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Sci. Pharm. 2010, 78(3), 473-482; doi:10.3797/scipharm.1002-11

Effects of Garlic on Cytochromes P450 2C9- and 3A4-Mediated Drug Metabolism in Human Hepatocytes

1
University of Washington Department of Pharmaceutics, 1959 Pacific Street, H-272, Box 357610, Seattle, WA 98195, USA
2
University of Washington Department of Pharmacy, 1959 Pacific Street, H H-375, Box 357630, Seattle, WA 98195, USA
3
Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Ave. N. PO Box 19024 Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
Received: 13 February 2010 / Accepted: 9 June 2010 / Published: 9 June 2010
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Abstract

Several reports suggest garlic supplements may inhibit the metabolism of cytochrome P450 (CYP) 2C9 and CYP3A4 substrates, such as warfarin and saquinavir. To characterize the effects of garlic extract on CYP2C9 and CYP3A4 enzyme activity immortalized human hepatocytes (Fa2N-4 cells) were exposed to garlic extract (0–200 μg/mL). CYP2C9 and CYP3A4 enzyme activities were evaluated in parallel with enzymatic activities, expression of respective RNA transcripts was also assessed. Exposure to increasing concentrations of garlic extract led to progressive reduction in Fa2N-4 CYP2C9 activity as detected by diclofenac hydroxylation. CYP2C9 mRNA expression also revealed a concentration-dependent reduction. Greater than 90% reduction in CYP2C9 activity was observed following four days of exposure to 50 μg/mL garlic extract. In contrast, exposure to garlic extract had no effect on the CYP3A4 enzymatic activity or RNA transcript concentration in Fa2N-4. Therefore, suppression of CYP2C9 expression and activity is a heretofore unrecognized mechanism by which garlic extract may modulate CYP activity. Exposure of hepatocytes to garlic extract may reduce the expression and activity of CYP2C9 with no detectible effects on CYP3A4.
Keywords: Garlic; Cytochrome P450 2C9; Drug Interactions Garlic; Cytochrome P450 2C9; Drug Interactions
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

HO, B.E.; SHEN, D.D.; MCCUNE, J.S.; BUI, T.; RISLER, L.; YANG, Z.; HO, R.J.Y. Effects of Garlic on Cytochromes P450 2C9- and 3A4-Mediated Drug Metabolism in Human Hepatocytes. Sci. Pharm. 2010, 78, 473-482.

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