PT - JOURNAL ARTICLE AU - Raman Venkataramanan AU - Vinod Ramachandran AU - Bernard J. Komoroski AU - Shimin Zhang AU - Paul L. Schiff AU - Stephen C. Strom TI - Milk Thistle, a Herbal Supplement, Decreases the Activity of CYP3A4 and Uridine Diphosphoglucuronosyl Transferase in Human Hepatocyte Cultures DP - 2000 Nov 01 TA - Drug Metabolism and Disposition PG - 1270--1273 VI - 28 IP - 11 4099 - http://dmd.aspetjournals.org/content/28/11/1270.short 4100 - http://dmd.aspetjournals.org/content/28/11/1270.full SO - Drug Metab Dispos2000 Nov 01; 28 AB - Milk thistle extract is one of the most commonly used nontraditional therapies, particularly in Germany. Milk thistle is known to contain a number of flavonolignans. We evaluated the effect of silymarin, on the activity of various hepatic drug-metabolizing enzymes in human hepatocyte cultures. Treatment with silymarin (0.1 and 0.25 mM) significantly reduced the activity of CYP3A4 enzyme (by 50 and 100%, respectively) as determined by the formation of 6-β-hydroxy testosterone and the activity of uridine diphosphoglucuronosyl transferase (UGT1A6/9) (by 65 and 100%, respectively) as measured by the formation of 4-methylumbelliferone glucuronide. Silymarin (0.5 mM) also significantly decreased mitochondrial respiration as determined by MTT reduction in human hepatocytes. These observations point to the potential of silymarin to impair hepatic metabolism of certain coadministered drugs in humans. Indiscriminate use of herbal products may lead to altered pharmacokinetics of certain drugs and may result in increased toxicity of certain drugs. The American Society for Pharmacology and Experimental Therapeutics