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Evidence-Based Complementary and Alternative Medicine
Volume 2011 (2011), Article ID 913898, 9 pages
http://dx.doi.org/10.1093/ecam/nep229
Original Article

Curdione Plays an Important Role in the Inhibitory Effect of Curcuma aromatica on CYP3A4 in Caco-2 Cells

1Department of Pharmaceutics, School of Pharmaceutical Sciences, Mukogawa Women's University, 9-11-68 koushien, Nishinomiya City, Hyogo, Japan
2Division of Pharmacognosy, Department of Medicinal Resources, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama City, Toyama, Japan
3Department of Medicinal Resources, Graduate School of Pharmaceutical Science, Osaka University, 1-6 Yamadaoka, Suita City, Osaka, Japan

Received 6 April 2009; Accepted 1 December 2009

Copyright © 2011 Xiao-Long Hou et al. 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.

Abstract

Curcuma aromatica is a plant belonging to genus Curcuma of family Zingiberaceae and is widely used as supplements in Japan. Rhizomes of C. aromatica have curcumin as a major yellow pigment and curdione as a main ingredient of essential oils. In this study, we investigated the affect of C. aromatica on CYP3A4 using 1α,25-(OH)2-D3-treated Caco-2 clone cells. Caco-2 cells were treated with methanol extract (0.1 mg ml−1), its hexane soluble fraction (0.1 mg ml−1), curcumin (4 μM) and curdione (20 μM) for 72 hours. Nifedipine was used as a substrate of CYP3A4. Methanol extract, hexane fraction and curdione inhibited the formation of oxidized nifedipine by 50–70%, and curcumin showed no effect. The IC50s of methanol extract, hexane fraction and curdione to oxidized nifedipine formation were 21, 14 and 3.9 μg ml−1 (16.9 μM), respectively. The content of curdione in methanol extract was 11.4%. Moreover, all of methanol extract, hexane fraction and curdione decreased CYP3A4 protein expression but had no affect on CYP3A4 mRNA expression. Our results showed that these drugs further decreased the CYP3A4 protein expression level after the protein synthesis was inhibited by cychroheximide. These findings suggest that curdione plays an important role in the CYP3A4 inhibitory activity of C. aromatica and curdione might inhibit the activity by accelerating the degradation of CYP3A4.