Received for publication April 16, 2009.
Revised June 10, 2009.
Accepted for publication June 11, 2009.

In Vitro Inhibition of Multiple Cytochrome P450 Isoforms by Xanthone Derivatives from Mangosteen Extract

Abstract

Mangosteen is a xanthone-containing fruit found in Southeast Asia whose health claims include maintaining healthy immune and gastrointestinal systems to slowing the progression of tumor growth and neurodegenerative diseases. Previous studies have identified multiple xanthones in the pericarp of the mangosteen fruit. The aim of the current study was to assess the drug inhibition potential of mangosteen in vitro as well as the cytochrome P450 (CYP) enzymes responsible for the metabolism of its individual components. The various xanthone derivatives were found to be both substrates and inhibitors for multiple CYP isoforms. Aqueous extracts of the mangosteen pericarp were analyzed for xanthone content as well as inhibition potency. Finally, in vivo plasma concentrations of -mangostin, the most abundant xanthone derivative found in mangosteen, were predicted using SimCYP and found to be well above their respective in vitro K_i values for CYP2C8 and CYP2C9.

Key words: CYP inhibition, drug interactions