Fern

FERN (Filix), an herbaceous, spore-bearing plant of various species of the polypody family (Polypodiaceae), of the fern class (Filicales). The main representative of the family is the male (from the Greek mas), or black fern, Dryopteris Filix-mas Schott [synonyms: Aspidium Filix-mas Schwartz (F. VII), Nephrodium F.-m. Richaux, Polystichum F.-m. Roth]. It is very widespread in Europe, America down to Peru, Northern Asia, Sakhalin, Japan, Java, and other places. The large, pinnate, green leaves of the plant, sitting on short petioles, form a tuft; the leaves and stem are covered with hair-like scales, the pinnae of the leaves are short-petioled and lanceolate; the underside of the leaves is dotted with two-rowed clusters of sporangia (sori) covered with indusia; the sporangia are repositories for spores; the spores are dark brown, of irregular ribbed shape. For medical purposes, the upper part of the rhizome together with the bases of the leaf petioles is used as an anthelmintic remedy. The rhizome (Rhizoma Filicis maris) is gathered from wild-growing plants in autumn; it is freed from scales, roots, and dead parts and dried. It is flat at the base, 10–30 cm long, 1–2 cm thick; it terminates in an apical bud and is covered on all sides by imbricately arranged bases of leaf petioles; the rhizome is dark brown on the outside, light green or yellowish-green on the inside; the fracture is even, and on cross-section it is irregularly polygonal; the odor of the rhizome is peculiar, unpleasant, and when the section is moistened with a solution of sodium hydroxide, it smells of violets; the taste is initially sweetish-astringent, then slightly scratchy and acidic. The rhizome consists of a slit-like ground tissue with cells containing starch and tannin; in the intercellular spaces there are pear-shaped or flat glands; they secrete a green-yellow secretion containing the active principles. Rhizomes that are brown or yellow on the inside are unfit for use; the loss of the active properties of the preparation is judged by the disappearance of the green coloration in the rhizome (especially during prolonged storage of the rhizome); for medical purposes, it is recommended to use rhizomes stored for no more than one year. The rhizomes are kept in closed dark glass vessels. Adulterations and falsifications. Pharmacies frequently receive rhizomes and preparations made from other species of ferns; the latter differ from the male fern in appearance, rhizome shape, the size of starch grains, and the potency of the preparations. The main active substances of the fern are extracted from the rhizome with ether together with green oil (see below). The richest in active substance content is the male fern gathered in September in mountainous places, on shale and volcanic soil. The isolation of the main substances of the fern and the study of their physicochemical properties is the credit of Boehm, Poulson, and Kraft (Boehm, Poulson, Kraft). 1) The main active principle is filmaron, or aspidinophilicin, C₄₇H₅₄O₁₆ (Kraft) (up to 0.5%), a straw-yellow powder melting at 60°; easily soluble in acetone, ether, acetic ether, strong acetic acid, etc.; sparingly soluble in petroleum ether, alcohol, insoluble in water; soluble in alkalis with decomposition; in general, it is unstable and easily breaks down into aspidinol and filicic acid (Kraft); both have been given detailed structural formulas, but these have not yet been definitively established. 2) The second active substance is considered to be filicin or filicic acid (fern acid); it is isolated from the ethereal extract in crystalline form, devoid of anthelmintic properties. The chemical formula of crystalline filicin is C₃₅H₃₈O₁₂ (Boehm); melting point 184–185°; readily soluble in chloroform and fatty oils; fern acid can also be in an amorphous form (C₃₅H₄₂O₁₃ according to Poulson); it is obtained by acid precipitation of a salt solution of the crystalline form (C₃₅H₄₀O₁₂ according to Poulson); the amorphous acid, in contrast to the crystalline one, is active, but easily converts into the crystalline inactive form; this explains the loss of potency of the rhizome upon its long-term storage. 3) Flavaspidic acid, C₂₃H₂₈O₈ (according to Boehm), is also found in the rhizome of the female fern Aspidium Filix-femina and the narrow-dilated fern (Aspidium spinulosum); yellow tablets or prisms. 4) Albaspidin, C₂₅H₃₂O₈; thin, colorless, needle-like crystals, easily soluble in ether; obtained from fern acid by boiling it with alcohol. 5) Aspidinol, C₁₂H₁₆O₄; pharmacologically poorly active; thin yellowish-white crystals, soluble in ether and chloroform. 6) Floraspin (flavaspidin), C₂₃H₂₈O₈; light yellow, needle-like crystals, soluble in chloroform and acetone. 7) Aspidin, C₂₅H₃₂O₈; yellow crystals with the properties of fern acid; according to Hausmann, it is found only in Aspidium spinulosum. 8) Aspidinin, alkali-soluble colorless crystals. All the indicated active principles of the male fern are, according to Boehm, methylated derivatives of phloroglucinol. The methylated derivative of phloroglucinol (according to Boehm) or filicinic acid is pharmacologically inactive; upon the replacement of hydrogen in it by butyric acid (C₄H₇O₂), the first active product is obtained—butyrylfilicinic acid; all the main fern substances are combinations of two, three, or more butanones; thus, for example, albaspidin and flavaspidic acid are a combination of two butanones; fern acid of three, filmaron of four. In other species of ferns, active principles have been found that are identical in chemical and pharmacological properties with the substances of the male fern; for example, from Aspidium (Polystichum) spinulosum, Poulson isolated yellow (analogue of aspidin) and white polystichic acid (analogue of albaspidin). In addition to the active substances named above, a number of other products have been discovered in the male fern, many of which are inactive. Of these: 9) Filicinic acid, C₈H₁₀O₃, a cleavage product of fern acid, flavaspidic acid, and aspidin. 10) Filixnigrins, amorphous, dark brown substances formed upon the destruction of other principles during the processing of the rhizome. 11) Filix-tannic acid (C₈₂H₇₆N₂O₃₈ or C₄₁H₄₄N₂O₂₂ + 2H₂O), a glycoside; under the influence of air and light, it oxidizes and breaks down into sugary and coloring substances (phlobaphene and filix-red, C₂₆H₁₈O₁₂); the latter causes the brown coloration of the parenchyma of the old rhizome; according to some data, filix-tannic acid possesses pharmacological action. 12) Essential oil; is found in fresh, summer-dried rhizomes in an amount of 0.025%, and in autumn-dried ones in an amount of 0.04–0.045%; it contains peculiar fatty acids and esters of higher fatty acids (hexyl and octyl); there are indications of a therapeutic effect of the oil. 13) Fatty green oil (5–6%), passing from the rhizome into the ethereal extract; consists of glycerides of palmitic, cerotic, and oleic acids; a pharmacological action is also attributed to it. 14) Sugar (10%). 15) Starch. 16) Mineral salts (3%). 17) Filix wax. 18) Filix resin. Action and use. Despite the fact that a pharmacological effect is attributed to the majority of fern substances, it must be considered most reliable that only filmaron, amorphous fern acid, essential and fatty oils, and filix-tannic acid possess this effect. The rhizome of the male fern and its preparations are the most effective remedies against tapeworms, mainly against the broad tapeworm, as well as against the armed, unarmed, and dwarf tapeworms; they are also used for ancylostomiasis. The fern is a neuro-muscular poison for invertebrates (worms, crustaceans, mollusks, echinoderms, etc.); fern acid has the most pronounced effect; cat tapeworms die in a 0.01% solution of this acid. According to experiments by Yagi, after subcutaneous injection of fern acid to an earthworm, tone is immediately lost and paralysis of the nearest segments of smooth musculature appears; nerve trunks perish later; as the poison is absorbed, the paralysis spreads to the entire body of the worm; Ascaris resist the action of fern acid, but perish after its injection into the body thickness. During the therapeutic use of fern preparations, complete death of the worms usually does not occur; there is apparently only a depression of their neuromuscular apparatus. According to Dixon and Clark, pure fern acid does not have a pronounced effect on Taenia; these authors suggest that the presence of essential oil in the commercial extract, which dissolves this acid, increases its activity; it is possible that the presence of all active principles in the extract is a necessary condition for obtaining a therapeutic effect in humans (Dixon).

The question of the fate of fern substances in the organism is controversial. According to Heffter and Clark, powdered substances from the fern are sparingly soluble and almost unabsorbed in the intestine; however, soluble alkaline compounds of these principles may form in the latter, which, entering the blood, can produce a general effect; such an effect is also possible upon the administration of pure fern acid due to the ensuing intestinal irritation. The regimen in fern treatment, as in any anthelmintic treatment, should, without exhausting the patient, reduce the intestinal contents to a minimum and thereby ensure a more reliable effect of the remedy on the parasite: after two days of a liquid but nutritious diet, a laxative is given in the evening. On the next day, in the morning on an empty stomach, a fern preparation is prescribed. To expel the stunned worms from the intestine, 1¹/₂-2 hours after taking the fern, a laxative is given; in doing so, it is better not to use castor oil: it dissolves the active principles of the fern, the latter are absorbed into the blood and can produce a toxic effect; according to Clark, 57% of poisoning cases are related precisely to the aforementioned method of therapy. Instead of castor oil, in anthelmintic treatment in general, it is better to prescribe saline laxatives (MgSO₄, Na₂SO₄), calomel, senna leaves, licorice powder. Fern is often prescribed together with the indicated remedies. Fern poisoning occurs in an acute form. Aside from the indicated cases of treatment of fern with castor oil, the causes of poisoning can be very large doses of fern preparations, non-observance of intervals in treatment; apparently there are some other conditions for the retention of fern substances in the intestine which promote absorption into the blood (see above); as factors predisposing to poisoning, anemia and alcoholism are noted. Poisoning manifests as irritation of the gastrointestinal tract (vomiting, bloody diarrhea, abdominal pain), cyanosis, dyspnea, palpitation, albuminuria, dizziness, drowsiness, muscle twitching and weakness, convulsions, and finally collapse, loss of consciousness, coma, and death from paralysis of the respiratory center. In some cases, unilateral or bilateral amblyopia and amaurosis due to inflammation or atrophy of the optic nerve were noted; phenomena of jaundice are frequent in connection with degenerative-inflammatory changes in the liver or from the destruction of erythrocytes. Cases of acute yellow atrophy of the liver, as well as acute enlargement of the spleen after the use of fern, are known. The indicated phenomena can be obtained experimentally from the administration of fern acid to animals. Fern has a cumulative effect. Measures of combat: gastric lavage, laxatives, demulcents, and symptomatic therapy. Preparations. 1. Rhizoma Filicis maris (State Pharmacopoeia VII) is used in the form of a powder; the latter according to State Pharmacopoeia VII must be dry, light green in color, with the taste and smell of the rhizome; browned powder is not used; it is kept for no more than 1 year in stoppered dark glass bottles. Doses for adults are 4.0-15.0 in 3-4 doses (every 15 minutes), for children 2.0-3.0. 2. Extractum Filicis maris (aethereum) (State Pharmacopoeia VII)—the most commonly used fern preparation; it is a thickish mass of dark green color, with an unpleasant scratching taste; it is immiscible with water, soluble in ether; the extract must not have the odor of ether; it contains all fern substances (see above); upon standing of the extract, some active principles settle to the bottom: before dispensing from the pharmacy, such an extract must be mixed; it is stored in the cold, protected from light, with caution. The content of active substances (according to State Pharmacopoeia VII) must equal 26-28% (so-called crude filicin). In general, commercial extracts may contain substances varying in quantity and quality, which affects the potency; thus, for example, fern acid in the extract may be 2-3% (Boehm, Kraft) and 5-10% (Hausmann), flavaspidic acid 11-18% (Hausmann) and 2.5% (Kraft), etc. The quality of the extract (as well as the rhizome) is determined by biological and chemical methods, but neither of them satisfies the requirements of verification, because, on the one hand, our information on the active substances is insufficient and unreliable, the amount of inactive and toxic substances in the rhizome and extract is fluctuating, unequal, and finally, upon storage of the rhizome and preparations from it, their composition and action change greatly. Still, both biological and chemical tests are provisionally accepted. The biological method was developed by Yagi and is performed on earthworms [there is also a determination method proposed by Wasicky on small fish]; the method of Yagi and Wasicky is taken as the basis for the standardization method of male fern preparations adopted at the II International Conference on the Biological Standardization of Certain Drugs (Geneva, 1925). The chemical method has only relative significance and consists in the quantitative determination of active principles in the extract (so-called crude filicin); State Pharmacopoeia VII adopted the Fromme method: treatment of the ethereal solution of the extract with barium hydroxide, acidification of the aqueous layer of the resulting mixture and shaking it with ether, drying and weighing of the ethereal extract; its weight should be 1.04-1.12 (when using 5.0 of the extract), which corresponds to an active substance content of 26-28%; extracts with a smaller amount of these principles are not used, but go to dilute stronger extracts. Besides the indicated tests, there is a number of reactions for impurities. The maximum single dose (pro die) is 8.0; the most frequent prescription for adults is 4.0-6.0, for children 2.0. It is used in pills, gelatin capsules, emulsions, mixtures, and electuaries; to avoid the accumulation of fern substances in the intestine and thereby the possibility of poisoning, in case of failure of the first treatment, the second is performed no earlier than in three days. In recent years, the outpatient method of administering fern extract using a duodenal tube has become very widespread; according to the reviews of some clinicians, this method yields an almost 100% success rate, requiring a relatively small dose of the extract; the latter is administered (after preliminary dietary preparation) through a tube in the form of an emulsion of the following composition, for example: Extr. Fil. mar. aeth., Mucil. Gummi arabici aa 5.0, Natr. carbon. 0.5, Aq. dest. ad 50.0; immediately following the emulsion or 1 hour later, a laxative is poured in (e.g., 50 cm³ of a 50% warm solution of sodium sulfate); in some cases, ³/₅ to ⁴/₅ of the indicated dose of the extract is sufficient. 3. Filmaron; is obtained from the ether extract by heating with water and treating with an alkaline-earth metal (properties—see above). Doses: 0.5-0.7; a solution of filmaron in castor oil (1:10) or in an indifferent vegetable oil, so-called Filmaronol, 7.0-10.0 in 2 doses with intervals of 30 minutes, is also often used. One hour after the last dose, a laxative is given to avoid side effects. 4. Fern acid (Acid. filicicum) is used rarely (0.3-1.0).