Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor
Language: 
English
Abstract: 

Curcuminoid extract and piperine are being evaluated for beneficial effects in Alzheimer's disease, among other intractable disorders. Consequently, we studied the potential for herb-drug interactions involving cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes. The curcuminoid extract inhibited SULT > CYP2C19 > CYP2B6 > UGT > CYP2C9 > CYP3A activities with IC(50) values ranging from 0.99 +/- 0.04 to 25.3 +/- 1.3 microM, whereas CYP2D6, CYP1A2, and CYP2E1 activities were less affected (IC(50) values > 60 microM). Inhibition of CYP3A activity by curcuminoid extract was consistent with competitive inhibition (K(i) = 11.0 +/- 1.3 microM), whereas inhibition of both CYP2C9 and CYP2C19 activities were consistent with mixed competitive-noncompetitive inhibition (10.6 +/- 1.1 and 7.8 +/- 0.9 microM, respectively). Piperine was a relatively selective noncompetitive inhibitor of CYP3A (IC(50) 5.5 +/- 0.7 microM, K(i) = 5.4 +/- 0.3 microM) with less effect on other enzymes evaluated (IC(50) > 29 microM). Curcuminoid extract and piperine inhibited recombinant CYP3A4 much more potently (by >5-fold) than CYP3A5. Pure synthetic curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) were also evaluated for their effects on CYP3A, CYP2C9, UGT, and SULT activities. All three curcuminoids had similar effects on CYP3A, UGT, and SULT activity, but demethoxycurcumin (IC(50) = 8.8 +/- 1.2 microM) was more active against CYP2C9 than either curcumin or bisdemethoxycurcumin (IC(50) > 50 microM). Based on these data and expected tissue concentrations of inhibitors, we predict that a p.o. administered curcuminoid/piperine combination is most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the intestinal mucosa.

Author(s): 
Volak, Laurie P.
Ghirmai, Senait
Cashman, John R.
Court, Michael H.
Item Type: 
Journal Article
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals
Journal Abbreviation: 
Drug Metab. Dispos.
Publication Date: 
Aug 2008
Publication Year: 
2008
Pages: 
1594-1605
Volume: 
36
Issue: 
8
ISSN: 
1521-009X
DOI: 
10.1124/dmd.108.020552
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 18480186 PMCID: PMC2574793

Turabian/Chicago Citation

Laurie P. Volak, Senait Ghirmai, John R. Cashman and Michael H. Court. Aug 2008. "Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor." Drug Metabolism and Disposition: The Biological Fate of Chemicals 36: 8: 1594-1605. 10.1124/dmd.108.020552.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1124/dmd.108.020552 | issn = 1521-009X | volume = 36 | pages = 1594-1605 | last = Volak | first = Laurie P. | coauthors = Ghirmai, Senait, Cashman, John R., Court, Michael H. | title = Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor | journal = Drug Metabolism and Disposition: The Biological Fate of Chemicals | date = Aug 2008 | pmid = | pmc = }} </ref>