Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers.
BACKGROUND
Curcumin is a kind of plant polyphenol that is extracted from the rhizome of Curcuma longa. Studies about the effect of curcumin on the activity of drug-metabolizing enzymes in humans are lacking.


OBJECTIVE
To investigate the effect of curcumin on the activities of CYP1A2, CYP2A6, N-acetyltransferase (NAT2), and xanthine oxidase (XO) in vivo, using caffeine as a probe drug.


METHODS
Sixteen unrelated, healthy Chinese men were recruited for the study. There were 2 phases in the study. In the first phase, volunteers orally received 100 mg caffeine and 0- to 12-hour blood and urine samples were collected. In the second phase, volunteers received 1000 mg curcumin once daily for 14 continuous days, and blood and urine samples were collected on day 15, following the same procedure used on the first day. Urinary caffeine metabolite ratios were used as the indicators of the activities of CYP1A2, CYP2A6, NAT2, and XO. The pharmacokinetics of caffeine and its metabolites were determined by high-performance liquid chromatography.


RESULTS
In the curcumin-treated group, CYP1A2 activity was decreased by 28.6% (95% CI 15.6 to 41.8; p < 0.000), while increases were observed in CYP2A6 (by 48.9%; 95% CI 25.3 to 72.4; p < 0.000). Plasma area under the curve from zero to 12 hours of 1,7-dimethylxanthine (17X) was decreased by 27.2% (95% CI 6.1 to 48.3; p = 0.014). The urinary excretion of 17X and 1-methylxanthine was significantly decreased by 36.4% (95% CI 19.4 to 53.6; p < 0.000) and 31.2% (95% CI 8.5 to 54.1; p = 0.010), respectively. The excretion of 1,7-dimethylurate (17U) was significantly increased by 77.3% (95% CI 5.6 to 148.8; p = 0.036). No significant changes were observed for caffeine, 1-methylurate, and 5-acetylamino-6-formylamino-3-methyluracil between the 2 study phases.


CONCLUSIONS
The results indicated that curcumin inhibits CYP1A2 function but enhances CYP2A6 activity. Simultaneously, some pharmacokinetic parameters relating to 17X were affected by curcumin. If this finding is confirmed by other studies, the possibility of herb-drug interactions associated with curcumin should be considered in clinical practice.
Chen
Yao
Y
Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
Liu
Wen-Hui
WH
Chen
Bi-Lian
BL
Fan
Lan
L
Han
Yang
Y
Wang
Guo
G
Hu
Dong-Li
DL
Tan
Zhi-Rong
ZR
Zhou
Gan
G
Cao
Shan
S
Zhou
Hong-Hao
HH
D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000378:metabolism; D044466:Asian People; D002110:Caffeine / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003474:Curcumin / Q000737:chemistry / Q000493:pharmacokinetics*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065637:Cytochrome P-450 CYP2A6; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics*; D041743:Herb-Drug Interactions / Q000502:physiology; D006801:Humans; D008297:Male; D010636:Phenols / Q000737:chemistry / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000493:pharmacokinetics; D059808:Polyphenols; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D002110:Caffeine; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C585710:CYP2A6 protein, human; D019388:Cytochrome P-450 CYP1A2; D065637:Cytochrome P-450 CYP2A6; D003474:Curcumin