Ismail S, Hanapi NA, Ab Halim MR, Uchaipichat V, Mackenzie PI.
Centre for Drug Research, Universiti Sains Malaysia, 11800, Penang,
Malaysia. sabaris@usm.my
The effects of Andrographis paniculata and Orthosiphon stamineus
extracts on the in vitro glucuronidation of 4-methylumbelliferone
(4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7,
UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential
inhibitory effects of both of the extracts on the activity of each of
the UGT isoforms were investigated using 4MU as the substrate.
Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor,
MgCl(2), cell lysate of respective isoform, and 4MU at the approximate
apparent K(m) or S(50) value of each isoform. Final concentrations of
Andrographis paniculata and Orthosiphon stamineus extracts used were
0.025, 0.25, 2.5, 25 and 50 microg/mL and 0.01, 0.10, 1.0, 10 and 50
microg/mL respectively. Both extracts variably inhibited the activity
of most of the isoforms in a concentration dependent manner.
Andrographis paniculata extract was the better inhibitor of all the
isoforms studied (IC(50) 1.70 microg/mL for UGT1A3, 2.57 microg/mL for
UGT1A8, 2.82 microg/mL for UGT2B7, 5.00 micorg/mL for UGT1A1, 5.66
microg/mL for UGT1A6, 9.88 microg/mL for UGT1A7 and 15.66 microg/mL
for UGT1A10). Both extracts showed less than 70% inhibition of
UGT2B15, so the IC(50) values were >50 microg/mL. The inhibition of
human UGTs by Andrographis paniculata and Orthosiphon stamineus
extracts in vitro suggests a potential for drug-herbal extract
interactions in the therapeutic setting.
PMID: 20657500 [PubMed - in process]
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