In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes
Terminalia arjuna is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Alcoholic and aqueous bark extracts of T. arjuna, arjunic acid, arjunetin and arjungenin were evaluated for their potential to inhibit...
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doaj-07f94206f94143deaf88fd6e2a38e75b2020-11-24T21:54:44ZengElsevierToxicology Reports2214-75002015-01-012C80681610.1016/j.toxrep.2015.02.008In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomesAlice Varghese0Jay Savai1Nancy Pandita2Ram Gaud3Department of Pharmaceutical Chemistry, Shobhaben Pratapbhai Patel, School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, IndiaDepartment of Pharmacology, Shobhaben Pratapbhai Patel, School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, IndiaDepartment of Phytochemistry, School of Science, SVKM's NMIMS, Mumbai, IndiaShobhaben Pratapbhai Patel, School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, IndiaTerminalia arjuna is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Alcoholic and aqueous bark extracts of T. arjuna, arjunic acid, arjunetin and arjungenin were evaluated for their potential to inhibit CYP3A4, CYP2D6 and CYP2C9 enzymes in human liver microsomes. We have demonstrated that alcoholic and aqueous bark extract of T. arjuna showed potent inhibition of all three enzymes in human liver microsomes with IC50 values less than 50 μg/mL. Arjunic acid, arjunetin and arjungenin did not show significant inhibition of CYP enzymes in human liver microsomes. Enzyme kinetics studies suggested that the extracts of arjuna showed reversible non-competitive inhibition of all the three enzymes in human liver microsomes. Our findings suggest strongly that arjuna extracts significantly inhibit the activity of CYP3A4, CYP2D6 and CYP2C9 enzymes, which is likely to cause clinically significant drug–drug interactions mediated via inhibition of the major CYP isozymes.http://www.sciencedirect.com/science/article/pii/S221475001500027XCYP enzymeTerminalia arjunaHuman liver microsomesCYP inhibitionHerb–drug interactionsToxicity |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alice Varghese Jay Savai Nancy Pandita Ram Gaud |
spellingShingle |
Alice Varghese Jay Savai Nancy Pandita Ram Gaud In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes Toxicology Reports CYP enzyme Terminalia arjuna Human liver microsomes CYP inhibition Herb–drug interactions Toxicity |
author_facet |
Alice Varghese Jay Savai Nancy Pandita Ram Gaud |
author_sort |
Alice Varghese |
title |
In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes |
title_short |
In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes |
title_full |
In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes |
title_fullStr |
In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes |
title_full_unstemmed |
In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes |
title_sort |
in vitro modulatory effects of terminalia arjuna, arjunic acid, arjunetin and arjungenin on cyp3a4, cyp2d6 and cyp2c9 enzyme activity in human liver microsomes |
publisher |
Elsevier |
series |
Toxicology Reports |
issn |
2214-7500 |
publishDate |
2015-01-01 |
description |
Terminalia arjuna is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Alcoholic and aqueous bark extracts of T. arjuna, arjunic acid, arjunetin and arjungenin were evaluated for their potential to inhibit CYP3A4, CYP2D6 and CYP2C9 enzymes in human liver microsomes. We have demonstrated that alcoholic and aqueous bark extract of T. arjuna showed potent inhibition of all three enzymes in human liver microsomes with IC50 values less than 50 μg/mL. Arjunic acid, arjunetin and arjungenin did not show significant inhibition of CYP enzymes in human liver microsomes. Enzyme kinetics studies suggested that the extracts of arjuna showed reversible non-competitive inhibition of all the three enzymes in human liver microsomes. Our findings suggest strongly that arjuna extracts significantly inhibit the activity of CYP3A4, CYP2D6 and CYP2C9 enzymes, which is likely to cause clinically significant drug–drug interactions mediated via inhibition of the major CYP isozymes. |
topic |
CYP enzyme Terminalia arjuna Human liver microsomes CYP inhibition Herb–drug interactions Toxicity |
url |
http://www.sciencedirect.com/science/article/pii/S221475001500027X |
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