Green Tea (Camellia sinensis) 19124972
Inhibitory effects of commonly used herbal extracts on UDP-glucuronosyltransferase 1A4, 1A6, and 1A9 enzyme activities CSV JSON

The aim of this study was to investigate the effect of commonly used botanicals on UDP-glucuronosyltransferase (UGT) 1A4, UGT1A6, and UGT1A9 activities in human liver microsomes. The extracts screened were black cohosh, cranberry, echinacea, garlic, ginkgo, ginseng, milk thistle, saw palmetto, and valerian in addition to the green tea catechin epigallocatechin gallate (EGCG). Formation of trifluoperazine glucuronide, serotonin glucuronide, and mycophenolic acid phenolic glucuronide was used as an index reaction for UGT1A4, UGT1A6, and UGT1A9 activities, respectively, in human liver microsomes. Inhibition potency was expressed as the concentration of the inhibitor at 50% activity (IC(50)) and the volume in which the dose could be diluted to generate an IC(50)-equivalent concentration [volume/dose index (VDI)]. Potential inhibitors were EGCG for UGT1A4, milk thistle for both UGT1A6 and UGT1A9, saw palmetto for UGT1A6, and cranberry for UGT1A9. EGCG inhibited UGT1A4 with an IC(50) value of (mean ± S.E.) 33.8 ± 3.1 μg/ml. Milk thistle inhibited both UGT1A6 and UGT1A9 with IC(50) values of 59.5 ± 3.6 and 33.6 ± 3.1 μg/ml, respectively. Saw palmetto and cranberry weakly inhibited UGT1A6 and UGT1A9, respectively, with IC(50) values >100 μg/ml. For each inhibition, VDI was calculated to determine the potential of achieving IC(50)-equivalent concentrations in vivo. VDI values for inhibitors indicate a potential for inhibition of first-pass glucuronidation of UGT1A4, UGT1A6, and UGT1A9 substrates. These results highlight the possibility of herb-drug interactions through modulation of UGT enzyme activities. Further clinical studies are warranted to investigate the in vivo extent of the observed interactions.

PMID:21632963

21632963

1 . Inhibition of UGT1A9 by Epigallocatechin Gallate (id=NPDI-mzhpNw)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used — >20% inhibiton vs. control

mycophenolic acid

epigallocatechin gallate 19058494

mycophenolic acid 7-o-glucuronide

  • UGT1A9

Cell fraction Pooled human liver microsomes -7999662

Results

Percent inhibition was estimated from Fig. 1. Epigallocaetchin gallate at 250 mg in 53 and 5.3 L did not inhibit UGT1A9-mediated mycophenolic acid 7-O-glucuronide formation.

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.16 mg/mL

Commercially available

100 µL

30 min

UDPGA

Not available

Not available

240 µM

250 mg in 0.53 L

2 . Inhibition of UGT1A6 by Epigallocatechin Gallate (id=NPDI-Dg01cQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used — >20% inhibiton vs. control

serotonin

epigallocatechin gallate 19058494

serotonin glucuronide

  • UGT1A6

Cell fraction Pooled human liver microsomes -7999662

Results

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.5 mg/mL

Commercially available

100 µL

60 min

UDPGA

8 mM

250 mg in 53, 5.3, and 0.53 L

3 . Inhibition of UGT1A4 by Epigallocatechin Gallate (id=NPDI-URZBxQ)

In Vitro Enzyme Inhibition Experiment

Inhibition was detected.  Cutoff used — >20% inhibiton vs. control

trifluoperazine

epigallocatechin gallate 19058494

trifluoperazine glucuronide

  • UGT1A4

Cell fraction Pooled human liver microsomes -7999662

Results

Sample Compound measured Value Measurement Study sequence Additional information N replicates

Experimental Conditions

0.1 mg/mL

Commercially available

20 min

UDPGA

Not available

Not available

60 µM

0.05-1000 µg/mL (estimated from Fig. 2)