Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT Isoforms.docVIP

Molecules 2010, 15, 3578-3592; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT Isoforms Sabariah Ismail 1,*, Nur Aziah Hanapi 1, Mohd Rohaimi Ab Halim 1, Verawan Uchaipichat 2 and Peter I. Mackenzie 2 1 Centre for Drug Research, Universiti Sains Malaysia, 11800, Penang, Malaysia 2 Department of Clinical Pharmacology, Flinders University, Adelaide, Australia; E-Mails: verawan.uchaipichat@.au (V.U.); peter.mackenzie@.au (P.I.M.) * Author to whom correspondence should be addressed; E-Mail: sabaris@usm.my; Tel.: +60 Fax: +60 Received: 9 March 2010; in revised form: 16 April 2010 / Accepted: 20 April 2010 / Published: 14 May 2010 Abstract: 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, MgCl2, cell lysate of respective isoform, and 4MU at the approximate apparent Km or S50 value of each isoform. Final concentrations of Andrographis paniculata and Orthosiphon stamineus extracts used were 0.025, 0.25, 2.5, 25 and 50 μg/mL and 0.01, 0.10, 1.0, 10 and 50 μg/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 (IC50 1.70 μg/mL for UGT1A3, 2.57 μg/mL for UGT1A8, 2.82 μg/mL for UGT2B7, 5.00 μg/mL for UGT1A1, 5.66 μg/mL for UGT1A6,