Samarin Mechanism of Action

Pharmacodynamics: Mechanism of Action: Silymarin, a flavonoid extract of milk thistle, is extracted from the seeds and fruit of Silybum marianum and in reality is a mixture of three structure components: silibinin, silydianine and silychristine. Silymarin has been shown to have hepatoprotective actions against chemical, infectious and environmental toxins. It has antioxidant, antihepatitis and anticirrhotic effects.
Flavonoids including Silymarin are good antioxidants due to their phenolic structure. They also act as plasma membrane stabilizer.
Silymarin is an antioxidant free-radical scavenger. It was postulated that free-radical scavenger and antioxidant activity of silymarin may be the mechanism of hepatotoxicity protection.
Silymarin is thought to protect the liver by altering the liver cell's outer membrane thus inhibiting the entrance of various toxins and blocking toxin-binding sites.
Silymarin influences the cell membranes, prohibiting the inflow of cell toxins like amanitin and phalloidin as well as loss of cell constituents (transaminases, potassium) from the cell body. This "stabilization" of cell membranes is supported by the antiperoxidative properties of silymarin, which is related to its radical scavenger. Thus, the pathophysiological cycle of lipid peroxidation responsible for damaging membranes is interrupted.
Silymarin increase intracellular concentrations of glutathione which is used by many detoxification systems in liver cells.
Silymarin inhibits lipid peroxidation of hepatocyte, microsomal, and erythrocyte membranes as well as increasing hepatocyte protein synthesis via stimulation of ribosomal RNA and increased regenerative capacity of liver cells. Furthermore, silymarin leads to increased formation of ribosomal RNA by stimulating the activity of RNA - polymerase I in the nucleus.
Silymarin is thought to exert an antiinflammatory response via inhibition of leukotriene production. This anti-inflammatory effect may be beneficial in treating liver cirrhosis or fibrosis.
Silymarin is used for the treatment of numerous liver disorders characterized by degenerative necrosis and functional impairment. Silymarin has been documented in clinical trials in terms of improvement of liver function.
Pharmacokinetics: Silymarin is not soluble in water, absorption after oral administration is rather poor. In human, the proportion absorbed from the intestine, as measured from renal and biliary elimination, was between 20%-40% of a single dose of 140 mg Samarin. Absorption is rapid with maximum biliary excretion reached in human subjects between 2 and 4 hours. After repeated therapeutic doses of Samarin (140 mg 3 times a day), the levels of silibinin found in human bile are the same as after a single dose. This finding shows that silibinin has no tendency to accumulate.
Peak plasma concentrations are achieved in 4 to 6 hours.
Silymarin is mainly excreted in the bile (>80% of the amount absorbed) and, to a lesser degree, in the urine. Its elimination half-life ranges from 6 to 8 hours. Silymarin and other components of silymarin are rapidly conjugated with sulfate and glucuronic acid in the liver. The conjugate pass into the plasma and into the bile, where they are found in amounts corresponding to 80% of the total dose administered. The metabolites detected in the bile are glucuronides and sulfates.