title: Inhibitory effects of curcumin on activity of cytochrome P450 2C9 enzyme in human and 2C11 in rat liver microsomes.
abstract: Cytochrome P450 2C9 (CYP2C9), one of the most important phase I drug metabolizing enzymes, could catalyze the reactions that convert diclofenanc into diclofenac 4'-hydroxylation. Evaluation of the inhibitory effects of compounds on CYP2C9 is clinically important because inhibition of CYP2C9 could result in serious drug-drug interactions. The objective of this work was to investigate the effects of curcumin on CYP2C9 in human and cytochrome P450 2C11 (CYP2C11) in rat liver microsomes. The results showed that curcumin inhibited CYP2C9 activity (10 µmol L(-1) diclofenac) with half-maximal inhibition or a half-maximal inhibitory concentration (IC50) of 15.25 µmol L(-1) and Ki = 4.473 µmol L(-1) in human liver microsomes. Curcumin's mode of action on CYP2C9 activity was noncompetitive for the substrate diclofenanc and uncompetitive for the cofactor NADPH. In contrast to its potent inhibition of CYP2C9 in human, diclofenanc had lesser effects on CYP2C11 in rat, with an IC50 ≥100 µmol L(-1). The observations imply that curcumin has the inhibitory effects on CYP2C9 activity in human. These in vitro findings suggest that more attention should be paid to special clinical caution when intake of curcumin combined with other drugs in treatment.
authors: Department of Pharmacology, The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou, Zhejiang , PR China and.
authors: Zhe
authors: Z
authors: Wang
authors: Wei
authors: W
authors: Sun
authors: Cheng-Ke
authors: CK
authors: Huang
authors: Li
authors: L
authors: Wang
authors: Meng-Ming
authors: MM
authors: Xia
authors: Xiao
authors: X
authors: Cui
authors: Guo-Xin
authors: GX
authors: Hu
authors: Zeng-Shou
authors: ZS
authors: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000378:metabolism; D000975:Antioxidants / Q000009:adverse effects / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003474:Curcumin / Q000009:adverse effects* / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9 / Q000737:chemistry / Q000378:metabolism*; D065688:Cytochrome P-450 CYP2C9 Inhibitors / Q000009:adverse effects / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000009:adverse effects* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004008:Diclofenac / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects*; D018565:Food-Drug Interactions; D006801:Humans; D007700:Kinetics; D008297:Male; D050216:Metabolic Detoxication, Phase I; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D039181:Steroid 16-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D065688:Cytochrome P-450 CYP2C9 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004008:Diclofenac; D009249:NADP; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D003474:Curcumin
keywords: CYP2C9; Curcumin; diclofenac 4′-hydroxylation; diclofenanc; liver microsomes