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

• Published in: Phytomedicine (Stuttgart) Vol. 17; no. 8; pp. 702 - 705
• Main Authors: Wan, C.-K., Tse, A.K., Yu, Z.-L., Zhu, G.-Y., Wang, H., Fong, D.W.F.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.07.2010
• Subjects: ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Cyclooctanes - isolation & purification; Cyclooctanes - pharmacology; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P450 3A4; Dioxoles - isolation & purification; Dioxoles - pharmacology; Drug Resistance, Multiple; Fruit; Glutathione; Glutathione - metabolism; Gomisin A; Hep G2 Cells; Herb-Drug Interactions; Humans; Inhibitory Concentration 50; Lignans - isolation & purification; Lignans - pharmacology; Multidrug resistance; Plant Extracts - chemistry; Plant Extracts - pharmacology; Schisandra - chemistry; Schisandra chinensis; Schisandrol A; Schisandrol A; Gomisin A; Schisandra chinensis; Multidrug resistance; Cytochrome P450 3A4; Glutathione
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2009.12.005

We studied the effects of schisandrol A (SCH) and gomisin A (GOM), 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 GOM inhibited CYP3A4 activity with IC 50 values of 32.02 μM and 1.39 μM, respectively. SCH or GOM at concentrations up to 100 μM 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 GOM could affect cellular drug metabolism in addition to drug uptake.