Abstract
Mangosteen is a xanthone-containing fruit found in Southeast Asia for which 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 (P450) enzymes responsible for the metabolism of its individual components. The various xanthone derivatives were found to be both substrates and inhibitors for multiple P450 isoforms. Aqueous extracts of the mangosteen pericarp were analyzed for xanthone content as well as inhibition potency. Finally, in vivo plasma concentrations of α-mangostin, the most abundant xanthone derivative found in mangosteen, were predicted using Simcyp and found to be well above their respective in vitro Ki values for CYP2C8 and CYP2C9.
Footnotes
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.109.028043.
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ABBREVIATIONS: P450, cytochrome P450; LC, liquid chromatography; MS/MS, tandem mass spectrometry; HPLC, high-performance liquid chromatography; MRM, multiple reaction monitoring; AUC, area under the curve; FDA, U.S. Food and Drug Administration.
- Accepted June 11, 2009.
- Received April 15, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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