. 1: 446 (1834).

MENISPERMACEAE

2n = (22), 24, 26

Menispermum cocculus L. (1753), Menispermum lacunosum Lamk (1797), Cocculus populifolius DC. (1817), Anamirta paniculata Colebr. (1822).

Fish berry, poison berry (En). Indonesia: tuba biji (general), oyod peron (Javanese), bori (N. Halmahera, Ternate). Philippines: arai (Bagobo), lagtang (Bisaya, Manobo, Sulu, Tagalog), ligtang (Tagalog). Cambodia: seg dom. Thailand: khamin khruea (northern), om phanom (south-eastern), waai din (central). Vietnam: d[aa]y t[as]o, d[aa]y d[oo]ng c[aaf]u.

Anamirta cocculus is the only species in the monotypic genus Anamirta. It occurs naturally from India, Sri Lanka, Andaman and Nicobar Islands, Thailand, Indo-China, through Sumatra, Java, Lesser Sunda Islands, the Moluccas, to the Philippines and New Guinea.

In the Philippines, an infusion of the roots of Anamirta cocculus is used to treat fevers, dyspepsia and menstrual problems. Extract of the stem is added to native wine and is drunk to make the blood strong. The leaves may be used as a poultice for headache, stomach-ache or delayed menstruation. The dried fruits constitute the drug known as 'cocculus' or 'cocculus indicus'. In Laos, the fruit is used in very small doses to treat eruptive fevers. The powdered fruit is used to treat acute barbiturate poisoning. In India, the fruits and seeds are made into an ointment for external application to treat skin diseases. The seeds are also externally applied to kill head lice. The juice of the fruits is applied externally to ulcers and scabies.
Fruits of Anamirta cocculus are officially listed in the Pharmacopoeias of various countries. The fruit and especially the seed contain picrotoxin, a very strong poison. Picrotoxin has been used intravenously as an antidote against poisoning by barbiturates and morphine. However, the safe therapeutic dose range is very narrow. Picrotoxin has been used in very minute doses as a nervine tonic in schizophrenia and epilepsy and similar afflictions.
In South-East Asia the fruit of Anamirta cocculus is used mainly as a fish poison and as an insecticide. For fish poison fresh or dry semi-ripe fruits with or without the fruit pulp are ground with shell-fish, shrimp or small crabs. The resulting paste is made into pellets used as fish bait. Upon ingestion of these pills the fish become stupefied and will float to the surface, after which the fish must be swiftly eviscerated. This is done in order to reuse the bait and avoid contamination of the fish with the poison. In the Philippines fruits are heated or roasted, crushed and powdered. The resulting powder is simply thrown in the water to stupefy the fish.
In the past the fruit was sometimes used fraudulently in the United Kingdom to flavour beers with its bitterness.
The bast-fibres are used for basketry rope and belt making.

Dried fruits of Anamirta cocculus have since long been exported from India to the Near East and Europe. They were known to the physicians of the Arabic schools from the tenth century, and in the following centuries passed on to Europe, obtaining the name 'cocci orientalis'. Recent information on production and trade, however, is not available. The fruits are an ingredient of many homeopathic formulations.

Fruits of Anamirta cocculus contain about 1.5% picrotoxin, which is also known as cocculin. Picrotoxin is a crystalline equimolar mixture of 2 sesquiterpene dilactones, i.e. picrotoxinin and picrotin. Of the latter 2, only picrotoxinin is pharmacologically active.
The seed, when taken internally, is a powerful poison for all vertebrates affecting the central nervous system, stimulating the motor and inhibitory centres in the medulla, especially the respiratory and vagus centres, acting on the heart and respiration. It also irritates motor centres, either in the cerebrum or in the medulla and cord, producing in all vertebrates alternating epileptiform spasms, with periodic stoppage of the motions of the diaphragm and slowness of the pulse. The poisoning causes vomiting, purging, profuse sweating and intoxication, with extreme giddiness, dimness of vision and unconsciousness. Breathing and the pulse become weak. The poisoning also results in clonic convulsions; during spasms and intervals of relaxations the pupils correspondingly contract or dilate. Death occurs rapidly from respiration failure, or slowly from gastro-intestinal symptoms.
On a biochemical level, picrotoxin (or more precisely its active constituent, picrotoxinin) act as GABA (gamma-amino butyric acid) antagonists. It stimulates the central nervous system, particularly the medulla oblongata and respiratory centre. Administration of picrotoxin via the vertebral artery decreased sinus rate and increased circulating levels of vasopressin. On the other hand, infusion of picrotoxin into the internal carotid artery caused increases in sinus rate, blood pressure and plasma vasopressin. These data support the hypothesis that GABAergic mechanisms at different levels of the neuraxis exert opposite effects on cardiac vagal activity, and that GABAergic mechanisms in both the brainstem and forebrain inhibit the release of vasopressins into the systemic circulation.
At receptor level, the GABA receptor is a complex, membrane-bound glycoprotein, operating a chloride-ion channel. When the endogenous agonist GABA is released into the synaptic cleft, the receptor opens its ion channel, resulting in an influx of chloride ions and hyperpolarization of the membrane, thus being responsible for the resulting pharmacological effects. On the GABA receptor site, barbiturates bind close to the chloride channel and, at least in part, increase chloride-ion conductance mimicking GABA activation. On the other hand, picrotoxinin specifically binds to the same barbiturate site, but blocks the opening of the chloride channel. Therefore, picrotoxin can be used as a specific barbiturate poisoning antagonist, although its safety limits are very narrow.
Furthermore, the fruits contain the isoquinoline alkaloids menispermine, paramenispermine, magnoflorine, stephorine, berberine, palmatine and l,8-oxotetrahydropalmatine. In addition, the stem and roots contain only small amounts (about 0.1%) of the alkaloids berberine, palmatine, magnoflorine, columbamine and l,8-oxotetrahydropalmatine. The stem also contains oxypalmine and stepharine. In general, the alkaloids isolated from Anamirta cocculus have antibacterial-, antimicrobial-, sympatholytical- (acetylcholine), and antifertility activities.

Picrotoxin is also isolated from Tinomiscium petiolare Hook.f. & Thomson (Menispermaceae). Several of the alkaloids recorded for Anamirta cocculus occur in other Menispermaceae, e.g. berberine and palmitine in Arcangelisia spp., berberine, palmitine and magnoflorine in Tinospora spp., and magnoflorine in Cyclea spp.

A large, dioecious liana, up to 15 m long; stem twisting to the left, up to 10 cm in diameter, with stout, smooth branches, young stems and petioles pale straw-coloured when drying, striate, wood white or yellowish, exuding white milky sap when cut. Leaves alternate, simple, ovate to broadly ovate, 16—18 cm x 10—24 cm, base cordate to truncate, apex shortly acuminate, margin entire, palmately 3—5(—7)-veined at base with 4—5 pairs of lateral veins running parallel with the main pair of basal veins, lower surface with reticulum clearly visible and slightly raised, midrib very prominent, glabrous on both surfaces apart from hairy patches (domatia) in the axils of the secondary and main veins, thinly coriaceous; petiole 6—8(—26) cm long, glabrous, swollen at both ends, geniculate at base; stipules absent. Inflorescence a panicle, cauliflorous, spreading or pendulous, 16—40 cm long with lateral branches 2—5 cm long, glabrous, bracteoles about 0.5 mm long. Flowers shortly pedicellate, unisexual, petals absent, strongly fragrant; male flowers with glabrous pedicels up to 2—3 mm long, sepals white, yellow or pale green, outer sepals 2, scarcely 1 mm long, inner sepals 6, broadly elliptical, 2.5—3 mm x 2 mm, glabrous apart from often minutely papillose margin, stamens 30—35, filaments more or less connate, anthers in a stalked cluster; female flowers with pedicels and sepals as in male flower, staminodes 6, carpels 3(—4), curved-ellipsoid, 1.5—2 mm long, stigma thick, recurved. Infructescence with lateral branches up to 15 cm long, gynophore (3—)6—16 mm long, shortly branched below the drupes, continuous with pedicel, 8—20 mm long. Fruit a drupe, nearly spherical, 9—11 mm long, white turning red, finally dark purple, glabrous, smooth and hard when dry. Seed deeply cup-shaped, with endosperm; embryo with foliaceous, divaricate cotyledons.

Anamirta cocculus often bears flowers in abundance, the fragrant smell can be detected by man from 50 m distance. Pollination is probably effected by insects which are attracted by the scent of the flowers.

Anamirta cocculus is very closely related to Arcangelisia flava (L.) Merr. with which it is sometimes confused. However, they can easily be distinguished. The domatia in the leaves of Anamirta cocculus are hairy patches while in Arcangelisia flava they are hollow with the margin of the aperture hairy. Besides, Anamirta cocculus has white wood while Arcangelisia flava has yellow wood.

Anamirta cocculus occurs naturally in forest and forest fringes, in thickets, on river banks, near streams, in savanna, up to 400 m altitude, on volcanic basalt, limestone, calcareous rocks and sandy soils. It prefers a seasonal climate.

Propagation of Anamirta cocculus by seed seems the most appropriate means for any future plantings.

Fruits, stem or roots of Anamirta cocculus are collected from the wild when required.

When used as a medicine the ripe fruits of Anamirta cocculus are in general simply dried. For its use as a fish poison the same procedure can be followed or the fruits may be employed fresh.

In view of its large geographical distribution and its occurrence in a wide range of habitats it is unlikely that Anamirta cocculus is seriously threatened by genetic erosion. Despite its longstanding use no reports of cultivation, let alone breeding efforts have been recorded.

Picrotoxin and picrotoxinin are substances with a distinct pharmacological profile, i.e. GABA antagonistic activity by interacting with the barbiturate binding site on the receptor. Due to this mechanism the compounds can, and have been used as antidotes in barbiturate poisonings. Due to their extremely narrow safety limits and variable outcome, however, they will never be used in general medical practice. On the other hand, in medicinal research, picrotoxinin is generally used as an experimental substance in the laboratory, and in laboratory animals. Therefore, Anamirta cocculus will most probably stay of local importance.

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N. Wulijarni-Soetjipto & J.L.C.H. van Valkenburg

Wulijarni-Soetjipto, N. & van Valkenburg, J.L.C.H., 2001. Anamirta cocculus (L.) Wight & Arn.. 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