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Drug Metabolism and Personalized Therapy 2017-12

In vitro modulation of the cytochrome P450 and ABCB1/P-glycoprotein activities of the aqueous extract of Allophylus cominia (L) Sw. leaves.

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Carlos L Pérez
Maria T Donato
Ivones Hernández
Miriam T Paz Lopes
Evangelina Marrero
Jose A Herrera
Maria J Gómez-Lechón
Idania Rodeiro

Keywords

Abstract

The aqueous extract of the Allophylus cominia (L) Sw (Sapindaceae) leaves has shown anti-diabetic, anti-obesity and anti-inflammatory properties. In the Caribbean region, it is typically used for the treatment of type-2 diabetes.

Considering the herb-drug interaction, the aim of this study was to evaluate the potential effects of the A. cominia extract on the cytochrome P450 (CYP) (rat hepatocyte model) and P-glycoprotein (P-gp) (4T1 cell line) systems.

The extract did not decrease the cell viability after being assayed by the MTT test at up to 1500 μg/mL for 72 h. The exposure of the cultured rat hepatocytes to the product (up to 250 μg/mL) for 48 h increased the activities of CYP-1A2, 2C9, and 2E1 by 1.46-, 1.60-, and 1.51-fold, respectively, compared with the controls. The activities of CYP-2B6, 2D6, and 3A4 were not significantly altered, whereas the activity of P-gp decreased by 2- and 4-fold. In addition, the extracts at 100 and 200 μg/mL significantly increased doxorubicin cytotoxicity in these cells 24 h after treatment.

The findings indicate that the A. cominia extract modulates the CYP and P-gp systems increasing sensitivity to doxorubicin. Further studies are necessary to evaluate the potential herb-drug interaction or chemosensitive properties.

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