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    Milk Thistle (PDQ®): Complementary and alternative medicine - Health Professional Information [NCI] - Laboratory / Animal / Preclinical Studies

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    Silymarin has been shown to stimulate phase II detoxification pathways in mice. Administration of silymarin (100 or 200 mg /kg body weight/day) to SENCAR mice for 3 days significantly increased glutathione S-transferase activity in the liver (P < .01-.001), lung (P < .05-.01), stomach (P < .05), small bowel (P < .01), and skin (P < .01). This effect appeared to be dose-dependent.[34] Administration of silymarin to rats challenged with a toxin (50 mg/kg body weight) resulted in higher levels of glutathione in liver cells, decreased levels of oxidative stress (measured by malondialdehyde concentrations), and less elevated liver function tests (measured by levels of aspartate aminotransferase [AST] and alanine aminotransferase [ALT]).[31] Silymarin and silybin have also been found to accelerate cell regeneration in the liver through stimulation of precursors to DNA synthesis and enhancement of production of the cellular enzymes required for synthesis of DNA.[35,36,37,38,39,40] Laboratory studies have also shown silymarin and silybin to be potent antioxidants.[28,29,41,42,43,44,45,46,47,48] Silymarin has been shown to mitigate oxidative stress in cells treated with pro-oxidant compounds.

    A number of laboratory studies have investigated the effect of silymarin or silybin on the efficacy and toxicity of chemotherapy agents or have measured their direct cytotoxic activity. In an investigation of the effect of a variety of flavonoids on the formation of DNA damage, silymarin did not induce DNA damage in colon (Caco-2) cells, hepatoma (HepG2) cells, and human lymphocytes.[12] At higher concentrations of silymarin (400-1,000 μmol/L) DNA damage was induced in an epithelial cell line (HeLa cells). At higher concentrations (1,000 μmol/L) DNA damage was observed in human lymphocytes. Cell growth was inhibited as the flavonoid concentration was increased in human lymphocytes and HeLa cells. Only at very high concentrations was cell viability affected by silymarin in HepG2 cells. Although this study demonstrated that the flavonolignans of Silybum marianum (L.) are capable of inhibiting cellular proliferation and inducing DNA strand breaks, the results were obtained at very high concentrations that may be difficult to achieve in humans. This study also showed that silymarin does not stimulate cell growth in the HeLa, Burkitt lymphoma, and human hepatoma cell lines.

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