SILYMARIN: IS IT A TRITON AMONG THE MINNOWS?

*Dr. Bushra Hasan Khan, Dr. Jameel Ahmad, Prof. Farida Ahmad and Prof. Syed Mobashir Yunus.

ABSTRACT

The flavonoid silymarin has documented hepatoprotective properties. The mechanisms of action are still poorly understood. However, the data in the literature indicate that silymarin acts in four different ways: as antioxidants, scavengers and regulators of the intracellular content of glutathione; as cell membrane stabilisers and permeability regulators that prevent hepatotoxic agents from entering hepatocytes; as promoters of ribosomal RNA synthesis, stimulating liver regeneration; and as inhibitors of the transformation of stellate hepatocytes into myofibroblasts. The key mechanism that ensures hepatoprotection appears to be free radical scavenging. Anti-inflammatory and anticarcinogenic properties have also been documented. Silymarin is able to neutralise the hepatotoxicity of several agents, including Amanita phalloides, ethanol, paracetamol (acetaminophen) and carbon tetrachloride in animal models. Hepatoprotection has been documented by improvement in liver function tests; moreover, treatment with silymarin was associated with an increase in survival in a placebo-controlled clinical trial in alcoholic liver disease. Pharmacokinetic studies have shown that silymarin is absorbed by the oral route and that it distributes into the liver, stomach, intestine, and pancreas. It is mainly excreted as metabolites in the bile, and, is subject to enterohepatic circulation. Toxicity is very low, the oral 50% lethal dose being 10,000 mg/kg in rats and the maximum tolerated dose being 300 mg/kg in dogs. Moreover, silymarin is devoid of embryotoxic potential. In conclusion, silymarin is a well-tolerated and effective antidote for use in hepatotoxicity produced by a number of toxins. Numerous experimental studies suggest that it acts as a free radical scavenger, with other liver-specific properties that make it a unique hepatoprotective agent.

Keywords: Silymarin, Hepatoprotective, Carbon tetrachloride.