Determination of inhibitory potency of selected UGT1A4, UGT1A6, and UGT1A9 herbal inhibitors

Extracts were selected if their VDI on the basis of rough IC50 values exceeded 4 liters for UGT1A4 or 2 liters for UGT1A6 and UGT1A9. Several concentrations of each extract were coincubated with alamethicin-activated HLM and TFP (for UGT1A4), serotonin (for UGT1A6), or MPA (for UGT1A9). The percentage of remaining activity was measured as the formation of each glucuronide in herbal incubation as a percentage of the negative control. IC50 values were calculated by fitting data points to the Hill IC50 equation as described under Materials and Methods. Values reported are best-fit IC50 values ± S.E. The goodness-of-fit r2 value was ≥0.95 for all reported IC50 values. VDI was calculated by dividing the daily intake of each herb by the IC50 value. RDI values were determined on the basis of the PDR for Herbal Medicines (Gruenwald et al., 2004) and commercially available products.

UGT EnzymeExtractRDIIC50VDIH
UGT1A4EGCG25033.8 ±
UGT1A6Milk thistle60059.5 ±
Saw palmetto320103.5 ±
UGT1A9Cranberry1000230.4 ±
Milk thistle60033.6 ±
  • RDI, recommended daily intake.