Rapid screening of commercially available herbal products for the inhibition of major human hepatic cytochrome P450 enzymes using the N-in-one cocktail.
Self-administration of complementary products concurrently with conventional medication is increasingly common. The potential for cytochrome P450 (CYP) inhibition requires investigation. The N-in-one assay with ten probe substrates for nine CYPs was used with human liver microsomes to investigate ten products. CYP inhibition was measured in a single liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis. Estimated IC(50)-values were determined for the extracts that produced significant inhibition (less than 100 microg ml(-1)). Inhibition of CYP2C19 by dong quai (IC(50) = 13.7-14.3 microg ml(-1) for the methanolic extract) and CYP2D6 by goldenseal (IC(50) = 6.7 and 6.3 microg ml(-1) for the aqueous and methanolic extracts, respectively), are of particular concern as the potential for adverse interactions is high. The inhibition of CYP2C8 by horsetail (IC(50) = 93 microg ml(-1) for the aqueous extract) requires further investigation, as the potential for concurrent use with products that require CYP2C8 for metabolism is significant. CYP3A4 inhibition varied depending on the probe reaction being monitored. The earlier reported findings of inhibition by black cohosh, goldenseal and gotu kola were confirmed. The present work has shown that the N-in-one cocktail is a rapid and reliable method that can be used as an initial screen to help prioritize products that require more detailed investigations and it can also be applied to monitor product variability.
Sevior
D K
DK
RMIT Toxicology, RMIT University, Plenty Road, Bundoora, Victoria 3083, Australia.
Hokkanen
J
J
Tolonen
A
A
Abass
K
K
Tursas
L
L
Pelkonen
O
O
Ahokas
J T
JT
D029971:Angelica sinensis; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D028041:Centella / Q000009:adverse effects / Q000737:chemistry; D031885:Cimicifuga / Q000009:adverse effects / Q000737:chemistry; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020829:Equisetum / Q000009:adverse effects / Q000737:chemistry; D006801:Humans; D039321:Hydrastis / Q000009:adverse effects / Q000737:chemistry; D008658:Inactivation, Metabolic; D000432:Methanol; D008862:Microsomes, Liver / Q000201:enzymology; D010928:Placental Lactogen; D010936:Plant Extracts / Q000494:pharmacology; D028321:Plant Preparations / Q000009:adverse effects / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D014867:Water
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D028321:Plant Preparations; D014867:Water; D010928:Placental Lactogen; C044613:angelicae sinensis extract; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C450259:CYP2C8 protein, human; D065731:Cytochrome P-450 CYP2C19; D065727:Cytochrome P-450 CYP2C8; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000432:Methanol