Toxicology 235 (2007) 83–91 Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products Regina Appiah-Opong, Jan N.M. Commandeur ∗ , Barbara van Vugt-Lussenburg, Nico P.E. Vermeulen Division of Molecular Toxicology, Leiden/Amsterdam Center for Drug Research (LACDR), Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands Received 25 January 2007; received in revised form 7 March 2007; accepted 8 March 2007 Available online 15 March 2007 Abstract Curcumin (diferuloylmethane) is a major yellow pigment and dietary component derived from Curcuma longa. It has potent anti- inflammatory, anticarcinogenic, antioxidant and chemoprotective activities among others. We studied the interactions of curcumin, a mixture of its decomposition products, and four of its individually identified decomposition products (vanillin, vanillic acid, ferulic aldehyde and ferulic acid) on five major human drug-metabolizing cytochrome P450s (CYPs). Curcumin inhibited CYP1A2 (IC 50 , 40.0 M), CYP3A4 (IC 50 , 16.3 M), CYP2D6 (IC 50 , 50.3 M), CYP2C9 (IC 50 , 4.3 M) and CYP2B6 (IC 50 , 24.5 M). Curcumin showed a competitive type of inhibition towards CYP1A2, CYP3A4 and CYP2B6, whereas a non-competitive type of inhibition was observed with respect to CYP2D6 and CYP2C9. The inhibitory activity towards CYP3A4, shown by curcumin may have implications for drug–drug interactions in the intestines, in case of high exposure of the intestines to curcumin upon oral administration. In spite of the significant inhibitory activities shown towards the major CYPs in vitro, it remains to be established, whether curcumin will cause significant drug–drug interactions in the liver, given the reported low systemic exposure of the liver to curcumin. The decomposition products of curcumin showed no significant inhibitory activities towards the CYPs investigated, and therefore, are not likely to cause drug–drug interactions at the level of CYPs. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Cytochrome P450; Curcumin; Drug–food interactions; Enzyme inhibition Abbreviations: CYP, cytochrome P450; HPLC, high performance liquid chromatography; BROD, benzyloxyresorufin O-debenzylase; MROD, methoxyresorufin O-demethylase; DBF, dibenzylfluorescein; BQ, 7-benzyloxyquinoline; BFC, 7-benzyloxy-4-trifluoromethyl- couma-rin; GSH, reduced glutathione; NAC, N-acetyl l-cysteine ∗ Corresponding author. Tel.: +31 205987590; fax: +31 205987610. E-mail address: jnm.commandeur@few.vu.nl (J.N.M. Commandeur). 1. Introduction Multiple drug therapy is a common therapeutic prac- tice especially in patients with multiple complications (Nadler et al., 2003; Hemaiswarya and Doble, 2006). If two or more drugs with affinity for the same cytochrome P450 (CYP) enzyme are co-administered, their biotrans- formation may be compromised, leading to undesirable accumulation of the drugs with toxic side effects as possible consequence. Drug–drug interactions involv- ing CYPs have been identified as an important cause of adverse drug reactions and therapeutic failure (Honig 0300-483X/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2007.03.007