Source, Etc

The purple foxglove, Digitalis purpurea, Linne (N.O. Scrophularineœ), is a handsome biennial herb, widely distributed throughout Europe and common in England, where it occurs wild and is also cultivated as a garden plant, as well as for medicinal use. Much of the commercial drug was formerly imported from Germany, but latterly (1915-1918) large quantities have been collected and dried in this country. It appears to have been long used as a domestic medicine; it was introduced into the London Pharmacopoeia as long ago as 1650, although it did not come into frequent use until about a century later. .

The foxglove produces, like henbane, in the first year a rosette of leaves, but no aerial stem; in the second year a tall, erect, usually simple stem that may attain a height of 2 metres or more, and bear numerous flowers. The latter are well characterised by their crimson bell-shaped corolla, with darker spots on the inner part of the mouth; the ovary is conical and contains two cells with numerous ovules; the stamens are didynamous.

The plant flowers during the summer months, and the leaves for official use are directed to be gathered from plants commencing to flower, when the presence of the flowers precludes any possibility of the leaves of other plants being collected by mistake. They should be completely dried immediately after collection and preserved quite dry in air-tight containers, when they will retain their activity unimpaired; air-dry leaves are said to deteriorate rapidly but on this point the evidence is conflicting.

Description

Foxglove leaves vary usually from 10 to 30 cm. in length, but may attain as much as 15 cm. in breadth; in shape they vary from broadly ovate to lanceolate, those on the upper part of the stem being the narrower. Towards the base of the leaf the lamina is contracted and passes into a winged petiole of varying length, down which the lower lateral veins are usually decurrent, the petioles of the lower leaves being longer than those of the upper. The upper surface is dull green in colour and bears numerous short hairs, the under surface paler and more or less densely pubescent, the hairs being seen under the lens to be simple and unbranched. The midrib is prominent on the under surface; the majority of the lateral veins leave the midrib at a rather acute angle (especially in the narrower leaves) and gradually curve round towards the apex, passing into smaller ramifications near the margin. The latter is crenate or irregularly crenate-dentate, the apex blunt or subacute. Each crenation terminates in a small cartilaginous point which is brown or black in old leaves but colourless in young; a veinlet enters each crenation and spreads like a brush, a marginal veinlet approaching from either side, the whole forming a well-marked character of the foxglove leaf. The odour of the fresh leaves is unpleasant, and the taste of both fresh and dried leaves disagreeably bitter.

Although the leaves are directed to be collected from flowering plants, it is not possible to distinguish these accurately from those of the first year; generally speaking, the latter are narrower and have longer petioles, whilst the biennial leaves are usually broader and have shorter petioles. The separation is, however, not material, as the first and second year's leaves are about equal in activity.

Microscopical Characters

Under epidermis composed of cells with wavy walls and smooth cuticle; stomata numerous and small; hairs abundant and of two kinds, either simple, uniserial, three to five or more cells, thin-walled, often warty, and frequently collapsed; or small, stalked and glandular. Midrib normal in structure and free from bast or pericylic fibres. No crystals of calcium oxalate in any part of the leaf.

The student should direct his attention particularly to

(a) The crenate margin,

(b) The winged petiole with decurrent veins,

Fig. 35.   Foxglove leaf. Under surface, showing the lower veins decurrent in the petiole. About two thirds natural size.

Fig. 35. - Foxglove leaf. Under surface, showing the lower veins decurrent in the petiole. About two-thirds natural size.

(c) The simple unbranched hairs,

(d) The course taken by the lateral veins; and should compare these leaves with

(i) Matico leaves, in which the veinlets are depressed on the upper surface, dividing it into small squares, (ii) The possible substitutions mentioned below.

Constituents

Although the constituents of foxglove have repeatedly been the subject of research, our knowledge of them remains incomplete. The activity of the leaves appears to be due chiefly to digitoxin, digitalein (gitalin, Kraft) and digitophyllin; other constituents are saponins, digitoflavone (luteolin), an irritant resin (digitalic acid), and a very active oxydase.

Digitoxin, C34H54O11, is a well-defined, colourless, odourless, crystalline, bitter substance, insoluble in water, but nevertheless passing into solution in appreciable quantity when foxglove leaves are infused in that menstruum. It is the most toxic of the active constituents of the leaves, and is cumulative in action, being apparently fixed by the muscles of the heart. It is hydrolysed by dilute mineral acids yielding digitoxigenin, C22H3204, and a sugar, digitoxose, C6H1204. It may be identified by Keller's reaction, which consists in dissolving it in glacial acetic acid, adding a drop of ferric chloride solution, and then gently a stratum of sulphuric acid; the upper part of the latter is coloured red, whilst above this an indigo blue band gradually appears.

Dry foxgloves leaves contain from 02 to 0.3 per cent, of digitoxin, the first year's leaves containing as much as the second. Wild plants contain more than cultivated, but the quantity rapidly diminishes towards the end of the flowering stage.

Digitalein (0.3 to 0.9 per cent.), a purified form of which is known as gitalin, is an amorphous, in hydrated form crystalline, glucoside soluble in water; it has a marked action on the heart and as it is not cumulative it is believed to be more valuable therapeutically than digitoxin. It passes readily into the infusion. By heating it changes into anhydrogitalin and by hydrolysis it yields anhydrogitaligenin and digitoxose.

Digitophyllin, crystallising in plates melting at 232°, is probably methyl-digitoxin and gives the same colour reaction as digitoxin.

Digitoflavone, (luteolin) is a yellow colouring matter allied to quercetin.

The saponins appear to comprise digitsaponin, amorphous, soluble in water and gitin, crystalline and insoluble in water. The digitsaponin accelerates the heart-beat but is non-cumulative.

The active constituents of foxglove seeds are:

Digitoxin (see above).

Digitalin, a crystalline, water-soluble, active glucoside not identical with digitalein.

Digitonin, a crystalline saponin resembling gitin but not identical with it.

The digitalins of commerce appear to be variable mixtures:

Homolle's digitalin is amorphous and a mixture of digitoxin and digitalin.

Nativelle's digitalin is crystalline and chiefly digitoxin.

German digitalin is amorphous and said to consist chiefly of digitalein.

Digitalinum verum is amorphous and said to be the best variety of digitalin for medicinal use.

Several other species of Digitalis have been examined; all were found to be toxic.

Uses

Foxglove increases the activity of muscular tissue, especially that of the heart and arterioles, and is employed in most forms of cardiac failure. Digitoxin is cumulative, and the action of preparations of foxglove must therefore be watched.

Assay

Since the therapeutical activity of foxglove leaves is due to more than one glucoside, it is obviously impossible to assay the leaves by determining one only of these, e.g. digitoxin. No method of determining digitalein or digitalin is known. Hence chemical methods of assay fail, and recourse must be had to the physiological assay (compare p. 168).

Adulterations

Leaves of D. Thapsi, Linne, imported from Spain; greyish green or yellowish green, lamina less decurrent, hairs very numerous, long, curling. Said to be more toxic than D. purpurea.

Mullein leaves {Verbascum Thapsus, Linne); woolly; hairs branched.

Comfrey leaves (Symphytum officinale, Linne); lanceolate or ovate; isolated stiff hairs.

Primrose leaves (Primula vulgaris, Hudson); nearly spathulate; lateral veins straight, dividing near the margin.

Ploughman's spikenard {Inula Conyza, de Candolle); margin either entire or dentate, with horny points to the teeth.

Elecampane leaves {Inula Helenium, Linne); lower lateral veins not decurrent.