Milk Thistle

(Silybum Marianum)

Michelle Giesler and Kimberly Jones

General Description

• Other names: Marian thistle, St. Mary's thistle, Our Lady's thistle
• Family: Asteraceae
• Distribution: Native to the Mediterranean region of Europe, but naturalized in California and the eastern US

Description of plant:

• tall herb with prickly leaves and a milky sap
• Small, hard fruits (achenes), a feathery tuft or pappus is removed
• Milk white veins in the leaves (originated in the milk of the Virgin Mary which once fell upon the plant)

Parts used:

• ripe fruit (not seeds), root, leaves, hull

Chemical composition

• Silymarin- chemical mixture of antihepatotoxic principles; 1-4% conc. in fruit
• Shown to consist of a large number of flavonolignans, including principally silybin accompanied by isosilybin, dehydrosilybin, silydianin, silychristin, etc.

History and folk use

• Formerly frequently cultivated in gardens
• The stalks may be eaten and are palatable and nutritious
• Young leaves may be eaten as a salad, and were sometimes baked in pies
• The heads were formerly boiled and eaten, treated like those of an Artichoke
• Thought to be a great breeder of milk and proper diet for nursing women
• Thought to have a healing property in those with snake bites
• If worn around the neck it would protect you from snake bites
• Fruit formerly thought to cure hydrophobia
• Applied externally, said to have been proven beneficial in cases of cancer
• The young, tender plant be boiled and eaten in the spring as a blood cleanser
• Fruits have been used for many years for a variety of conditions, especially liver complaints. However, medicinal use of the plant, except as a simple bitter, was practically discontinued early in the twentieth century.

Primary effects in the body

• Acts on cell membranes of liver cells to prevent the entry of toxic substances
• Stimulates protein synthesis, accelerating regeneration process & production of liver cells
• Acts as an antioxidant, with far greater free radical damage control than vitamin E
• It may offer some protection against toxic side effects from acetaminophen

Clinical applications

• Early treatment for chronic liver problems
• Rehabilitation from alcohol, solvent or IV recreational abuse
• Protects hepatocytes from heavy metal, chemical and alcohol injury
• Limits fatty degeneration and speeds up hepatitis recovery, slowing or reversing cirrhosis
• Supportive treatment for inflammatory liver conditions and cirrhosis

Toxicity

• None reported

Drug and disease interactions

• None reported

Dosage

• Fruit (seeds): 2-3 capsules up to 3 x day
• Tincture: 1:5, 60% alcohol, ½ to 1 teaspoon up to 4 x day (equal parts of root & seed with hull attached)
• Silymarin is very poorly soluble in water so is not effective as a tea (< 10% plant activity)
• Poor solubility and poor absorption from GI tract (20-50%) make active principles best administered parenterally
• Oral use requires a concentrated product
• Capsules containing 200mg of a concentrated extract representing 140mg of silymarin

Primary and Tertiary literature

Protection from Amanita phalloides intoxication Tox Appl Pharm 73 (1984)

• Severe poisoning with mortality rate of 30%
• Study in beagles
• 50 gm/kg silibinin 5 and 24 hrs post-intoxication
• 4 deaths in control group / 0 deaths with silibinin
• Reduction in elevations of GPT, GOT, AP and bilirubin with silibinin; less decrease in PT
• Mechanism of Action?
  • Modification or occupance of cell membrane receptor sites
  • Decrease phospholipid metabolism
  • Prevention of inhibition of RNA Polymerase and RNA synthesis by toxin

Increase of Glutathione Content in the Liver Planta Medica 55 (1989)

• 200 mg/kg silymarin single dose
• Over 50% increase GSH in liver and intestine
• Selectivity
  • accumulation principally in liver
  • entero-hepatic recirculation
• An increase in GSH can increase conjugation/elimination of toxins and decrease lipid peroxidation
• Mechanism of action?
  • Increase in membrane permeability of amino acids involved in GSH synthesis

Stimulation of DNA synthesis in malignant cell lines? Biochem Pharm 35(1986)

• 27 mg/kg silibinin prior to injection of radioactive thymidine
• Silibinin increases ribosomal RNA synthesis
• No influence on DNA synthesis in normal livers
• Large increase in DNA synthesis in hepatectomized rats / 23-35% increase in thymidine incorporation
• No influence on DNA synthesis in fast growing hepatoma cell cultures
• Mechanism of action?
  • Hepatectomized rats
    • If the regulatory signal for replication initiation is given, increase in rRNA and protein synthesis also accelerates DNA synthesis
  • Hepatoma cells
    • The rate of proliferation is already maximal and cannot be further intensified

Effect of silibinin on biliary lipid composition Journal of Hepatology 12(1991)

• The rats
  • 100mg/kg or 50mg/kg silymarin for 7 days
  • measured biliary cholesterol, biliary phospholipid, total bile salt and bile flow
  • decrease in biliary cholesterol and phosolipid
  • no change in bile flow and total bile salts

• The Humans
  • 400mg/day silymarin in cholecystectomized and gallstone patients for 1 month
  • significant decrease in biliary cholesterol for both groups

• Mechanism of Action?
  • Found a dose dependent decrease in HMG-CoA reductase in the liver with increasing silymarin concentration
  • A decrease in HMG-CoA reductase leads to a decrease in synthesis of cholesterol