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 (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 microM and 1.39 microM, respectively. SCH or GOM at concentrations up to 100 microM 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.
Wan
C-K
CK
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tse
A K
AK
Yu
Z-L
ZL
Zhu
G-Y
GY
Wang
H
H
Fong
D W F
DW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D034242:Cyclooctanes / Q000302:isolation & purification / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004149:Dioxoles / Q000302:isolation & purification / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D005638:Fruit; D005978:Glutathione / Q000378:metabolism*; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034242:Cyclooctanes; D065692:Cytochrome P-450 CYP3A Inhibitors; D004149:Dioxoles; D017705:Lignans; D010936:Plant Extracts; C520474:schisandrol A; C033585:schizandrol B; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D005978:Glutathione