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Rapid CommunicationShort 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
Drug Metabolism and Disposition November 2000, 28 (11) 1270-1273;
Raman Venkataramanan
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Vinod Ramachandran
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Bernard J. Komoroski
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Shimin Zhang
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Paul L. Schiff
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Stephen C. Strom
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Abstract

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.

Footnotes

  • Send reprint requests to: Raman Venkataramanan, Ph.D., F.C.P., Professor of Pharmaceutical Sciences and Pathology, 718 Salk Hall, University of Pittsburgh, Pittsburgh, PA 15261. E-mail:rv+{at}pitt.edu

  • This work was supported in part by University of Pittsburgh Pharmacy Associates grant from the School of Pharmacy (R.V., B.J.K.), by Pfizer undergraduate summer Research Fellowship (B.J.K.), and by National Institutes of Health N01-DK-9-2310 (S.C.S.).

  • Abbreviations used are::
    UDPGA
    uridine diphosphoglucuronic acid
    UGT
    uridine diphosphoglucuronosyl transferase
    CYP
    cytochrome P450
    4-MU
    4-methylumbelliferone
    4-MUG
    4-methylumbelliferone glucuronide
    MTT
    (3-(4,5-dimethylthiazol-2yl) 2,5-diphenyltetrazolium bromide, Thiazolyl blue
    DMSO
    dimethyl sulfoxide
    OH
    hydroxy
    • Received June 20, 2000.
    • Accepted July 31, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 28 (11)
Drug Metabolism and Disposition
Vol. 28, Issue 11
1 Nov 2000
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Rapid CommunicationShort 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
Drug Metabolism and Disposition November 1, 2000, 28 (11) 1270-1273;

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Rapid CommunicationShort 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
Drug Metabolism and Disposition November 1, 2000, 28 (11) 1270-1273;
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