Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products

Appiah–Opong, Regina; Commandeur, Jan N. M.; Vugt-Lussenburg, Barbara van; Vermeulen, Nico

doi:10.1016/j.tox.2007.03.007

Cited by 155 publications

(106 citation statements)

References 31 publications

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“…Bull. to reduce the CYP1A2 activity in human tissue. [14][15][16] However, the results of the caffeine test in the present study showed that the 90% CI ranges of the phenotypic indices of CYP1A2, NAT2 and XO were within the bioequivalence range defined by the Food and Drug Administration (FDA) ( Table 1 and Fig. 1).…”

Section: Discussionmentioning

confidence: 45%

“…[14][15][16][17][18][19] Safrole, isosafrole and liquiritigenin (essential constituents of Japanese Angelica root or Glycyrrhiza, which are components of YKS) have been shown Biol. Pharm.…”

Section: Discussionmentioning

confidence: 99%

“…YKS consists of seven herbs, i.e., Atractylodes lancea rhizome, Poria sclerotium, Cnidium rhizome, Uncaria hook, Japanese Angelica root, Bupleurum root and Glycyrrhiza. 10) Several of the components of YKS have been reported to be associated with the activity of drug-metabolizing enzymes in vitro, including CYP2D6, CYP3A and/or CYP1A2 [14][15][16][17][18][19] (see Supple-mentary Table 1). For example, Angelica root, Glycyrrhiza root and Cnidium rhizome have been shown to inhibit the activity of CYP3A4 in vitro.…”

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confidence: 99%

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The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers

Soraoka

Oniki

Matsuda

et al. 2016

Biological & Pharmaceutical Bulletin

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The concomitant use of herb and prescription medications is increasing globally. Herb-drug interactions are therefore a clinically important problem. Yokukansan (YKS), a Japanese traditional herbal medicine, is one of the most frequently used herbal medicines. It is effective for treating the behavioral and psychological symptoms of dementia. We investigated the potential effects of YKS on drug-metabolizing enzyme activities in humans. An open-label repeat-dose study was conducted in 26 healthy Japanese male volunteers (age: 22.7 2.3 years) with no history of smoking. An 8-h urine sample was collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan before and after the administration of YKS (2.5 g, twice a day for 1 week). The activities of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) were assessed based on the urinary metabolic indices of caffeine and dextromethorphan, and the urinary excretion ratio of 6β-hydroxycortisol to cortisol. There were no statistically significant differences in the activities of the examined enzymes before or after the 7-d administration of YKS. Although further studies assessing the influence of YKS on the pharmacokinetics and pharmacodynamics of the substrates of the drug-metabolizing enzymes are needed to verify the present results, YKS is unlikely that a pharmacokinetic interaction will occur with concomitantly administered medications that are predominantly metabolized by the CYP1A2, CYP2D6, CYP3A, XO and NAT2.Key words yokukansan (YKS); herb-drug interaction; drug-metabolizing enzyme; Kampo Dementia is a progressive, irreversible illness and is a worldwide health priority that is associated with an increasing public health burden. 1,2) Alzheimer's disease, a neurodegenerative brain disorder, is the most common form of dementia.

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Section: Discussionmentioning

confidence: 45%

“…[14][15][16][17][18][19] Safrole, isosafrole and liquiritigenin (essential constituents of Japanese Angelica root or Glycyrrhiza, which are components of YKS) have been shown Biol. Pharm.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers

Soraoka

Oniki

Matsuda

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Inhibition of BFCOD BFCOD activity is used as a marker of CYP3A in humans (Renwick et al, 2000;Appiah-Opong et al, 2007) and pigs (Nannelli et al, 2008), although some studies have used BFC as a marker of CYP1A/2B in humans and rats (Price et al, 2008). In fish, BFC is believed to be the specific substrate for CYP3A (Christen et al, 2009).…”

Section: Inhibition Patternmentioning

confidence: 99%

Comparison of three fluorescent CYP3A substrates in two vertebrate models: pig and Atlantic salmon

Žlábek¹,

Zamaratskaia²

2012

Animal

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We investigated in vitro inhibitory effects of ketoconazole (KTZ) on cytochrome P450 activity in microsomes from pigs and Atlantic salmon. The following enzymatic reactions were studied: 7-benzyloxyresorufin and 7-ethoxyresorufin O-dealkylation (BROD and EROD, respectively), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD) and 7-benzyloxyquinoline O-debenzylation (BQOD). KTZ was a potent non-competitive inhibitor of BROD and BQOD in the microsomes from pigs, whereas in the microsomes from Atlantic salmon, these reactions were competitively inhibited by KTZ. BFCOD activity was inhibited by KTZ in a non-competitive manner in both species. KTZ non-competitively inhibited EROD in Atlantic salmon, but not in porcine microsomes. The activity of BROD and BQOD was higher in male than that in female pigs, but the activity of BFCOD showed no sex-related differences.

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“…4,5 The use of this kind of molecules with differential specificities and the effect of these molecules on directed enzymatic reactions has been a useful tool to identify enzymes related with the biotransformation of certain xenobiotics, endogenous metabolites and drugs. [6][7][8][9] A widely used strategy to identify an enzyme involved in a metabolic pathway is to correlate the prototype enzymatic activity with the target substrate molecule activity. [10][11][12][13] In the same way, quantification of enzyme expression by immunoblot and correlation of the amount of protein expressed with the enzyme activity of interest has been used to characterize enzymatic activities.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic activity in turkey, duck, quail and chicken liver microsomes against four human cytochrome P450 prototype substrates and aflatoxin B1

2011

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Cytochrome P450 enzymes (CYP) are a group of monooxygenases able to biotransform several kinds of xenobiotics including aflatoxin B1 (AFB1), a highly toxic mycotoxin. These enzymes have been widely studied in humans and others mammals, but there is not enough information in commercial poultry species about their biochemical characteristics or substrate specificity. The aim of the present study was to identify CYPs from avian liver microsomes with the use of prototype substrates specific for human CYP enzymes and AFB1. Biochemical characterization was carried out in vitro and biotransformation products were detected by high-performance liquid chromatography (HPLC). Enzymatic constants were calculated and comparisons between turkey, duck, quail and chicken activities were done. The results demonstrate the presence of four avian ortholog enzyme activities possibly related with a CYP1A1, CYP1A2, CYP2A6 (activity not previously identified) and CYP3A4 poultry orthologs, respectively. Large differences in enzyme kinetics specific for prototype substrates were found among the poultry species studied. Turkey liver microsomes had the highest affinity and catalytic rate for AFB1 whereas chicken enzymes had the lowest affinity and catalytic rate for the same substrate. Quail and duck microsomes showed intermediate values. These results correlate well with the known in vivo sensitivity for AFB1 except for the duck. A high correlation coefficient between 7-ethoxyresorufin-Odeethylase (EROD) and 7-methoxyresorufin-O-deethylase (MROD) activities was found in the four poultry species, suggesting that these two enzymatic activities might be carried out by the same enzyme. The results of the present study indicate that four prototype enzyme activities are present in poultry liver microsomes, possibly related with the presence of three CYP avian orthologs. More studies are needed in order to further characterize these enzymes.

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Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products

Cited by 155 publications

References 31 publications

The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers

The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers

Comparison of three fluorescent CYP3A substrates in two vertebrate models: pig and Atlantic salmon

Enzymatic activity in turkey, duck, quail and chicken liver microsomes against four human cytochrome P450 prototype substrates and aflatoxin B1

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