Milk Thistle (Silybum marianum)
Silybum marianum is a stout annual or biennial plant found in dry rocky soils in southern and western Europe and some parts of the United States. The branched stem grows 1 to 3 ft high and bears alternate dark green, shiny leaves with spiny, scalloped edges that are markedly streaked with white along the veins. The solitary flower heads are reddish purple with bracts ending in sharp spines. Flowering season is from June to August. The seeds, fruit, and leaves are used for medicinal purposes.
Perhaps the most widespread folk use of this plant has been in assisting the nursing mother in the production of milk. It was also used in Germany for curing jaundice and biliary derangements. It is interesting to note that the discovery of the liver-protecting flavanolignans in S. marianum was the result not of systemic pharmacologic screening but rather of investigation of Silybum’s empiric effects in liver disorders.
Silybum’s ability to prevent liver destruction and enhance liver function is due largely to silymarin’s inhibition of the factors responsible for hepatic damag - free radicals and leukotrienes - coupled with its ability to stimulate liver protein synthesis. Silybum components prevent free radical damage by acting as antioxidants. Silymarin is many times more potent in antioxidant activity than vitamin E.
Perhaps the most interesting effect of Silybum components on the liver is their ability to stimulate protein synthesis. This results in an increase in the production of new liver cells to replace the damaged old ones. Researchers have suggested that “silybinin imitates in some way a physiological regulator in animal cells, so that the structure fits into a specific binding site on the polymerase and in such a way causes the observed effects on rRNA synthesis making the drug from Silybum marianum indeed interesting for liver therapy.” Interestingly, silybinin does not have a stimulatory effect on malignant hepatic tissue.
Silymarin has shown significant anticancer effects in both in vivo and in vitro cancer models - including skin, breast, lung, colon, bladder, prostate, and kidney carcinomas— as well as adjunctive actions when combined with standard cancer therapies. Some of the effects noted include that it:
• Prevents the expression of genes and enzymes pivotal in cancer development
• Modulates imbalance between cell survival and apoptosis through interference with the expression of cell cycle regulators and proteins involved in apoptosis
• Exerts significant antimetastatic effects
• Has a synergistic effect when combined with conventional chemotherapy agents, including growth inhibition, reversal of chemoresistance, apoptosis induction, and reduced chemotherapy side effects in a variety of models
These preliminary studies suggest a clinical application in cancer patients as an adjunct to established therapies so as to prevent or reduce chemotherapy as well as radiotherapy-induced toxicity. Considering the significant problem of serious nephrotoxicity (kidney toxicity) from cisplatin and other chemotherapeutic agents, silybinin may be of great value as an adjunct in the treatment of cancer.
Leukotrienes, key chemical mediators of inflammation produced by the transfer of oxygen to polyunsaturated fatty acids (a reaction catalyzed by the enzyme lipoxygenase), can also damage the liver. Silymarin has been shown to be a potent inhibitor of this enzyme, thereby inhibiting the formation of damaging leukotrienes. Silymarin has also been demonstrated to inhibit prostaglandin synthesis during inflammation. Free radical damage to membrane structures due to organic disease or intoxication results in increased release, through lipolysis, of fatty acids. This leads, among other things, to greater prostaglandin and leukotriene synthesis. Silymarin counteracts this deleterious process by suppressing the pathologic decomposition of membrane lipids and inhibiting prostaglandin formation. Leukotrienes and inflammatory prostaglandins are also involved in damage of the liver by toxins, so their neutralization by silybin is another mechanism for its protection of the liver.
The standard dose of milk thistle is based on its silymarin content (70 to 210 mg three times daily). For this reason, standardized extracts are preferred. The best results are achieved at higher dosages - 140 to 210 mg of silymarin three times daily. The dosage for silybin bound to phosphatidylcholine is 120 to 240 mg twice daily. Alcohol-based extracts are virtually always contraindicated in liver disease because a relatively large amount of alcohol is administered to obtain an adequate dose of silymarin in this form.
Silymarin preparations are widely used medications in Europe, where a considerable body of evidence points to very low toxicity. When used at high doses for short periods, silymarin given by various routes to mice, rats, rabbits, and dogs has shown no toxic effects. Studies in rats receiving silymarin for protracted periods have also demonstrated a complete lack of toxicity. Because silymarin possesses choleretic activity, it may produce a looser stool as a result of greater bile flow and secretion. If higher doses are used, it may be appropriate to use bile-sequestering fiber compounds (e.g., guar gum, pectin, psyllium, oat bran) to prevent mucosal irritation and loose stools. Because of silymarin’s lack of toxicity, its long-term use is feasible when necessary.
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