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Vol. 28, Issue 11, 1270-1273, November 2000

SHORT COMMUNICATION
Milk Thistle, a Herbal Supplement, Decreases the Activity of CYP3A4 and Uridine Diphosphoglucuronosyl Transferase in Human Hepatocyte Cultures

Raman Venkataramanan, Vinod Ramachandran, Bernard J. Komoroski, Shimin Zhang, Paul L. Schiff, and Stephen C. Strom

Department of Pharmaceutical Sciences
School of Pharmacy (R.V., V.R., B.J.K., S.Z., P.S.)
Department of Pathology
School of Medicine (R.V., S.C.S.)
University of Pittsburgh
Pittsburgh, Pennsylvania

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-beta -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.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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