In vitro inhibition of CYP3A4 by herbal remedies frequently used by cancer patients

Phytother Res. 2009 Jul;23(7):906-12. doi: 10.1002/ptr.2750.


The herbal remedies Natto K2, Agaricus, mistletoe, noni juice, green tea and garlic, frequently used by cancer patients, were investigated for their in vitro inhibition potential of cytochrome P-450 3A4 (CYP3A4) metabolism. To our knowledge, only garlic and green tea had available data on the possible inhibition of CYP3A4 metabolism. Metabolic studies were performed with human c-DNA baculovirus expressed CYP3A4. Testosterone was used as a substrate and ketoconazole as a positive quantitative inhibition control. The formation of 6-beta-OH-testosterone was quantified by a validated HPLC methodology. Green tea was the most potent inhibitor of CYP3A4 metabolism (IC(50): 73 microg/mL), followed by Agaricus, mistletoe and noni juice (1324, 3594, >10 000 microg/mL, respectively). All IC(50) values were high compared with those determined for crude extracts of other herbal remedies. The IC(50)/IC(25) ratios for the inhibiting herbal remedies ranged from 2.15 to 2.67, indicating similar inhibition profiles of the herbal inhibitors of CYP3A4. Garlic and Natto K2 were classified as non-inhibitors. Although Agaricus, noni juice, mistletoe and green tea inhibited CYP3A4 metabolism in vitro, clinically relevant systemic or intestinal interactions with CYP3A4 were considered unlikely, except for a probable inhibition of intestinal CYP3A4 by the green tea product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricus
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors*
  • Enzyme Inhibitors*
  • Herbal Medicine
  • Humans
  • Ketoconazole / pharmacology
  • Plant Extracts / adverse effects*
  • Tea / adverse effects
  • Testosterone / metabolism
  • Viscum album / adverse effects


  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Plant Extracts
  • Tea
  • Testosterone
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Ketoconazole