TABLE 1.
Comparison of IC50 values for four key flavonolignans from milk thistle using (S)-warfarin 7-hydroxylation as an index of CYP2C9 activity
Values represent the estimate ± S.E.
| Enzyme Source | IC50 |
|||
|---|---|---|---|---|
| Silybin A | Silybin B | Isosilybin A | Isosilybin B | |
| μM | ||||
| Reversible inhibition experimental design | ||||
| HLMs | 18 ± 2.2 | 8.2 ± 1.4a | >100 | 74 ± 11 |
| CYP2C9*1 | 12 ± 0.9 | 6.7 ± 0.5a | N.D. | N.D. |
| CYP2C9*2 | 19 ± 1.7 | 9.3 ± 0.9a | N.D. | N.D. |
| CYP2C9*3 | 9.3 ± 2.0b | 2.4 ± 0.6a,b | N.D. | N.D. |
| IC50 shift experimental design | ||||
| HLMs (−NADPH)c | 18 ± 0.7 | 7.8 ± 0.5 | N.D. | N.D. |
| HLMs (+NADPH)d | 17 ± 0.7 | 7.9 ± 0.9 | N.D. | N.D. |
N.D., not determined.
a
Significantly different from the IC50 for silybin A (p < 0.05, Student's t test of two independent samples).
b
Significantly different from the IC50 obtained with HLMs, CYP2C9*1, and CYP2C9*2 (p < 0.05, one-way ANOVA, followed by Tukey's test) for a given inhibitor.
c
NADPH was absent during the primary incubation.
d
NADPH was present during the primary incubation.