Abstract − Analytical Sciences, 28(12), 1197 (2012).
High-throughput Screening of Inhibitory Effects of Bo-yang-hwan-o-tang on Human Cytochrome P450 Isoforms in vitro Using UPLC/MS/MS
AUTH: Miran LEE,*1,*2,*3 Jeonghyeon PARK,*2,*3,*4 Mi-sun LIM,*2 Sook Jin SEONG,*2,*3,*4 Joomi LEE,*2,*3,*4 Jeong Ju SEO,*2,*3,*4 Yong-Ki PARK,*5 Hae Won LEE,*2 and Young-Ran YOON*1,*2,*3
AFFL: *1 Department of Molecular Medicine, Kyungpook National University School of Medicine, 101 Dongin2ga, Junggu, Daegu 700-412, South Korea
*2 Clinical Trial Center, Kyungpook National University Hospital, 130 Dongduk-ro, Junggu, Daegu 700-721, South Korea
*3 BK21 Program, Kyungpook National University School of Medicine, 101 Dongin2ga, Junggu, Daegu 700-412, South Korea
*4 Department of Biomedical Science, Kyungpook National University Graduate School, 101 Dongin2ga, Junggu, Daegu 700-412, South Korea
*5 Department of Herbology, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, South Korea ABST: Bo-yang-hwan-o-tang (BHT) is an oriental herbal medicine for treating brain disorders such as cerebral ischemia. The objective of this study was to develop an economically feasible and time-saving high-throughput screening method to monitor the potential inhibitory effects of BHT on human cytochrome P450 (CYP) enzymes in vitro. Two cocktail sets were used for incubation of human liver microsomes: Cocktail A: 6 probe substrates for CYP1A2, CYP2A6, CYP2C8, CYP2C19, CYP2D6, CYP3A4; Cocktail B: 3 for CYP2B6, CYP2C9, CYP2E1. The concentrations of the substrate metabolites were simultaneously analyzed using UPLC/MS/MS. The BHT extract had almost negligible inhibitory effects on the nine human CYP isoforms tested, with the half-maximal inhibitory concentration value ranged from 3624.99 to 45412.44 μg/ml. The results suggest that BHT extract has no inhibitory effects on CYP isoforms within the clinically recommended dosage range. We conclude that BHT might be free of drug-herb interactions when co-administered with other medicines. However, more in vivo human studies are needed to confirm these results. The high-throughput screening method can be a useful tool for drug discovery and for understanding drug interactions.
*2 Clinical Trial Center, Kyungpook National University Hospital, 130 Dongduk-ro, Junggu, Daegu 700-721, South Korea
*3 BK21 Program, Kyungpook National University School of Medicine, 101 Dongin2ga, Junggu, Daegu 700-412, South Korea
*4 Department of Biomedical Science, Kyungpook National University Graduate School, 101 Dongin2ga, Junggu, Daegu 700-412, South Korea
*5 Department of Herbology, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, South Korea ABST: Bo-yang-hwan-o-tang (BHT) is an oriental herbal medicine for treating brain disorders such as cerebral ischemia. The objective of this study was to develop an economically feasible and time-saving high-throughput screening method to monitor the potential inhibitory effects of BHT on human cytochrome P450 (CYP) enzymes in vitro. Two cocktail sets were used for incubation of human liver microsomes: Cocktail A: 6 probe substrates for CYP1A2, CYP2A6, CYP2C8, CYP2C19, CYP2D6, CYP3A4; Cocktail B: 3 for CYP2B6, CYP2C9, CYP2E1. The concentrations of the substrate metabolites were simultaneously analyzed using UPLC/MS/MS. The BHT extract had almost negligible inhibitory effects on the nine human CYP isoforms tested, with the half-maximal inhibitory concentration value ranged from 3624.99 to 45412.44 μg/ml. The results suggest that BHT extract has no inhibitory effects on CYP isoforms within the clinically recommended dosage range. We conclude that BHT might be free of drug-herb interactions when co-administered with other medicines. However, more in vivo human studies are needed to confirm these results. The high-throughput screening method can be a useful tool for drug discovery and for understanding drug interactions.
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