TABLE 2

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.

Extract	RDI	UGT1A4		UGT1A6		UGT1A9
Extract	RDI	Rough IC₅₀	VDI	Rough IC₅₀	VDI	Rough IC₅₀	VDI
	mg	μg/ml	l/dose	μg/ml	l/dose	μg/ml	l/dose
Black cohosh	40	69.7 ± 4.8	0.6	N.A.	N.A.	321.6 ± 102.2	0.1
Cranberry	1000	742.7 ± 118.7	1.3	>1000	<1.0	260.5 ± 33.0	3.8^{^a}
Echinacea	400	116.1 ± 25.1	3.4	241.0 ± 23.4	1.7	858.3 ± 158.7	0.5
Garlic	1000	N.A.	N.A.	N.A.	N.A.	N.A.	N.A.
Ginkgo biloba	240	268.2 ± 48.9	0.9	N.A.	N.A.	PB^{^b}	PB
Acid-hydrolyzed Ginkgo biloba	240	Interf^{^c}		N.A.	N.A.	PB	PB
Ginseng	550	368.4 ± 66.6	1.5	N.A.	N.A.	298.6 ± 29.1	1.8
Acid-hydrolyzed ginseng	550	288.0 ± 42.8	1.9	>1000	<0.6	524.3 ± 60.5	1.0
Milk thistle	600	Interf		66.9 ± 3.5	9.0^{^a}	35.9 ± 4.3	16.7^{^a}
Saw palmetto	320	70.6 ± 9.3	4.5	131.8 ± 21.5	2.4^{^a}	N.A.	N.A.
Valerian	1000	406.5 ± 35.3	2.5	>1000	<1.0	N.A.	N.A.
EGCG	250	34.39 ± 4.1	7.3^{^a}	183.6 ± 29.8	1.4	N.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.