El control con aprendizaje por imitación

The fresh bark contains free anthrones and must be stored for at least 1 year or artificially aged by heat or aeration before therapeutic use (1, 11, 12).

General appearance

Single or double quills, rarely in channelled pieces; usually 15 cm long, 0.5–

2 cm wide and extremely thin (not more than 2 mm thick). Outer surface greyish-brown or purplish-black, wrinkled, with numerous transversely elon-gated whitish lenticels; sometimes bearing patches of foliaceous lichen, with small black apothecia; when gently scratched, crimson colour of inner layers of cork becomes evident. Inner surface reddish-yellow to dark brown; fine longi-tudinal striations, becoming red when moistened with dilute solutions of alkali (Bornträger’s test). Fracture, short in the outer part and slightly fibrous in the inner part (1, 2).

Organoleptic properties

Odour: characteristic; taste: sweetish then slightly bitter and astringent;

mucilaginous (1, 8).

Microscopic characteristics

Cortex yellowish-brown, consisting of thin-walled parenchyma, containing scattered cluster crystals of calcium oxalate and few small starch grains, and showing large cells filled with mucilage and few groups of slightly lignified fibres, each up to 40 mm wide. Phloem yellowish-brown, traversed by numer-ous, somewhat wavy medullary rays, 1–3 cells wide and 10–25 cells high, and showing numerous tangential groups of strongly lignified bast fibres, accom-panied by prismatic crystals of calcium oxalate, forming a crystal sheath around each group; individual fibres 12–24 mm in diameter (1).

Powdered plant material

Yellowish-brown. Fragments of reddish-brown cork; fragments of groups of lignified bast fibres, accompanied by a calcium oxalate crystal sheath; occa-sional fragments of slightly lignified fibres; fragments showing cells of medullary rays, with yellow contents which turn red with solutions of alkali or with sodium hypochlorite solution; cluster crystals of calcium oxalate, 10–

25 mm in diameter; prismatic crystals of calcium oxalate, 7–15 mm long; few starch grains 3–10 mm in diameter; sclereid cells absent (1, 2).

General identity tests

Macroscopic, microscopic and microchemical (Bornträger’s test) examinations and thin-layer chromatography for characteristic hydroxyanthracene glycosides (1, 2).

Purity tests

Tests for specific microorganisms and microbial contamination limits are as described in the WHO guidelines on quality control methods for medicinal plants (13).

Foreign matter Not more than 1% (2).

Total ash

Not more than 6% (2).

Acid-insoluble ash Not more than 2% (1).

Loss on drying Not more than 10% (2).

Pesticide residues

The recommended maximum limit of aldrin and dieldrin is not more than 0.05 mg/kg (14). For other pesticides, see the European pharmacopoeia (14), and the WHO guidelines on quality control methods for medicinal plants (13) and pesticide residues (15).

Heavy metals

For maximum limits and analysis of heavy metals, consult the WHO guidelines on quality control methods for medicinal plants (13).

Radioactive residues

Where applicable, consult the WHO guidelines on quality control methods for medicinal plants (13) for the analysis of radioactive isotopes.

Other purity tests

Chemical, sulfated ash, water-soluble extractive and alcohol-soluble extractive tests to be established in accordance with national requirements.

Chemical assays

Contains not less than 7.0% of glucofrangulins, calculated as glucofrangulin A, determined by spectrophotometry at 515 nm (2). The high-performance liquid chromatography method reported for quantitative analysis of cascarosides (16) can also be considered.

Major chemical constituents

The active constituents are hydroxyanthraquinone glycosides (3–8%) consist-ing of monoglycosides and diglycosides of frangula emodin, with the diglyco-sides, glucofrangulins A and B, being the major compounds. The major monoglucosides are frangulins A and B (17). Other anthranoid derivatives present include emodin anthrone-6-O-rhamnoside (franguloside), as well as physcion and chrysophanol in glycosidic and aglycone forms (17, 18). In the fresh bark, anthraquinones are not present, but exist as their reduced anthrone and dianthrone glycosides, which are converted by oxidation during drying and storage, or by accelerated heat and air treatment (4, 6, 8, 9, 17). The structures of the major anthraquinone glycosides, free anthraquinones and frangula emodin anthrone are presented below.

OH O O

D-apio-β -^D-furanosyl β -^D-glucopyranosyl 6-deoxy-α -^L-mannopyranosyl O

H3C

OH O OH

OH

frangula emodin anthrone

Medicinal uses

Uses supported by clinical data

Short-term treatment of occasional constipation (1, 9–11). As a single dose, for total intestinal evacuation before X-rays and other diagnostic examinations when electrolyte solutions alone are insufficient for adequate evacuation or the use of electrolyte solutions is not possible (11).

Uses described in pharmacopoeias and in traditional systems of medicine

As a cathartic (1).

Uses described in folk medicine, not supported by experimental or clinical data

Internally for treatment of diabetes and externally for skin irritations (6).

Experimental pharmacology Laxative effects

The pharmacological effects of Cortex Frangulae are associated with the hydroxyanthraquinone glycosides, glucofrangulins A and B, and frangulins A and B (17). After oral administration of Cortex Frangulae, the hydroxyan-thracene glycosides are not absorbed in the upper intestine, but are hydrolysed in the colon by intestinal bacteria to form the pharmacologically active metabo-lites. These metabolites are partially absorbed in the colon and act as a stimu-lant and irritant to the gastrointestinal tract, as does senna (11, 18, 19, 20). The mechanism of action, similar to that of senna, is twofold. Firstly, there is stimu-lation of colonic motility, resulting in augmented propulsion, and accelerated colonic transit (which reduces fluid absorption from the faecal mass). Secondly, there is an increase in paracellular permeability across the colonic mucosa, probably due to inhibition of sodium/potassium-transporting adenosine triphosphatase or inhibition of chloride channels (18, 21). The increased per-meability results in increased water content in the colon (11, 21).

The laxative effect of Cortex Frangulae is not generally observed until 6–8 hours after oral administration. Hydroxyanthracene glycosides are excreted predominantly in the faeces but are also excreted to some extent in urine, pro-ducing an orange colour; anthrones and anthranols will also pass into breast milk (18).

Toxicity and overdose

As with other anthraquinone laxatives, the major symptoms of overdose are gripes and severe diarrhoea with consequent loss of fluid and electrolytes (22).

Treatment of overdose should be supportive with generous amounts of fluid.

Electrolyte levels should be monitored, particularly those of potassium. This is especially important in children and the elderly (22).