Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis

We studied the effects of schisandrol A (SCH) and gomisin A (GUM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GUM inhibited CYP3A4 activity with IC50 values of 32.02 mu M and 1.39 mu M, respectively. SCH or GUM at concentrations up to 100 mu M did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GUM could affect cellular drug metabolism in addition to drug uptake. (C) 2009 Elsevier GmbH. All rights reserved.