St Mary’s thistle: Background. Actions

Common Name

St Mary’s thistle

Other Names

Carduus marianus, cardo bianco, cardo de burro, chandon marie, holy thistle, lady’s milk, lady’s thistle, Mariendistel, Marian thistle, Mary thistle, milk thistle, silybum, true thistle

Botanical Name / Family

Silybum marianum (family [Compositae] Asteraceae)

Plant Part Used

Ripe seed

Chemical Components

The major active constituents are the flavolignans, collectively named ‘silymarin’. The principal components of silymarin are silybin, isosilybin, silychristin and silydianin. Silybin makes up approximately 50% of silymarin and is regarded as one of the most biologically active constituents. There is also a fixed oil comprising linoleic, oleic and palmitic acids, tocopherol and sterols, including cholesterol, campesterol, stigmasterol and sitosterol.

Historical Note

St Mary’s thistle has a long history of traditional use since ancient times. Over the centuries, it has been touted as a remedy for snake bite, melancholy, liver conditions and promoting lactation. The name ‘milk thistle’ derives from its characteristic spiked leaves with white veins, which according to legend, were believed to carry the milk of the Virgin Mary.

St Mary’s thistle:  Main Actions

Most investigation has used standardised preparations of St Mary’s thistle, the silymarin constituent group or silybin.


Protection of liver cells has been demonstrated against the following substances in vitro or in vivo:

  • carbon tetrachloride-induced liver cirrhosis
  • paracetamol-induced liver peroxidation
  • cyclosporin
  • phenothiazine
  • butyrophenone
  • erythromycin
  • amitriptylineand nortriptyline
  • oestradiol
  • amanita phalloides
  • tacrine
  • iron overload.

The exact mechanism of action has not been fully elucidated; however, several observations have been made.

Toxin blockade

Silymarin and silybin alter the structure of hepatocyte cell membranes by being incorporated into the hydrophobic-hydrophilic interface of the microsomal bilayer. Additionally, inhibition of cyclic AMP-dependent phosphodiesterase by silybin has been shown in vitro, which results in increased cAMP and stabilisation of lysosomal membranes. Both actions alter cell membrane function and may be important for protecting the cell from toxin-induced damage. Alternatively, components in St Mary’s thistle may bind to the hepatocyte cell membrane receptor site and inhibit binding of toxins to these sites.

Antioxidant activity

Both a direct and an indirect free radical scavenging activity has been observed, with silymarin shown to increase the redox state and total glutathione content of the liver, intestine and stomach in vivo. As such, enhanced antioxidant activity further adds to the herb’s hepatoprotective effects, particularly when hepatic injury involves free radical molecules.

Chelates iron

Hepatic iron toxicity and fibrosis due to iron overload is mediated by lipid peroxidation of biological membranes and the associated organelles. Both silymarin and silybin demonstrate protective effects against hepatic iron toxicity in vivo, primarily owing to antioxidant mechanisms. However, there is some evidence that iron chelation may also be involved.


Silymarin accelerates the regeneration of hepatocytes after liver damage, according to an in vivo study. Silymarin was shown to increase hepatocyte protein synthesis by stimulating the activity of ribosomal RNA polymerase.


St Mary’s thistle extract produces a dose-dependent anti-ulcerogenic activity against indomethacin-induced ulcers, which can be histologically confirmed, according to research with test animals. This is associated with reduced acid output, increased mucin secretion, increased PGE2 release and decreased leukotriene release.

Experiments with the silymarin constituent group have found it to be effective in the prevention of gastric ulceration induced by cold-restraint stress in rats (Alarcon et al 1992) and post-ischaemic gastric mucosal injury.


The anti-inflammatory activity of silymarin is due to several different mechanisms, such as antioxidant and membrane-stabilising effects, and inhibition of the production or release of inflammatory mediators, such as arachidonic acid metabolites. Inhibitory activity on lipo-oxygenase, COX and PG synthetase has been demonstrated in several in vitro assays and animal studies.


In vitro experiments with kidney cells damaged by paracetamol, cisplatin orvincristin demonstrate that administration of silybin before or after the chemical-induced injury can lessen or avoid the nephrotoxic effects. Animal studies have confirmed the nephroprotective effect for cisplatin-induced injury. In one study, the effects of cisplatin on glomerular and proximal tubular function as well as proximal tubular morphology were totally or partly ameliorated by silybin.


Silybin has shown mast-cell-stabilisation activity in vivo, which was confirmed some years later and found to be dose-dependent. More recently, silymarin has been shown to exert protective effects in the early phase of asthma, most likely due to its influence on histamine release.


Silymarin reduces markers for collagen accumulation in the liver and exerts antifibrotic activity, according to an animal model of liver fibrosis.


In a variety of experimental tumour models and cell systems, silymarin and silybin have been found to have both cancer preventive and anticancer activity.

In vitro studies have shown that silymarin possesses exceptionally high cancer-preventive effects in different mouse skin carcinogenesis models and affords strong anticancer effects in human skin, cervical, prostate, bladder and breast carcinoma cells. Recent investigation has also identified that silibinin is biologically active against hepatocellular carcinoma cells.

Two studies involving the use of topical silymarin in hairless mice before chemical carcinogenesis and photocarcinogenesis have shown a protective effect that resulted in a statistically significant decrease in tumour incidence, tumour multiplicity, and tumour volume per mouse in the treated groups. Furthermore, this chemopreventive effect was found to be dose-dependent in one of the studies, in which the topical application ranged from 3 to 12 mg per mouse, with the 12-mg application conferring the most protection.

It appears that several mechanisms are responsible, besides an antioxidant effect. Anti-angiogenic activity has been observed in vitro, and is likely to be involved. Additionally, in vivo research has demonstrated chemopreventive effects for silymarin, by inhibiting endogenous tumour promoter TNF-alpha. In regard to skin cancer, silymarin provides substantial protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties and a selective action on NF-kappa-B activation.

St Mary’s thistle:  Other Actions


Cholesterol reduction has been demonstrated for silymarin in two studies of rats fed a high cholesterol diet. Although the mechanism of action is unknown, it has been suggested that inhibition of HMG-CoA reductase is involved and inhibition of cholesterol absorption from dietary sources.

Considering that the herb also contains phytosterols, these too may play a role in cholesterol reduction.


Silymarin demonstrated neuroprotective activity according to preliminary research. A study by Wang et al (2002) demonstrated that silymarin could effectively protect dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting activation of the microglia that represent resident macrophage-like population of brain cells acting in host defence and tissue repair in the CNS. Silymarin induced an increase of reduced glutathione and ascorbic acid levels and superoxide dismutase activity in the brain of treated rats (200 mg/kg/day PO) for 3 days, showing a protective effect on antioxidant defence systems.


Conflicting results from different studies make it difficult to determine what effect silymarin has on liver enzymes. However, there is some in vitro evidence of CYP3A4 inhibition and, possibly, inhibition of other CYP enzymes. At the time of writing, no clinical studies were available to determine the significance of this.

Results published in 2002 suggest that the flavolignans silybin, silydianin and silycristin display a dose-dependent inhibition of CYP3A4, CYP2E1 and CYP2D6. Two other in vitro studies could not confirm inhibitory effects for silymarin on CYP2E1, with one study actually reporting induction activity. In regard to CYP2C9, one early clinical study showed that a daily dose of 210 mg silymarin over 28 days had no influence on the metabolism phenylbutazone.

In 2003, a crossover study of healthy volunteers found that silymarin (160 mg three times daily) had no apparent effect on indinavir plasma concentrations, suggesting no significant effect on CYP3A4 in humans. More recently, a clinical study found no evidence of an interaction between St Mary’s thistle and indinavir when administered in commonly used therapeutic doses.


An in vitro study identified that silymarin inhibited P-glycoprotein (P-gp) ATPase activity in such a way as to suggest direct interaction with P-gp substrate binding.