Table 2.
In vitro inhibition, by XueBiJing compounds, of human drug metabolizing enzymes and transporters.
| Drug metabolizing enzymes [substrate→metabolite] or transporters [substrate] | IC50 values of XueBiJing compounds (μmol/L) |
||||||
|---|---|---|---|---|---|---|---|
| X3 | X7 | X8 | X9 | X10 | X11 | X12 | |
| CYP2C9 [MFC→HFC] | 93 ± 18 | – | – | – | 75 ± 13 | – | – |
| CYP2C19 [CEC→CHC] | – | – | – | – | 19 ± 4 | – | – |
| UGT1A1 [E2→E23βG] | – | – | – | – | 10 ± 1 | – | – |
| UGT1A6 [4-MU→4-MUG] | – | – | – | – | 15 ± 1 | – | – |
| UGT1A9 [4-MU→4-MUG] | 74 ± 20 | – | – | – | 3 ± 1 | – | – |
| UGT2B15 [SENI→S7G] | – | – | – | – | 92 ± 25 | – | – |
| OATP1B1 [E217βG] | – | – | – | – | 38 ± 3 | – | – |
| OATP1B3 [E217βG] | – | – | – | – | 18 ± 4 | – | – |
| OAT1 [PAH] | – | 11 ± 3 | 78 ± 14 | 106 ± 26 | – | – | 2 ± 0 |
| OAT2 [prostaglandin F2α] | – | 51 ± 5 | – | – | – | – | 12 ± 1 |
| OAT3 [estrone-3-sulfate] | – | – | – | – | 31 ± 8 | 28 ± 7 | – |
Using pooled human liver microsomes, the XueBiJing compounds X3 and X10 (each at 100 μmol/L) exhibited the percentage inhibition of CYP2C9 60 ± 3% (by preincubation with NADPH)/56 ± 0% (by preincubation without NADPH) and 50 ± 3%/79 ± 2%, respectively. X10 (at 100 μmol/L) exhibited such percentage inhibition of CYP2C19 68 ± 16%/77 ± 11%. X3, oxypaeoniflorin; X7, senkyunolide G; X8, tanshinol; X9, 3-O-methyltanshinol; X10, salvianolic acid B; X11, protocatechuic acid; X12, ferulic acid; CEC: 3-cyano-7-ethoxycoumarin; CHC: 3-cyano-7-hydroxycoumarin; HFC: 7-hydroxytrifluoromethylcoumarin; MFC: 7-methoxy-4- trifluoromethylcoumarin; E2: β-estradiol; E23βG: β-estradiol-3-(β-d-glucuronide); 4-MU: 4-methylumbeliferone; 4-MUG: 4-methylumbelliferyl-β-d-glucuronide; SENI: senkyunolide I; S7G: senkyunolide I-7-O-β-glucuronide; E217βG, estradiol-17β-d-glucuronide; PAH, para-aminohippuric acid. Data are expressed as the mean ± SD (n = 3).