Cell System | Preparation | Enzyme or Transporter | Substrate | Incubation Conditions | Metric/Outcome | Reference |
---|---|---|---|---|---|---|
Human hepatocytes | Silymarin | CYP3A4 | Testosterone | 48 h at 100 µM | 50% ↓ in activity | Venkataramanan et al. (2000) |
UGT1A6/9 | 4-Methylumbelliferone | 65% ↓ in activity | ||||
Human hepatocytes | Silibinin | CYP1A2 | NA | 72 h at 100 µM | No change in mRNA or protein expression | Kosina et al. (2005) |
CYP3A4 | ||||||
Human hepatocytes | Silymarin | CYP2C9 | Diclofenac | 72 h at 100 µM | No change in activity | Doehmer et al. (2008) |
CYP3A4 | Testosterone | |||||
Human hepatocytes (three donors per enzyme) | Milk thistle extract | CYP1A2 | 7-Ethoxyresorufin | 72 h at 50 µg/ml | 1.1- to 8.5-fold ↑ in activity | Doehmer et al. (2011) |
CYP2B6 | (S)-Mephenytoin | 0.3- to 2.7-fold ↑ in activity | ||||
CYP2C9 | Diclofenac | 0.7- to 1.6-fold ↑ in activity | ||||
CYP2E1 | Chlorzoxazone | 2.0- to 3.0-fold ↑ in activity | ||||
CYP3A4 | Testosterone | 0.4- to 1.3-fold ↑ in activity | ||||
Caco-2 cells | Silibinin | CYP3A4 | NA | 48 h at 10 µM | 9% ↓ in protein | Budzinski et al. (2007) |
P-gp | 69% ↑ in protein | |||||
Caco-2 cells | Silymarin | P-gp | Digoxin | 1 h at 150 µM | 23% ↑ in accumulation | Zhang and Morris (2003a) |
Vinblastine | 80% ↑ in accumulation | |||||
Caco-2 cells | Silibinin | CYP3A4 | Cortisol | 30 min | No change | Patel et al. (2004) |
P-gp | Ritonavir | No change in transport | ||||
MDR1-transfected MDCK cells | P-gp | Ritonavir | ||||
MDA435/LCC6 cells | Silymarin | P-gp | Daunomycin | 2 h at 50 µM | 4.5-fold ↑ in accumulation | Zhang and Morris (2003b) |
Panc-1 cells | Silymarin | MRP1 | Daunomycin | 2 h at 100 µM | 3.1-fold ↑ in accumulation | Nguyen et al. (2003) |
Vinblastine | 3.3-fold ↑ in accumulation | |||||
BCRP overexpressing membrane vesicles | Milk thistle extract | BCRP | Methotrexate | 2 min at 1000 µg/ml | 45% ↓ in transport | Tamaki et al. (2010) |
MCF-7 MX100 cells | Silymarin | BCRP | Mitoxantrone | 15-min preincubation, 30-min coincubation | EC50, 34 µM | Zhang et al. (2004) |
BCRP-transfected MDCK cells | Silymarin | BCRP | Rosuvastatin | 1 h | Ki, 98 µM | Deng et al. (2008) |
OATP1B1-transfected Xenopus oocytes | OATP1B1 | 30 min | Ki, 0.93 µM | |||
HEK293-OATP1B1 | Silymarin | OATP1B1 | Estradiol-17-β-glucuronide | 3 min | IC50, 1.3 µM | Kock et al. (2013) |
HEK293-OATP1B3 | OATP1B3 | IC50, 2.2 µM | ||||
MDCKII-OATP2B1 | OATP2B1 | Estrone-3-sulfate | IC50, 0.3 µM | |||
HepG2, MCF-7 | trans-Resveratrol | CYP1A1 | NA | 6 h | Concentration-dependent ↓ in TCDD-induced CYP1A1 mRNA and 47% ↓ in basal CYP1A1 mRNA (HepG2), concentration-dependent ↓ in DMBA-induced CYP1A1 mRNA (MCF-7) | Ciolino et al. (1998) and Ciolino and Yeh (1999) |
Human bronchial epithelial BEAS-2B and BEP2D cells | trans-Resveratrol | CYP1A1 and CYP1B1 | Benzo[a]pyrene | 24 or 72 h | 56% ↓ CYP1A1 mRNA (24 h), 70% ↓ CYP1A1 mRNA (72 h) | Berge et al. (2004) |
Caco-2 cells | trans-Resveratrol | UGT1A1 | NA | 72 h | 4-fold ↑ in UGT1A1 mRNA | Iwuchukwu et al. (2011) |
NA, not applicable.