Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents
The co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory e...
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doaj-14392a79f8fb4e97b276b91e6c3ddb0c2020-11-24T21:28:02ZengMDPI AGMolecules1420-30492018-10-012310269610.3390/molecules23102696molecules23102696Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal ConstituentsNurul Huda Abdullah0Sabariah Ismail1Centre for Drug Research, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, MalaysiaCentre for Drug Research, Universiti Sains Malaysia, Gelugor 11800, Pulau Pinang, MalaysiaThe co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory effect of several herbal constituents on one of the most important UGT isoforms, UGT2B7, in human liver microsomes (HLM) and rat liver microsomes (RLM) was investigated. Zidovudine (ZDV) was used as the probe substrate to determine UGT2B7 activity. The intrinsic clearance (Vmax/Km) of ZDV in HLM is 1.65 µL/mg/min which is ten times greater than in RLM, which is 0.16 µL/mg/min. Andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone inhibited ZDV glucuronidation in HLM with IC50 values of 6.18 ± 1.27, 18.56 ± 8.62, 8.11 ± 4.48 and 4.57 ± 0.23 µM, respectively, hence, herb-drug interactions are possible if andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone are taken together with drugs that are highly metabolized by UGT2B7. Meanwhile, only mitragynine and zerumbone inhibited ZDV glucuronidation in RLM with IC50 values of 51.20 ± 5.95 μM and 8.14 ± 2.12 µM, respectively, indicating a difference between the human and rat microsomal model so caution must be exercised when extrapolating inhibitory metabolic data from rats to humans.http://www.mdpi.com/1420-3049/23/10/2696zidovudineUGT2B7andrographolidemitragyninezerumbone |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nurul Huda Abdullah Sabariah Ismail |
spellingShingle |
Nurul Huda Abdullah Sabariah Ismail Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents Molecules zidovudine UGT2B7 andrographolide mitragynine zerumbone |
author_facet |
Nurul Huda Abdullah Sabariah Ismail |
author_sort |
Nurul Huda Abdullah |
title |
Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents |
title_short |
Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents |
title_full |
Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents |
title_fullStr |
Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents |
title_full_unstemmed |
Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents |
title_sort |
inhibition of ugt2b7 enzyme activity in human and rat liver microsomes by herbal constituents |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-10-01 |
description |
The co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory effect of several herbal constituents on one of the most important UGT isoforms, UGT2B7, in human liver microsomes (HLM) and rat liver microsomes (RLM) was investigated. Zidovudine (ZDV) was used as the probe substrate to determine UGT2B7 activity. The intrinsic clearance (Vmax/Km) of ZDV in HLM is 1.65 µL/mg/min which is ten times greater than in RLM, which is 0.16 µL/mg/min. Andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone inhibited ZDV glucuronidation in HLM with IC50 values of 6.18 ± 1.27, 18.56 ± 8.62, 8.11 ± 4.48 and 4.57 ± 0.23 µM, respectively, hence, herb-drug interactions are possible if andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone are taken together with drugs that are highly metabolized by UGT2B7. Meanwhile, only mitragynine and zerumbone inhibited ZDV glucuronidation in RLM with IC50 values of 51.20 ± 5.95 μM and 8.14 ± 2.12 µM, respectively, indicating a difference between the human and rat microsomal model so caution must be exercised when extrapolating inhibitory metabolic data from rats to humans. |
topic |
zidovudine UGT2B7 andrographolide mitragynine zerumbone |
url |
http://www.mdpi.com/1420-3049/23/10/2696 |
work_keys_str_mv |
AT nurulhudaabdullah inhibitionofugt2b7enzymeactivityinhumanandratlivermicrosomesbyherbalconstituents AT sabariahismail inhibitionofugt2b7enzymeactivityinhumanandratlivermicrosomesbyherbalconstituents |
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