Materia Medica

Silybum marianum
BY KERRY BONE

Also know as Carduus marianus

Common Names: St Mary's Thistle, Milk Thistle (due to the white markings on the leaves), Variegated Thistle Family: Asteraceae Part Used: Seed

It protects against the uptake of some toxins by the hepatocyte,13 and may also stabilise the hepatocyte cell membrane.14 Silymarin stimulates protein synthesis in the cell which is an important step in the repair phase of liver damage.15

Active Constituents
Flavanolignans (1 to 3%) collectively known as silymarin.1 Individual components of silymarin are mainly silybin, silydianin and silychristin.1 The flavanolignans are often incorrectly classified as flavonoids. The seeds also contain 20 to 30% fixed oil which can give liquid extracts a milky colour. Other components include flavonoids and saponins.

Pharmacological Studies
Hepatoprotective Activity
• Silymarin and isolated silybin have both shown protective activity against acute administration of liver toxins such as carbon tetrachloride,2 galactosamine,3 ethanol,4 paracetamol,5 and the toxin of the Death Cap mushroom (Amanita phalloides).6 Similar protective activity has also been demonstrated against chronic administration of carbon tetrachloride,7 heavy metals,8 thioacetamide9 and several drugs.10

Anticholestatic Activity
• Silybin demonstrated anticholestatic activity against paracetamol- and ethynylestradiolinduced cholestasis by countering the reduction in bile salt output and bile flow.11

Mechanisms of Action
• Silymarin has pronounced antioxidant activity,12 and therefore protects against oxidative damage to the hepatocyte.

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Materia Medica

Toxicology
• The acute toxicology of silymarin is very low. Oral doses of 20 g/kg in mice and 1 g/kg in dogs resulted in no mortality or any signs of adverse effects.16 Long-term studies also failed to demonstrate toxicity or teratogenic effects.16

treatment with silymarin significantly reduced mortality.23 This effect was more pronounced in patients with alcoholic cirrhosis.

Toxic Damage of Different Origins
• In an open study on 2000 patients suffering from toxic liver damage of differing aetiologies, serum levels of hepatic enzymes were considerably reduced.22 Symptoms such as nausea, discomfort and skin itching were also improved in 83% of patients.

Pharmacokinetics
• • Components of silymarin are mainly excreted in the bile as hepatic conjugates.17 In cirrhotic patients the pharmacokinetic parameters were comparable to those of healthy subjects with maximum serum concentrations ranging from 0.02 to 0.12 µg/mL.18

Poisoning with Amanita phalloides
• Intravenous infusion of silybin, in combination with normal management techniques, induced a marked reduction in mortality in a multi-centre study on 252 cases of intoxication by Amanita phalloides.24

Clinical Studies
Alcoholic Liver Disease
• In a double blind study, patients with cirrhosis were treated with 420 mg of silymarin per day for six months (3 tablets each containing 140 mg).19 Serum levels of hepatic enzymes and bilirubin were significantly reduced compared to placebo.19 These improvements were accompanied by positive histological changes in the livers of patients receiving silymarin.19 Significant antioxidant activity was verified in a double blind clinical trial involving 36 patients with alcoholic liver disease.20 Diabetes secondary to alcoholic cirrhosis also responded favourably to silymarin treatment in a randomized study on 60 patients.21 •

Chronic Hepatitis
In a double blind trial on chronic persistent hepatitis, silybin treatment for 3 months decreased liver enzymes.25 Silybin reduced the parameters related to hepatocellular necrosis in a short-term double blind study on chronic active hepatitis.26

Actions
Hepatoprotective, hepatic trophorestorative, choleretic, antioxidant.

Hepatotoxic Effects of Drugs and Chemicals
• Silymarin administered during the pre- and postoperative period prevented the increase of hepatic enzymes in the serum induced by the toxic effect of general anaesthesia.22 Silymarin also improved liver function in patients who had been exposed for many years to halogenated hydrocarbons.9

Cirrhosis of the Liver
• In a four-year double blind randomized study on 170 patients with cirrhosis of different aetiologies, it was demonstrated that long-term

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Materia Medica

Medicinal Uses
• • • • • • • • • • Alcoholic liver damage Liver damage or toxicity from any cause Chronic hepatitis of autoimmune or viral origin Acute hepatitis After-effects of liver infections Gall bladder symptoms Chemical, food or drug intolerances To improve liver function Low grade toxic effects of drugs or environmental pollutants, such as pesticides Fat intolerance, nausea or chronic constipation due to poor liver function

REFERENCES
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 Morazzoni, P and Bombardelli, E: Fitoterapia 66, 3 (1995) Vogel, G: Arzneim-Forsch 25, 82 (1975) Schriewer, H et al: Arzneim-Forsch 25, 1582 (1975) Valenzuela, A et al: Biochem Pharmacol 34, 2209 (1985) Campos, R et al: Planta Med 55, 417 (1989) Floersheim, G L etal: Toxicol Appl Pharmacol 46, 455 (1978) Mourelle, M et al: Fundam Clin Pharmacol 3, 183 (1989) Barbarino, F et al: Rec Roum Méd-Méd Interne 19, 347 (1981) Leng-Peschlow, E and Strenge-Hesse, A: Z Phytotherapie 12, 162 (1991) Martines, G et al: Arch Sc Med 137, 367 (1980) Shukla, B et al: Planta Med 57, 29 (1991) Bindoli, A et al: Biochem Pharmacol 26, 2405 (1977) Münter, K et al: Biochim Biophys Acta 860, 91 (1986) Roberti, R et al: Pharmacol Res Commun 5, 249 (1973) Sonnenbichler, J and Pohl, A: Hoppe-Seyler's Z Physiol Chem 361, 1757 (1980) Hahn, G et al: Arzneim-Forsch 18, 698 (1968) Flory, P J et al: Planta Med 38, 227 (1980) Orlando, R et al: Med Sci Res 18, 861 (1990) Fehér J et al: Orv Hetil 130, 2723 (1989) Fehér J and Vereckei: Z Gastroenterol 29, 67 (1991) Velussi, M et al: Curr Ther Res 53, 533 (1993) Fintelmann, V: Med Klin 68, 809 (1973) Ferenci, P et al: J Hepatol 9, 105 (1989) Hruby, K and Csomós, G: 1st IGSC, Amsterdam (1989) Marcelli, R et al: Eur Bull Drug Res 1, 131 (1992) Buzzelli, G et al: Int J Clin Pharmacol Ther Toxicol 31, 456 (1993)

Contraindications and Cautions
• None known

Dosage and Administration
• • 3 to 5 g per day of seed or 3 to 5 mL of the 1:1 liquid extract. For more severe cases, such as advanced cirrhosis, a concentrated extract standardised for silymarin should be prescribed. A dose of 600 mg per day of 70:1 extract corresponding to 420 mg of silymarin has been used in several clinical trials. The absorption of silymarin is enhanced by lecithin, and simultaneous dosing with a lecithin supplement is recommended.

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Modern Phytotherapist 27

Clinical

Clinical Notes on Silybum marianum
BY NICHOLAS BURGESS

It is important to note that St Mary's Thistle is not the only method of treatment for the range of liver problems a practitioner may encounter in practice. I have attempted to give a brief outline below of the various circumstances which require some form of therapy for the liver. 1 A patient may need treatment to guard against the toxic threat to the liver from environmental or ingested substances, including prescribed drugs, alcohol and pollutants. This requires the action of hepatoprotective and probably in addition, hepatorestorative treatments. Herbs which fulfil this role include Silybum marianum (or the stronger Silymarin), Bupleurum falcatum, Picrorrhiza kurroa and Cynara scolymus. Patients who have had liver damage in the past due to environmental or ingested toxins or hepatitis will require a hepatorestorative. Herbs which fulfil this role are Silybum marianum, Schisandra chinensis and Bupleurum falcatum in combination with bitters and choleretics or cholagogues. Patients encountering ongoing destruction of hepatocytes from infectious or inflammatory origin need hepatoprotectives and hepatorestoratives, immune stimulants and specific antimicrobial therapy. A patient who has sluggish bowel function, constipation, headaches, period pain etc, the wholistic diagnosis for which is "liver congestion", requires a choleretic and

cholagogue. This will help get the bile flowing and both directly and indirectly assist in relieving congestion in the liver. Choleretic herbs, some with cholagogue function, include gentle agents such as Taraxacum officinale radix, Cynara scolymus, through to the stronger Berberis vulgaris, Chelidonium majus and Chionanthus virginicus. In short, when dealing with that umbrella concept in wholistic medicine of "treating the liver", there are several alternatives. It is necessary to take a good case history, make a diagnosis and decide on the actions required before choosing the herbs. While St Mary's Thistle is often helpful, it is not appropriate in all circumstances. See Kerry Bone's article on "Western Herbal Therapeutics" in this edition.

2

Mr Nicholas Burgess
DH, MNHAA

3

4

Nick Burgess is a medical herbalist and has been in practice for over ten years. He has lectured at Sydney's most prominent natural therapies colleges since 1985 and is a frequent guest speaker at seminars both in Australia and overseas. He is currently Vice-President of the National Herbalists Association of Australia and has been on the Board of Directors for six years.

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