IC50 values of milk thistle constituents and extracts and other diet-derived constituents toward 4-MU glucuronidation
Apparent IC50 values were determined by fitting eqs. 1, 2, or 3 to observed 4-MU depletion velocities versus nominal inhibitor concentration. Values represent the IC50 estimate ± S.E. via nonlinear least-squares regression using Phoenix WinNonlin (v. 6.3). UGT1A1, UGT1A8, and UGT1A10 refer to HEK293 cell lysates overexpressing respective individual isoforms.
| Constituent/Extract | Enzyme Source (IC50) | ||||
|---|---|---|---|---|---|
| HLMs | HIMs | UGT1A1 | UGT1A8 | UGT1A10 | |
| μM | |||||
| Milk thistle flavonolignans | |||||
| Silybin A | – | 64.8 ± 6.3 | 28.8 ± 5.5 | 5.9 ± 1.4 | 2.7 ± 0.6 |
| Silybin B | 87.3 ± 7.1 | 46.9 ± 6.0 | 27.5 ± 5.7 | 5.8 ± 1.8 | – |
| Isosilybin A | – | – | – | 6.7 ± 1.5 | – |
| Isosilybin B | – | 187 ± 30.9 | 51.1 ± 18.2 | 7.2 ± 1.4 | 5.9 ± 0.9 |
| Silychristin | – | – | – | 2.5 ± 0.6 | 6.0 ± 1.1 |
| Isosilychristin | – | – | 53.5 ± 15.3 | 2.0 ± 0.3 | – |
| Silydianin | 97.7 ± 8.4 | – | 5.3 ± 1.7 | 1.1 ± 0.3 | 6.8 ± 2.2 |
| Milk thistle extracts | |||||
| Silibinin | – | – | 11.1 ± 3.0 | 3.9 ± 1.7 | – |
| Silymarin | 106 ± 7.0 | 40.5 ± 5.3 | – | 4.8 ± 1.6 | – |
| Other diet-derived constituents | |||||
| Naringin | – | – | 14.8 ± 1.8 | 6.3 ± 1.3 | 3.4 ± 0.8 |
| Naringenin | – | – | – | – | 2.8 ± 1.2 |
| Apigenin | – | – | – | – | – |
| Kaempferol | 25.2 ± 2.7 | 11.6 ± 2.9 | 7.9 ± 2.2 | 10.6 ± 1.6 | 0.9 ± 0.4 |
| Quercetin | 70.0 ± 2.4 | 23.4 ± 2.6 | – | – | 8.2 ± 3.3 |
| EGCG | 105 ± 3.6 | 45.8 ± 8.2 | 26.2 ± 5.4 | – | – |
| Prototypic UGT inhibitors | |||||
| Diclofenac | 160 ± 11.3 | 334 ± 74.4 | – | – | – |
| Nicardipine | 160 ± 10.0 | – | – | – | 1.5 ± 0.4 |
–, not determined.