In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity |
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| Institution: | 1. Aquatic Ecology and Toxicology Group, Center for Organismal Studies (COS), University of Heidelberg, Im Neuenheimer Feld 504, D-69120 Heidelberg, Germany;2. Department of Ecosystem Analysis, Institute for Environmental Research, ABBt - Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany;1. School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China;2. Department of Breast Medicine, Liaoning Cancer Hospital & Institute, Shenyang 110042, China;3. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.;4. Key Laboratory of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou, Liaoning, China.;5. Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, China;6. Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China;7. Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD 20892, USA |
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| Abstract: | This study was designed to investigate eight herbal active constituents (andrographolide, asiaticoside, asiatic acid, madecassic acid, eupatorin, sinensetin, caffeic acid, and rosmarinic acid) on their potential inhibitory effects on human cytochrome P450 1A2 (CYP1A2) activity. A fluorescence-based enzyme assay was performed by co-incubating human cDNA-expressed CYP1A2 with its selective probe substrate, 3-cyano-7-ethoxycoumarin (CEC), in the absence or presence of various concentrations of herbal active constituents. The metabolite (cyano-hydroxycoumarin) formed was subsequently measured in order to obtain IC50 values. The results indicated that only eupatorin and sinensetin moderately inhibited CYP1A2 with IC50 values of 50.8 and 40.2 μM, while the other active compounds did not significantly affect CYP1A2 activity with IC50 values more than 100 μM. Ki values further determined for eupatorin and sinensetin were 46.4 and 35.2 μM, respectively. Our data indicated that most of the investigated herbal constituents have negligible CYP1A2 inhibitory effect. In vivo studies however may be warranted to ascertain the inhibitory effect of eupatorin and sinensetin on CYP1A2 activity in clinical situations |
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| Keywords: | Herbal active constituents CYP1A2 Fluorescence-based enzyme assay Inhibitory effect CEC"} {"#name":"keyword" "$":{"id":"kw0030"} "$$":[{"#name":"text" "_":"3-cyano-7-ethoxycoumarin CYP"} {"#name":"keyword" "$":{"id":"kw0040"} "$$":[{"#name":"text" "_":"cytochrome P450 DMSO"} {"#name":"keyword" "$":{"id":"kw0050"} "$$":[{"#name":"text" "_":"dimethylsulfoxide Michaelis–Menten constant maximum velocity the half maximal (50%) inhibitory concentration the inhibitor concentration required for a half-maximal inhibition NADPH"} {"#name":"keyword" "$":{"id":"kw0100"} "$$":[{"#name":"text" "_":"nicotinamide adenine dinucleotide phosphate |
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