Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6 |
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| Institution: | 1. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, South Korea;2. College of Agriculture and Life Sciences, Kyungpook National University, Daegu 702-701, South Korea;3. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea;1. Department of Transplantation and Vascular Surgery, Korea University College of Medicine, Seoul, Korea;2. Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea;3. Department of Surgery, Mongolian National University of Medical Science, Ulan Bator, Mongolia;4. Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea;1. Animal Biotechnology, Graduate School of Bio and Information Technology, Institute of Genetic Engineering, Hankyong National University, Ansung 456-749, Republic of Korea;2. Department of Food and Nutrition, Hoseo University, Asan 336-795, Republic of Korea;1. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;2. Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;1. Department of Rehabilitation Medicine of Korean Medicine, Chungju Hospital of Korean Medicine, College of Korean Medicine, Semyung University, Jecheon 27429, Republic of Korea;2. Development of Periodontics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;1. Dongguan Scientific Research Center, Guangong Medical University, Dongguan, Guangdong, 523-808, China;2. School of Pharmacy, Guangdong Medical University, Dongguan 523-808, China;3. State key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China |
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| Abstract: | Hyperoside, quercetin-3-O-galactoside, is a flavonoid isolated from Oenanthe javanica. In the present study, we investigated potential herb-drug inhibitory effects of hyperoside on nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) and human recombinant cDNA expressed CYP using a cocktail probe assay. Hyperoside strongly inhibited CYP2D6-catalyzed dextromethorphan O-demethylation, with IC50 values of 1.2 and 0.81 μM after 0 and 15 min of preincubation, and a Ki value of 2.01 μM in HLMs, respectively. Hyperoside strongly decreased CYP2D6 activity dose-, but not time-, dependently in HLMs. In addition, the Lineweaver–Burk and Secondary plots for the inhibition of CYP2D6 in HLMs fitted a competitive inhibition mode. Furthermore, hyperoside decreased CYP2D6-catalyzed dextromethorphan O-demethylation activity of human recombinant cDNA-expressed CYP2D6, with an IC50 value of 3.87 μM. However, other CYPs were not inhibited significantly by hyperoside. In conclusion, our data demonstrate that hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and suggest that hyperoside might cause herb-drug interactions when co-administrated with CYP2D substrates. |
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| Keywords: | Hyperoside Human liver microsomes CYP2D6 Inhibitor Herb–drug interaction |
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