Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions

Understanding the potential for adverse drug reactions (ADRs), from herb-drug interactions, is a key aspect of medicinal plant safety, with particular relevance for public health in countries where medicinal plant use is highly prevalent. We undertook an in-depth assessment of extracts of Hyptis ver...

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Main Authors: David Picking, Bentley Chambers, James Barker, Iltaf Shah, Roy Porter, Declan P Naughton, Rupika Delgoda
Format: Article
Language:English
Published: MDPI AG 2018-02-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/23/2/430
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author David Picking
Bentley Chambers
James Barker
Iltaf Shah
Roy Porter
Declan P Naughton
Rupika Delgoda
author_facet David Picking
Bentley Chambers
James Barker
Iltaf Shah
Roy Porter
Declan P Naughton
Rupika Delgoda
author_sort David Picking
collection DOAJ
description Understanding the potential for adverse drug reactions (ADRs), from herb-drug interactions, is a key aspect of medicinal plant safety, with particular relevance for public health in countries where medicinal plant use is highly prevalent. We undertook an in-depth assessment of extracts of Hyptis verticillata Jacq., via its impact on activities of key cytochrome P450 (CYP) enzymes (CYPs 1A1, 1A2, 1B1, 3A4 and 2D6), its antioxidant properties (determined by DPPH assays) and chemical characterisation (using LC-MS). The dried plant aqueous extract demonstrated potent inhibition of the activities of CYPs 1A1 (7.6 µg/mL), 1A2 (1.9 µg/mL), 1B1 (9.4 µg/mL) and 3A4 (6.8 µg/mL). Further analysis of other crude extracts demonstrated potent inhibition of CYP1A2 activity for a dried plant ethanol extract (1.5 µg/mL), fresh plant ethanol extract (3.9 µg/mL), and moderate activity for a fresh plant aqueous extract (27.8 µg/mL). All four extracts demonstrated strong antioxidant activity, compared to the positive control (ascorbic acid, 1.3 µg/mL), with the dried plant ethanol extract being the most potent (1.6 µg/mL). Analysis of the dried plant aqueous extract confirmed the identity of seven phytochemicals, five lignans and two triterpenes. Individual screening of these phytochemicals against the activity of CYP1A2 identified yatein as a moderate inhibitor (71.9 μM), likely to contribute to the plant extract’s potent bioactivity. Further analysis on the impact of this plant on key drug metabolizing enzymes in vivo appears warranted for likely ADRs, as well as furthering development as a potential chemopreventive agent.
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spelling doaj.art-63f04080adbc4ab1b0bd6882a56554172022-12-21T19:13:22ZengMDPI AGMolecules1420-30492018-02-0123243010.3390/molecules23020430molecules23020430Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug InteractionsDavid Picking0Bentley Chambers1James Barker2Iltaf Shah3Roy Porter4Declan P Naughton5Rupika Delgoda6Natural Products Institute, University of the West Indies, Mona, Kingston 7, JamaicaTropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, JamaicaSchool of Life Sciences, Pharmacy & Chemistry, Kingston University, Kingston upon Thames, UKCollege of Science, United Arab Emirates University, Al-Ain 009713, United Arab EmiratesDepartment of Chemistry, University of the West Indies, Mona, Kingston 7, JamaicaSchool of Life Sciences, Pharmacy & Chemistry, Kingston University, Kingston upon Thames, UKNatural Products Institute, University of the West Indies, Mona, Kingston 7, JamaicaUnderstanding the potential for adverse drug reactions (ADRs), from herb-drug interactions, is a key aspect of medicinal plant safety, with particular relevance for public health in countries where medicinal plant use is highly prevalent. We undertook an in-depth assessment of extracts of Hyptis verticillata Jacq., via its impact on activities of key cytochrome P450 (CYP) enzymes (CYPs 1A1, 1A2, 1B1, 3A4 and 2D6), its antioxidant properties (determined by DPPH assays) and chemical characterisation (using LC-MS). The dried plant aqueous extract demonstrated potent inhibition of the activities of CYPs 1A1 (7.6 µg/mL), 1A2 (1.9 µg/mL), 1B1 (9.4 µg/mL) and 3A4 (6.8 µg/mL). Further analysis of other crude extracts demonstrated potent inhibition of CYP1A2 activity for a dried plant ethanol extract (1.5 µg/mL), fresh plant ethanol extract (3.9 µg/mL), and moderate activity for a fresh plant aqueous extract (27.8 µg/mL). All four extracts demonstrated strong antioxidant activity, compared to the positive control (ascorbic acid, 1.3 µg/mL), with the dried plant ethanol extract being the most potent (1.6 µg/mL). Analysis of the dried plant aqueous extract confirmed the identity of seven phytochemicals, five lignans and two triterpenes. Individual screening of these phytochemicals against the activity of CYP1A2 identified yatein as a moderate inhibitor (71.9 μM), likely to contribute to the plant extract’s potent bioactivity. Further analysis on the impact of this plant on key drug metabolizing enzymes in vivo appears warranted for likely ADRs, as well as furthering development as a potential chemopreventive agent.http://www.mdpi.com/1420-3049/23/2/430cytochrome P450Hyptis verticillata Jacq.enzyme inhibitionherb-drug interactiondrug-herb interactionadverse drug reactionADRchemopreventionantioxidant
spellingShingle David Picking
Bentley Chambers
James Barker
Iltaf Shah
Roy Porter
Declan P Naughton
Rupika Delgoda
Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions
Molecules
cytochrome P450
Hyptis verticillata Jacq.
enzyme inhibition
herb-drug interaction
drug-herb interaction
adverse drug reaction
ADR
chemoprevention
antioxidant
title Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions
title_full Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions
title_fullStr Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions
title_full_unstemmed Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions
title_short Inhibition of Cytochrome P450 Activities by Extracts of Hyptis verticillata Jacq.: Assessment for Potential HERB-Drug Interactions
title_sort inhibition of cytochrome p450 activities by extracts of hyptis verticillata jacq assessment for potential herb drug interactions
topic cytochrome P450
Hyptis verticillata Jacq.
enzyme inhibition
herb-drug interaction
drug-herb interaction
adverse drug reaction
ADR
chemoprevention
antioxidant
url http://www.mdpi.com/1420-3049/23/2/430
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