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In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark

Terminalia arjuna Wight and Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Aqueous, hydroalcoholic and alcoholic extract of T. arjuna, arjunic acid and arjungenin were examined for...

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Autores principales: Varghese, Alice, Pandita, Nancy, Gaud, R. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023283/
https://www.ncbi.nlm.nih.gov/pubmed/24843187
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author Varghese, Alice
Pandita, Nancy
Gaud, R. S.
author_facet Varghese, Alice
Pandita, Nancy
Gaud, R. S.
author_sort Varghese, Alice
collection PubMed
description Terminalia arjuna Wight and Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Aqueous, hydroalcoholic and alcoholic extract of T. arjuna, arjunic acid and arjungenin were examined for their potential to inhibit CYP1A enzyme in rat and human liver microsomes. IC(50) values of aqueous, hydroalcoholic and alcoholic extract of T. arjuna was found to be 11.4, 28.9 and 44.6 μg/ml in rat liver microsomes while 30.0, 29.7 and 39.0 μg/ml in human liver microsomes, respectively for CYP1A. However IC(50) values of arjunic acid and arjungenin for both rat liver microsomes and human liver microsomes were found to be >50 μM. Arjunic acid and arjungenin did not show inhibition of CYP1A enzyme up to concentrations of 50 μM. These in vitro data indicate that Terminalia arjuna extracts contain constituents that can potently inhibit the activity of CYP1A, which could in turn lead to undesirable pharmacokinetic drug–herb interactions in vivo. Based on the in vitro data, interaction potential of the aqueous extract of Terminalia arjuna orally in rats was investigated. A probe substrate, phenacetin, was used to index the activity of CYP1A. In vivo pharmacokinetic study of coadministration of aqueous extract of Terminalia arjuna and phenacetin, revealed that the aqueous extract did not lead to any significant change in the pharmacokinetic parameters of phenacetin as compared with control group. Though there was no in vivo–in vitro correlation, drug interactions could arise with drugs having a narrow therapeutic range and extensively cleared by CYP1A enzyme, which could lead to undesirable side effects.
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spelling pubmed-40232832014-05-19 In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark Varghese, Alice Pandita, Nancy Gaud, R. S. Indian J Pharm Sci Research Paper Terminalia arjuna Wight and Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Aqueous, hydroalcoholic and alcoholic extract of T. arjuna, arjunic acid and arjungenin were examined for their potential to inhibit CYP1A enzyme in rat and human liver microsomes. IC(50) values of aqueous, hydroalcoholic and alcoholic extract of T. arjuna was found to be 11.4, 28.9 and 44.6 μg/ml in rat liver microsomes while 30.0, 29.7 and 39.0 μg/ml in human liver microsomes, respectively for CYP1A. However IC(50) values of arjunic acid and arjungenin for both rat liver microsomes and human liver microsomes were found to be >50 μM. Arjunic acid and arjungenin did not show inhibition of CYP1A enzyme up to concentrations of 50 μM. These in vitro data indicate that Terminalia arjuna extracts contain constituents that can potently inhibit the activity of CYP1A, which could in turn lead to undesirable pharmacokinetic drug–herb interactions in vivo. Based on the in vitro data, interaction potential of the aqueous extract of Terminalia arjuna orally in rats was investigated. A probe substrate, phenacetin, was used to index the activity of CYP1A. In vivo pharmacokinetic study of coadministration of aqueous extract of Terminalia arjuna and phenacetin, revealed that the aqueous extract did not lead to any significant change in the pharmacokinetic parameters of phenacetin as compared with control group. Though there was no in vivo–in vitro correlation, drug interactions could arise with drugs having a narrow therapeutic range and extensively cleared by CYP1A enzyme, which could lead to undesirable side effects. Medknow Publications & Media Pvt Ltd 2014 /pmc/articles/PMC4023283/ /pubmed/24843187 Text en Copyright: © Indian Journal of Pharmaceutical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Varghese, Alice
Pandita, Nancy
Gaud, R. S.
In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark
title In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark
title_full In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark
title_fullStr In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark
title_full_unstemmed In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark
title_short In vitro and in vivo Evaluation of CYP1A Interaction Potential of Terminalia Arjuna Bark
title_sort in vitro and in vivo evaluation of cyp1a interaction potential of terminalia arjuna bark
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023283/
https://www.ncbi.nlm.nih.gov/pubmed/24843187
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