Silibinin (INN) (silybin, Legalon®) is the major active constituent of silymarin, the mixture of flavonolignans extracted from blessed milk thistle (Silybum marianum). It is used in treatment and prevention of liver diseases because of its hepatoprotective (antihepatotoxic) properties. Clinical tests showed also its ability to protect against certain types of cancer (skin and prostate), probably due to its antioxidant properties.

Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (Legalon SIL®) (injection solution) is used in treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning.

Poor water solubility and bioavailability of silymarin led to development of enhanced formulations. Silipide (Siliphos®), complex of silymarin and phosphatidylcholine (lecithin), is about ten times more bioavailable than silymarin. It has been also reported that silymarin inclusion complex with β-cyclodextrin is much more soluble than silymarin itself. There have also been prepared glycosides of silybin, which showed better water solubility and even stronger hepatoprotective effect.

The acute toxicity of silymarin and silybin were investigated by oral and intravenous route in various animal species. No mortality or any signs of adverse effects were observed after silymarin at oral doses of 20 g/kg in mice and 1g/kg in dogs. The 50% lethal dose (LD50) after intravenous infusion values are 400 mg/kg in mice, 385 mg/kg in rats and 140 mg/kg in rabbits and dogs. These data demonstrate that the acute toxicity of silymarin is very low. Similarly, its subacute and chronic toxicity are very low; the compound is also devoid of embryotoxic potential.

Silymarin, as other flavonoids, has been shown to inhibit P-gp-mediated cellular efflux. The modulation of P-gp- activity may result in altered absorption and bioavailability of drugs that are P-gp- substrates. It has been reported that silymarin inhibit cytochrome P450 enzymes and an interaction with drugs primarily cleared by P450s cannot be excluded.

References

• Morazzoni P., Bombardelli E. (1994). Silybum marianum (cardus marianus) Fitoterapia 66:3-42.
• Saller R., Meier R., Brignoli R. (2001) The use of silymarin in the treatment of liver diseases. Drugs, 61(14), 2035-63.