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
Enzyme Source	Silybin A	Silybin B	Isosilybin A	Isosilybin B
	μM
Reversible inhibition experimental design
HLMs	18 ± 2.2	8.2 ± 1.4^a	>100	74 ± 11
CYP2C9*1	12 ± 0.9	6.7 ± 0.5^a	N.D.	N.D.
CYP2C9*2	19 ± 1.7	9.3 ± 0.9^a	N.D.	N.D.
CYP2C9*3	9.3 ± 2.0^b	2.4 ± 0.6^a,^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.