Effect of commonly used herbal extracts on UGT1A4, UGT1A6, and UGT1A9 activity

Each herbal extract was coincubated at three concentrations with TFP (for UGT1A4), serotonin (for UGT1A6), and MPA (for UGT1A9) and HLM. Formation of TFPG, serotonin glucuronide, and MPAG were used as index reactions for activity of UGT1A4, UGT1A6, and UGT1A9 enzyme activities, respectively. Formation of glucuronides was compared in incubations with herbal extract with negative control incubations. Data represent best-fit IC50 values ± S.E. The goodness-of-fit r2 value was >0.9 for all reported IC50 values. VDI was calculated by dividing the daily intake of each herb by the rough IC50 value. RDI values were determined on the basis of the PDR for Herbal Medicines (Gruenwald et al., 2004) and commercially available products.

Rough IC50VDIRough IC50VDIRough IC50VDI
Black cohosh4069.7 ± 4.80.6N.A.N.A.321.6 ± 102.20.1
Cranberry1000742.7 ± 118.71.3>1000<1.0260.5 ± 33.03.8a
Echinacea400116.1 ± 25.13.4241.0 ± 23.41.7858.3 ± 158.70.5
Ginkgo biloba240268.2 ± 48.90.9N.A.N.A.PBbPB
Acid-hydrolyzed Ginkgo biloba240InterfcN.A.N.A.PBPB
Ginseng550368.4 ± 66.61.5N.A.N.A.298.6 ± 29.11.8
Acid-hydrolyzed ginseng550288.0 ± 42.81.9>1000<0.6524.3 ± 60.51.0
Milk thistle600Interf66.9 ± 3.59.0a35.9 ± 4.316.7a
Saw palmetto32070.6 ± 9.34.5131.8 ± 21.52.4aN.A.N.A.
Valerian1000406.5 ± 35.32.5>1000<1.0N.A.N.A.
EGCG25034.39 ± 4.17.3a183.6 ± 29.81.4N.A.N.A.
  • N.A., data points did not fit the IC50 curve.

  • a Volume/dose index values that exceed the cutoff for further investigation.

  • b PB, IC50 values for inhibition of UGT1A9 by ginkgo and acid-hydrolyzed ginkgo extracts have been reported previously (Mohamed and Frye, 2010). Ginkgo and acid-hydrolyzed ginkgo extracts inhibited MPAG formation in HLM with IC50 values of 84.3 ± 11.6 and 20.9 ± 3.6 μg/ml, respectively. For a dose of 240 mg, this would result in VDI of 2.9 and 11.4 l/dose for unhydrolyzed and acid-hydrolyzed ginkgo extracts, respectively.

  • c Interf: addition of herb interfered with florescence detection of glucuronide.