Silybum marianum

This plant, syn. Carduus marianus (Compositae) is one of the milk-thistles. Indigenous to the Mediterranean region, it has been introduced to most areas of Europe, North and South America and Southern Australia. In addition to cultivation as a medicinal crop the plant is grown as an annual or biennial for its attractive foliage. The glabrous leaves are dark green, oblong sinuate-lobed or pinnatifid, with spiny margins. White veins give the leaves, which initially form a flat rosette, a diffusely mottled appearance. The terminal heads which appear from July to September are also spiny with deep violet and slightly fragrant flowers. The achenes, 6–7 mm in length and transversely wrinkled, are dark in colour, grey-flecked with a yellow ring near the apex. Attached to the achene is a long white pappus.

G. Ram et al. (Fitoterapia, 2005, 76, 143) studied 15 accessions of the plant and suggest that an improved crop (seed yield/plant, number of capsules/plant) could be obtained by direct selection.

As a bitter the milk-thistle has a long history but more recently it has become recognized in Germany and continental Europe as a most effective liver remedy, particularly in those forms of hepatitis affecting the liver parenchyma.

Milk-thistle fruit

BP/EP, BHP 1996 consists of the mature fruit, devoid of pappus, of Silybum marianum L. Gaertner. Several so-called flavanolignans with marked hepatoprotective properties have been isolated from the fruits. A mixture of these, termed silymarin, is available commercially as a dried, purified and standarized extract. Principal components of the extract are three pairs of diastereoisomers: silybin (silibinin) A and silybin (silibinin) B, isosilybin (isosilibinin) A and isosilybin (isosilibinin) B and, silychristin (silicristin) and silychristin (silicristin) B; see Fig. 29.2 for formulae. Other related constituents are silandrin, 3-deoxysilychristin, silymonin and silydianin. A new compound, silyamandin, has recently been isolated from incubated tincture of milk thistle; it may arise from the degradation of silydianin (Fig. 29.2) (S. L. Mackinnon et al., Planta Medica, 2007, 73, 1214). The literature nomenclature for these compounds can be confusing as recommended international proprietary names (in brackets above) may also be used and both nomenclatures still appear to be used by authors. For isolation and structural reports on the above see DY-W. Lee and Y. Liu, J. Nat. Prod., 2003, 66, 1171, 1632; W. A. Smith et al., Planta Med., 2005, 71, 877. The levels of these flavonolignans vary markedly in samples of S. marianum from different sources; they are formed by various couplings of the flavonoid taxifolin and the lignan precursor coniferyl alcohol. Silymarin, in addition to the above flavonolignans, contains 20–30% of polyphenolic compounds. The scavenging (antioxidant) properties of the silymarin components have been tested against phenylglyoxylic ketyl radicals (F. Sersen et al., Fitoterapia, 2006, 77, 525).

Fig. 29.2 Constituents of milk-thistle fruit.

Other non-specific constituents reported for the fruits involve flavonoids including taxifolin, sterols, dehydrodiconiferyl alcohol and fixed oil based principally on linoleic and oleic acids.

Silybin-like metabolites have been isolated from cell suspension cultures and although, to date, no glycosides of silybin have been reported in the plant, silybin-7-O-β-D-glucopyranoside can be produced by cell cultures of Papaver somniferum var. setigerum with added silybin (V. Kren et al., Phytochemistry, 1998, 47, 217.

The BP/EP test for milk-thistle fruit identifies silybin, silychristin and taxifolin and the liquid chromatography assay involves separation of the flavonolignans, summation of their peak areas and calculation of their total content in the drug by use of a reference solution of the same constituents; absorbance measurements are made at 282 nm.

Apart from the established use of silymarin as an antihepatotoxic agent, recent research together with clinical studies, have shown the flavonolignans to have anticancer properties (see Chapter 27).

For a 1995 extensive review of the drug (211 refs) see P. Morazzoni and E. Bombardelli, Fitoterapia, 1995, 66, 3.

Cynaria scolymus (Asteraceae/Compositae)

The leaves of the globe artichoke have been described in Chapter 19, the drug being used principally as a cholagogue (stimulation of bile production in the liver and promotion of emptying of the gall bladder and bile ducts). There has been more recent interest in the hepatoprotective properties of the plant and significant antioxidative activity has been demonstrated involving chlorogenic acid and cynarin; other constituents are, however, also implicated. For further details and references, see J. Barnes et al., Herbal Medicines, 3rd ed., 2007, p. 67. Pharmaceutical Press, London.

Peumus boldus

Boldo leaves (BP/EP; BHP 1996) are collected from the small tree Peumus boldus Molina (Monimiaceae) indigenous to Chile. The leaves are up to about 8 cm long, of coriaceous texture with a strong camphoraceous lemony odour owing to the presence of volatile oil (2%) containing ascaridole, linalool, p-cymene and cineole. E. Miraldi et al. (Fitoterapia, 1996, 67, 227) identified 46 components of the oil, 22 of which were recorded for the first time in P. boldus. The active constituents have been shown by laboratory testing to be alkaloids of the aporphine type (1–3%) the chief of which is boldine (Fig. 29.1).Boldine is reported to be a potent scavenger of hydroxyl, lipid and alkyl peroxyl radicals and experimental evidence supports its cytoprotective and anti-inflammatory properties (M. Gotteland et al., Planta Medica, 1997, 63, 311).

Studies on the genetic variation of the essential oil and alkaloid composition of the drug (H. Vogel et al., Planta Medica, 1999, 65, 90) indicated no significant differences in boldine concentration in samples from North, Central and South Chile; highest values for ascaridole were in northern collections and for p-cymene in the southern ones. There appeared to be considerable potential for the selection of superior strains. The BP requirement for volatile oil is not more than 2.0% (whole drug) and 1.5% (fragmented drug), and for alkaloid content (as boldine), not less than 0.1%. Reticuline and flavonoid glycosides have also been recorded. The bark, which contains a higher content of alkaloids (6–10%), is exported from Chile for the commercial production of boldine.

The leaves have a stimulant action on the liver and diuretic properties. An extract of the total alkaloids has a greater activity than boldine itself. The drug is also used in proprietary slimming preparations.

Taraxacum officinale root (Compositae). Syn: Dandelion root

Although now obsolete as a drug in the allopathic system of medicine dandelion root has maintained its importance in herbal medicine in which it is used as a hepatic stimulant, diuretic, tonic and antirheumatic. Commercial supplies of the cultivated drug come principally from Eastern Europe.

The drug consists of the dried vertical rhizome and tap-root which pass imperceptibly into one another. Up to 30 cm long when fresh and2.5 cm diameter, it is frequently branched with an apical crown bearing brownish hairs. The rhizome has a ring of vascular bundles and a pith; the root has a central yellow wood. Concentric zones of latex vessels occur in the thick bark. Dandelion root contains up to 25% of inulin and other polysaccharides, sesquiterpene lactones including taraxacoside, triterpenes including taraxerol, taraxol and B-amyrin, various acids including caffeic and p-hydroxyphenylacetic acids, and carotenoid yellow colouring matter.

In addition to its use in medicine the dandelion root is useful botanically for the demonstration of latex vessels (Fig. 42.7) and inulin (Fig. 42.1). The leaf has similar medicinal uses. Flavonoids, cinnamic acids and coumarins from different plant tissues and medicinal preparations have been recorded (C. A. Williams et al., Phytochemistry, 1996, 42, 121). For a review of the phytochemistry and pharmacology of the drug (over 90 refs + formulae), see K. Schultz et al., J. Ethnopharmacol. 2006, 107, 313.

Other drugs used to treat liver ailments as exemplified by the BHP (1983, 1991) and R. F. Weiss (1988, Herbal Medicine Ab Arcanum, Gothenberg, Sweden; Beaconsfield Publishers Ltd, Beaconsfield, UK), are listed below:

Chionanthus virginicus (Oleaceae)

Bark a cholagogue and hepatic stimulant.

Euonymus atropurpureus (Celastraceae)

Bark is used in combination with other drugs for the treatment of gall bladder and liver disorders; it is essentially a cholagogue.

Fumaria officinalis (Fumariaceae), syn. Common fumitory

The whole herb, which also features in a number of commercial Indian preparations, is used for liver disorders; it contains isoquinoline alkaloids including canadine, dicentrine, fumaricine and sanguinarine.

Hydrastis canadensis (Ranunculaceae)

The root is employed in atonic dyspepsia with hepatic symptoms. A fuller description of the drug is given in Chapter 26.

Iris versicolor and Iris caroliniana (Iridaceae), syn. Blue flag

The rhizome is used for biliousness with liver dysfunction.

Juglans cinerea (Juglandaceae), syn. White walnut, Butternut

The inner bark contains naphthoquinones including juglone together with fixed oil, volatile oil and tannins. Extracts are used for various conditions including use as a cholagogue.