The Apocynaceae in Materia Medica.

By George M. Beringer.

(Continued from Vol. 66, page 550).

Strophanthus kombé.

Strophanthus Kombé Oliv., confounded from the first with S. hispidus. The species was created by Oliver from the specimens sent by Dr. Kirk from Zanzibar and those collected by the expedition of Livingstone. The differences which separate this species from S. hispidus are, on the whole, small and gradually effaced by the existence of a series of stages in the transit, in such a way that we may admit with Blondel, and with Oliver likewise, that the Kombé is only an oriental form of the hispidus, possibly a variety. The form Kombé commences to appear in the region of the great lakes, then extends as far as the eastern coast. Among other botanical characters are the form and the less length of the calyx lobes in comparison with the tube of the corolla, the consistence of the calyx and bracts, the scarcity of inflorescence, the pubescence more abundant on the leaves, the size of the fruit, the caducity of the bracts, the considerably much larger seed, the abundance and length of hairs on its surface, the increased length of the awn and of the shaft, the color of the seed more or less green, the great length of the funiculus, the elongated form and the number of the lenticels on the fruit, etc., etc. All these characters which seem clear at first sight, become indefinite when we examine a sufficient number of specimens, permitting the verification of the intermediary stages.

The S. Kombé inhabits the basin of the Zambesi and the Shire where it serves as the arrow poison. Indicated as about the Victoria Falls, an equal distance from the two oceans, it extends to near the eastern coast (Mozambique), and to the north in the region of the great lakes of the centre.

The plant is analogous with the S. hispidus. It flowers in October and November. The various parts, wood, bark, etc., are strongly bitter. The rough pubescence is very marked upon the leaves, the inflorescences and even the flowers. A specimen of the fruit sent by Dr. Kirk measured 32 centimetres in length. The upper extremity tapering at great length, but broken. It is said to be terminated by a stigmatic disk, greatly developed. External surface strongly wrinkled longitudinally, color a dark brown, lenticels extremely numerous, transversely elongated and irregular, forming a striation, close, and light brown. The commercial fruit is more or less scraped; bearing at times the remains of the fibres of the mesocarp, appearing as longitudinal striations. More frequently the endocarp alone remains, straight or curved, always fragile and frequently broken, the color yellowish or clear fawn, or a little reddish, often marked by regions more deeply brown, longitudinal and badly limited. The lower extremity is notched, the upper extremity always broken. The internal face is shining, color a little green. It is about 25-35 centimetres in length and 2 centimetres in diameter.

The structure of the pericarp is a little different from that of S. hispidus and that of S. niger; the parenchyma cells here are sinuous, flattened, or in some regions more open. The sclerotic fibres are nearly constantly associated with a ligneous bundle. The longitudinal fibres are flattened quite regularly.

The seeds are striking at once by their color, generally light, their surface strongly tomentose, their silky changeable lustre. The seeds isolated, as they ordinarily arrive in commerce, are in form lanceolate, at times rounded at the base, at other times much more slender even in the same specimen. The dimensions are 11-22 millimetres in length, 2 ½- 5 millimetres in breadth, and 1-2 millimetres thick. The margin is often sinuate, one face quite plane or even concave. The surface is covered with hairs much longer, much closer, more woolly than in the S. hispidus, and quite visible to the naked eye. They vary in color from cream white to nearly a brown, with all the intermediary colors and sometimes even with a little different tint upon the two faces of the seed. But the color ordinarily is a greenish gray or a greenish yellow. From handling the hairs drop off and the color then becomes a little more deep. The raphe is ordinarily well marked, very prominent on one side, and quite long. The fracture is white or grayish; the odor is specially well marked, but only if we scrape the seed; the taste is atrociously bitter.

The awn which surmounts the seed is very handsome; the color a little grayish in mass, and is borne upon a very long shaft of which the naked part is always much longer than the plumed part, but not three or four times as long, as some one has said. The naked part generally 4-5 centimetres and the plume 3-4 centimetres. The hairs are whitish, silky, brilliant, often 5 ½- 6 centimetres or more long, always easily broken. They spread quite well without becoming entirely horizontal. The naked part of the shaft is more resistant than that of the hispidus. It is sinuous and of a pale yellow color. The albumen and the embryo are very similar to those of hispidus. The radicle is quite long and the cotyledons very thick. The hairs retain so much air that the seed floats a long time in water.

We may distinguish three varieties based upon the anatomical structure, and in these may exist yet others. The first variety is the largest and possesses a longitudinal projection on the ventral face, quite sharp, with the thin borders folded and the dorsal face quite convex, turned over at times like a tuft of moss.

The second variety is more attenuated towards the base, the point, ordinarily asymmetrical, shows an abrupt depression upon the dorsal face; the hairs are longer and changeable.

The third variety is less lanceolate, more sharply attenuated at both extremities; the ventral face much less flat; the tufted part a slender filament that becomes spread about the middle of the ventral face. It seems that the anatomy differentiates these forms not yet referable to definite species. In the external layer the thickenings are quite varied in the forms. The second tegumentary layer with the flattened cells more or less dilated between the depressions of the tegmen; in the albumen, the cell walls vary in thickness and aspect. In none of these are crystals of calcium oxalate. The action of sulphuric acid is the more remarkable upon this seed so rich in Strophanthine: scarcely is the section placed in the reaction than an intense green coloration is revealed in the entire thickness of the albumen; then rapidly likewise, but less, about the tip and its immediate neighborhood; the coloration shows in the embryo, occasionally, with a bluish tint; the color is always less bright than in the albumen. Shortly the aspect changes: the albumen becomes greenish yellow, while the embryo passes to an intense blue. Finally, it gradually assumes a reddish or even greenish tint with here and there a few red streaks.

Strophanthus paroissei.

S. Paroissei Franch. an African species, inhabiting French Guinea to south of the Senegal. The plant is but little known, bears the indigenous name of Bini-bande, and presents branches covered with lenticels and relatively small leaves. The follicle seems quite characteristic, very shrunken and obtuse, rounded about the summit, 18-20 centimetres in length. The naked part of the awn or shaft is nearly 3 ½ centimetres, Franchet says 4-5 centimetres. The plumed part always quite small, 18-20 millimetres. The hairs of the awn are quite long, nearly 3 centimetres, white, slightly yellowish, fine, brilliant and silky.

The seed is lanceolate, the form occasionally somewhat asymmetric, 10-15 millimetres in length, 3-3 ½ millimetres in breadth, and 1 ½ millimetres in thickness. The posterior extremity is rounded, the anterior lengthily attenuated into a very fragile shaft. The surface chocolate brown, covered with short, crowded brown hairs easily seen with a lens or even with the naked eye. The ventral line is rarely very clear.

This species is important because it inhabits the same regions as the S. hispidus and S. minor and the seeds closely resemble those, so that the substitution or admixture becomes very certain. The bitterness of this seed is relatively weak.

The first layer of the seminal tegument shows cells with the lateral thickenings quite small, convex, but not at all hemispherical. The second tegument is composed of cells extremely crowded and compressed, is a deep brown and is very little thickened. On a level with the raphe the second tegument divides into two, the external zone being very dark, the internal much more clear; between these is placed the fascicles.

With sulphuric acid the section is colored at once a yellow with a little greenish (but it is the droplets of oil which becomes colored), then to a rose (tissue of the cotyledons). But the color is never a decided green. This character, in conjunction with the abundance of the macles of calcium oxalate in the embryo and with the taste but slightly bitter, seems to indicate that the seed is quite poor in active principle.

The woolly Strophanthus of Zambesi.

Strophanthus asper Oliv.—Although the botanical information is reduced to a minimum, it is evident from a single inspection of the seed that one is dealing with a distinct species. But, after more than six years, the primitive name given by Blondel, "Strophanthus lanieux du Zambèze," remains a résumé of our geographic and botanic knowledge upon this subject.

The awn is greatly developed toward the summit, garnished with hair, relatively short, directed obliquely from base to the summit and a little yellowish. The naked region of the shaft is very short.

Regarding the seed itself, it is at once remarkable for its yellowish-white color, shining, owing to the tomentum, extremely thick and long, with a soft woolly fleece. These hairs are directed from the base toward the summit; detached they form in the drug frequently handled small woolly balls. Their length exceeds 3 or 3 ½ mm. especially upon the margin of the seed.

Under these hairs the color of the seminal tegument is a bright maroon. The form is vaguely lanceolate, rather oblong, sometimes a little irregular, the larger proportionally quite variable; rounded in the rear and a little tapering in front. The anterior portion covered by the hairs frequently difficult to be seen. The ventral face, a little flattened, presenting a small brownish tuft, a little inflated at its termination, towards the middle of the seed. The surface is longitudinally striated. The dimensions are 10 to 20 mm. in length (ordinarily 14 to 16), 3 to 4 mm. in breadth and 1 ½ to 2 mm. in thickness.

Macerated in water the seeds alter rapidly, soon exhaling a very disagreeable odor. The albumen is grayish-white, less horny, less cartilaginous than in the other species. The embryo is dull white with thick cotyledons and a radicle infinitely shorter than in the S. hispidus or the S. Kombé.

The transverse section shows that in the external layer the lateral cell thickenings are very little convex, and gives to the section the aspect of a lenticular fusiform body by coalescence with the corresponding thickening of the neighboring cell. The second layer of the tegument is formed of cells much flattened and nearly indistinct. The cells of the albumen and the thick embryo are relatively small.

With concentrated sulphuric acid, the cotyledons give gradually a bright rose coloration, commencing about the vascular bundles. The color is much less intense in the albumen. In a few sections the red color is preceded by a yellow coloration. After one hour the albumen becomes red and the embryo violet.

The glabrous Strophanthus of Gaboon.

Strophanthus Sp.? Important as have been the numerous expeditions of M. Vincent, Dr. Bellay, etc., and the physiological studies by Polaillon and Carville and the chemical investigations by Gallois and Hardy, Catillon, Arnaud, etc., these seeds can not yet be referred with certainty to any species botanically determined. According to M. Franchet, it is a fact, however, remarkably interesting: that in all the Strophanthus with glabrous seeds (all the Asiatic species are in this class), there exists a constant relation between the absence of all villosity and the length of the point that terminates the anther. Now among the numerous African Strophanthus, two only present this character of the anthers, the S. gratus Franch. and S. Tholloni Franch. which inhabit precisely the region of the origin of S. glaber. According to Thollon this second species bears at Gaboon the name of Onaie. It is thus allowable, with Franchet, to attribute this seed to one or the other of these plants, provisionally and the rather to S. gratus which is likewise from the Gaboon, while the S. Tholloni is from the regions of the rapids of the Ogoway consequently more to the East.

The S. gratus Franch. (Roupellia grata Wall et Hook., Nerium guineense Brongn., etc.) is a small tree, according to Griffon du Bellay, but more probably a liane. The plant inhabits Guinea, the Gaboon and Sierra Leone, whence it was introduced into culture by Whitfield under the name S. Stanleyanus.

The S. Tholloni Franch. is probably the species of which the fruits were sent by Thollon containing seeds very analogous to those of the S. glaber. It is a long liane of western Africa inhabiting the French region of the Congo, especially the course of the upper Ogoway and the Cameroon, and its extent may be quite far towards the centre of the continent. The lobes of the corolla are short and sharp in the S. Tholloni and nearly round in S. gratus.

The S. glaber serves for the fabrication of the arrow poison in this district. [The bark and leaves are poisonous, but less so than the seeds. To obtain one kilogramme of the seed 150 pods must be collected.
It is this seed which is employed for the kombé poison. The seeds deprived of their awn, are beaten between two stones, and the paste worked up with a knife into a creamy consistence by the addition of a little water or certain vegetable juices, and becomes a red color from exposure to air. This paste is applied to the points of the arrows or they are rolled in the substance, to which is previously added some adhesive ingredient (the mucilaginous bark of a Tiliaceae, the latex of a Euphorbium rich in caoutchouc, the juice of the petiole and leaves of two indigenous plants not determined, etc.). The substance dried, the arrow is ready. The effects are very rapid, and the game wounded falls within the limit of one hundred metres. The hunter hastens then, to excise with a knife, all around the wound, or better, forces in the wound the juice from a branch of Adansonia digitata. These precautions taken, the game maybe eaten with impunity. The act of poisoning their neighbor flourishes among the Gaboonese with all its splendor, and the Inee takes the first rank among those numerous powders, the recipes of which these savages religiously transmit as an inheritance.]
For a long time the seeds were confounded with those of S. hispidus, from which they may be easily distinguished.

Each follicle is 30 to 35 cm. in length, strongly ligneous and very thick. The exterior surface is brown or reddish, with oval lenticels. In its commercial form, it is bound with the leaf of a palm. The endocarp is fusiform, swollen about the middle 3 to 4 cm. in diameter. The color externally is yellowish to brownish yellow. The surface is quite smooth, dull, non-striated. The interior surface is fawn colored, uniform, shiny, with a brilliant silkiness.

The seeds are much shorter than the other species studied. The shape of the isolated seed is lanceolate with the base ordinarily rounded or truncated and the summit lengthily attenuated with the margins more or less sharp, especially at the base, oftentime somewhat undulated, always somewhat flattened, never cylindrical, the seeds relatively large averaging 13 to 16 mm. in length by 3 to 4 ½ mm. in breadth and 1 to 1 ½ mm. in thickness. The dorsal face clearly convex, the ventral flat or even concave. A small keel exists at times near the shaft upon the dorsal face. The surface of this grain is absolutely glabrous and presents only the longitudinal plaitings. The color is an ochre-yellow, fawn, or cinnamon, but often deeper or greyish. The appearance is waxy, dull, tarnished; the fracture is horny, whitish or gray; the odor is especially well marked; the taste extremely bitter. It requires about 35 seeds to weigh 1 gm. The naked part of the shaft is very short (about 1 cm.) in comparison with the plume, which often attains 4 cm. The hairs of the same are sometimes nearly 7 cm. in length; they are numerous, silky, brilliant, fine, fragile, white, viewed in mass yellowish or grayish and diverging, describing a graceful curve.

The envelope is relatively very thin; the albumen thick, cartilaginous, transparent; the embryo is not thick, the radicle is long as in the hispidus and Kombé.

On transverse section the seed shows first the external layer of the tegument with the thickened cells large and short, a little larger toward the internal region. The second seminal zone is strongly compressed especially on the inside and the first layer of the albumen is strongly thickened on the outside. The cells of the embryo are often not distinct in outline; they are rich in oil.

With concentrated sulphuric acid the coloration is effected slowly and is never green. At first yellow, then becomes a bright rose. The rose appearing in the neighborhood of the vascular fascicles, and remaining more deeply so there. Finally, very slowly, a violet color is produced.

Strophanthus divaricatus.

S. divaricatus Hook, et Am., Pergularia divaricata Lour.; S. divergens Grah.; S. dichotomus β Chinensis Ker. This species occupies the sea coast of China. The carpels are strongly divergent and make with each other an obtuse angle. The follicle is relatively small, 13-14 cm. in length and nearly 4 cm. in diameter; the fruit is quite slender and the base strongly notched about the insertion of the peduncle. Externally it is blackish brown, strongly striated longitudinally, and here and there a little yellowish or reddish in places. The interior is smooth, greenish yellow and generally dull. The seed is 15-17 mm. in length by 3-3 ½ mm. in diameter and 1-1 ½ in thickness, with margins a little undulate. Color a blackish grey to deep brown. The ventral face bears a longitudinal line, brighter in color, and running nearly the entire length. The naked part of the shaft or awn is very short, 4-6 mm., the plume is much longer, 2-3 cm., and brighter in color.

The hairs of the awn are white, in mass grayish, quite long, 3 ½ to 4 cm., and relatively less fragile and more rigid than in the other strophanthus. They are directed forward here horizontally, then little by little they return to the rear, passing even beyond the body of the seed. The attitude is inverse to those of the S. Kombé. The taste is much less bitter than that of S. glaber. With concentrated sulphuric acid the albumen and the embryo give a red, orange coloration.

Strophanthus Caudatus, Kurz., S. dichotomus. A.—P. DC. This species occurs in Java, India, Tonquin, Singapore, the Malay peninsula, and is cultivated at Reunion.

The variety, Marckii, inhabits India and Malacca, and, according to Franchet.the seed greatly resembles that of S. glaber of Gaboon. It is feebly bitter.

Falsifications.—The substitution of one sort for another is frequent, as well as the admixture of the various products of different species. The admixture of seeds, which had been previously extracted with alcohol, is likewise a fraud, to which attention is directed. The frightfully bitter taste of strophanthus is somewhat reduced by this treatment, and an excellent character for its detection is the appearance of the seed which becomes dull, and of a greenish-brown color, with the hairs agglutinated by the resin which is dissolved by the alcohol. The distinction between the seeds foreign to the genus, is quite easy, a glance of the eye ordinarily suffices. The single falsification of this nature which is really serious, is the substitution of a seed, at first attributed to a Wrightia, or to Holarrhena antidysenterica, but which E. M. Holmes has proven to be derived from Kickxia africana, Benth. This seed is a uniform chocolate-brown color, attenuated at both extremities, inflated spindle-like about the middle, and twisted in an S, and bears on one face a depressed line. The surface examined with a lens, appears longitudinally striated. Dimensions, 9 to 16 mm. long, 2 to 2.5 broad at the middle, and 1.5 to 1.8 thick. The fracture is clear and horny, brownish-white; the odor resembles that of the strophanthus, and the taste is extremely bitter.

The seeds are provided with awns [According to E. M. Holmes, this seed is destitute of an awn, the tuft appearing like a plumose awn, being really the hairy funiculus or stalk, by which the seed is attached to the pod.—G. M. B. ], directed backward in the fruit. These awns are formed of a straight and rigid axis, in the neighborhood of 1 cm. long, cylindrical, and slender, the silky hairs which it bears, attain 5 cm. in length, and are very delicate, and brilliant; in color, white, slightly yellow.

A transverse-section shows the cotyledons broad and thin, sinuous, and folded upon themselves, very different from those of the strophanthus. The external layer is formed ot irregular, large, brown cells, often badly limited, but without the characteristic circular thickenings. The cellular walls of the albumen are very thick, and the cells of the embryo contain numerous macles of calcium oxalate.

The section treated with sulphuric acid gives a yellow coloration in the embryo, which then changes to an orange and then a red wine lees color, which persists for a long time. The liquid likewise becoming strongly colored.

Chemical Constituents of Strophanthus.—In 1865, Pelikan and Vulpian made the first physiological study of strophanthus with a hydro-alcoholic extract of seeds brought from Africa by Griffon du Bellay. In 1869, Fraser published his first work giving the chemistry and therapeutics. He studied in reality, not the S. hispidus, but the S. Kombé, and applied the name strophanthin to a principle which he isolated imperfectly and which he supposed to be an alkaloid. Then Legros made a series of experiments with the poisoned arrows of the Pahouins. In 1872, came the experiments of Palaillon and Carville, who employed the S. glaber likewise under the name of S. hispidus. In 1877, Gallois and Hardy in their analyses obtained results different from those of Fraser, which now is fully explained, as instead of the S. Kombé employed by Fraser, they used S. glaber. They isolated two substances: the one Inéine extracted from the awns, a body with alkaloidal properties and peculiar physiological action, but of which the existence even was afterwards contested by Elborne and by Gerrard; the other, the strophanthin crystallizable, separated from the seeds alone, and which according to these authors was neither an alkaloid nor a glucoside. Catillon in numerous analyses of the products of various origin obtained different strophanthins, some amorphous, others variously crystallized. Fraser, Adrian and Bardet, Catillon etc., showed the glucosidal nature of the principle and admitted the co-existence in the strophanthus of another body, alkaloid according to some, glucoside likewise according to the others. Finally, the magnificent work of Arnaud proved the absence of strophanthin, properly named, in the S. hispidus, its presence in S. Kombé, the replacement of the strophanthin by ouabain in the S. glaber. He gives the composition of these bodies, and indicates the formulas, and shows finally the relation between these two important substances, of which the one (strophanthin) is a higher homologue of the other (ouabain).

The strophanthin from S. Kombé is a non-nitrogenized glucoside with all the characters of the glucosides and readily yields with dilute acids glucose and strongly toxic substance, strophanthidin, of which the effects are not otherwise the same as those of strophanthine.

It crystallizes readily and is neither a glucoside nor an alkaloid. Strophanthine exists in S. Kombé in the proportion of 0.4 to 0.9 per cent., while ouabain is furnished by S. Glaber to the extent of 4.5 to 5 per cent.

Strophanthin is accompanied in the seed by another glucoside and by a large proportion of a deep green fixed oil (according to Catillon 32 per cent). Fraser has also separated an acid for which he proposed the name of kombic acid. In addition there is contained a resin, mucilage and an albumenoid substance.

Physiological and Therapeutical Action.—It was not till about 1885, that physicians following Fraser's experiments commenced to employ strophanthus. For a long time the results were contradictory and confusing. The same cause of errors which were fallen into in the chemical studies, appear here, the mixing of seeds, improperly named or falsified, occasioned differences, and the results were not comparable. On the whole, strophanthus is a muscular poison, acting upon all the striated muscles but more especially upon the heart. The action upon the heart can be obtained with the exclusion of all other action and with neither accumulation nor gastro-intestinal troubles. It seems established that strophanthin is not diuretic, nevertheless strophanthus is distinctly so. In physiological dose strophanthus augments the force and the amplitude, diminishes and regulates the number of the pulsations. By a toxic dose the paralysis of the heart is accompanied by dyspnoea, nausea, vomiting, weakness and muscular resolution. It is certain that its direct action is rapid and that it is well tolerated.

In answer to the query which strophanthus should be employed? the author favors the adoption of the Strophanthus Kombé for pharmaceutical uses for the reasons that it is most frequent in commerce, is very active and quite easily recognized.

Anderjow seeds.

The seed properly known under this name is that of the Holarrhena antidysenterica. Conessi bark is a product from the same tree. Both of these drugs have been admixed with, or entirely substituted by, inert products obtained from Wrightia tinctoria, or other species of Wrightia. The products of Alstonia scholaris have likewise been confused with these drugs. These substitutions explain the failures that have been obtained in Europe with drugs so universally employed in India.

In the appendix to the Pharmacopoeia of India, by Waring, Wight has established the distinctive characters of these three trees in which the size is the same, the barks latex bearing and scaling off in strips; the flowers are white, and the inflorescences identical, the follicles long and slender and united in twos, the seeds garnished by tufts of white hairs. In Holarrhena and in Wrightia the leaves are opposite, oval, rounded at the base and attenuated at the apex, while in the Alstonia the leaves are verticillate, attenuated at the base and rounded at the summit. In Holarrhena the tube of the corolla is two or three times longer than the calyx, twisted to the left in aestivation, with naked throat, without appendages, stamens included and inserted in the dilated part of the tube. In the Wrightia tinctoria the tube is relatively shorter, prefloration twisted to the right, the sagittate stamens exserted, forming a cone about the stigma, and a crown of filamentous glands laciniate, velvety. The disposition of the hairs borne by the seed is likewise quite characteristic; in the Holarrhena the tuft of delicate silky white hairs is borne at the upper extremity of the seed; in the Wrightia it is the lower extremity, and in Alstonia both extremities are ornamented.

Holarrhena antidysenterica, Rob. Br. (Nerium antidysenterica, L. (in part). Echites antidysenterica, Roxb. Chonemorpha antidysenterica, G. Don. Holarrhena pubescens, Wall. H. Codaga, G. Don. H. malaccensis, Wight). This is a shrub, or at most a small tree, of which certain forms are glabrous and others tomentose, abundant in the mountains and dry forest regions of India. It is known in the various regions under a multitude of vernacular names. [Karra, Kora, Keor, Kuar, Kari, Dhudi, Kogar, La-thou, Indeijaw, Dudhuki-Lakri, Kureya, Kaureya (Hindj, Vepali, Veppaula, Veppalay, Kulappalaivirai; Kodoga-pala, Pala-chettu, Giri-mallika, Kalingamus, Kodisa-palachettu, Kodisa-pala, Kola-mukki-chakka, Kutajamu, Pedda-ankudu-chettu. Palavarenu, Ankudu, Palla-coodija, Mauoopala, Girimallika, Inderjo, Dowlakoora, Koora, Pomdhra-koora, Dood-kora, Conapola, Koorchi, Curayja, Inderjauschiren, Palla-patta, Kiam, Kachri, Dudkuri, Tiwajs, Lissan-el-asafeer, Caraja, Cutaja, Amkudu-vittum, Dadhi-Ruar, Ankria, Kachii.]

[To be Continued.]

The American Journal of Pharmacy, Vol. 67, 1895, was edited by Henry Trimble.