Selective Inhibition of Bakuchicin Isolated from Psoralea corylifolia on CYP1A in Human Liver Microsomes
Table 1
Inhibition of 9 CYP-catalyzed activities by bakuchicin in pooled human liver microsomes.
Substrate reaction probes
CYP450 isoforms
Substrate con. (μM)
IC50 (μM)
Without preincubation
With preincubation
Without NADPH
with NADPH
Phenacetin O-deethylation
CYP1A2
80
0.43
0.22
0.22
Bupropion hydroxylation
CYP2B6
50
14.2
16.4
11.5
Paclitaxel hydroxylation
CYP2C8
10
>100
>100
>100
Diclofenac 4′-hydroxylation
CYP2C9
10
>100
>100
>100
Omeprazole 5-hydroxylation
CYP2C19
20
>100
>100
>100
Dextromethorphan O-deethylation
CYP2D6
5
18.2
21.7
15.1
Chlorzoxazone 6-hydroxylation
CYP2E1
50
>100
>100
>100
Midazolam 1′-hydroxylation
CYP3A4
2.5
>100
>100
>100
To determine the inhibitory effects of bakuchicin on the activities of 8 CYPs, HLMs (0.05 mg) were preincubated with β-NADPH for 15 min and then with bakuchicin at 0 to 25 μM for 60 min at 37°C. The data shown are the means of duplicates.
