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

Drug Metab Pers Ther. 2017 Dec 20;32(4):201-208. doi: 10.1515/dmpt-2017-0020.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Allophylus cominia; P-glycoprotein; cytochrome P450; drug-transporters; metabolising systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / drug effects
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytochrome P-450 Enzyme System / drug effects*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Female
  • Herb-Drug Interactions*
  • Male
  • Mice
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Rats
  • Sapindaceae / chemistry*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Plant Extracts
  • Doxorubicin
  • Cytochrome P-450 Enzyme System