Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT IsoformsReportar como inadecuado




Effects of Andrographis paniculata and Orthosiphon stamineus Extracts on the Glucuronidation of 4-Methylumbelliferone in Human UGT Isoforms - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1

Centre for Drug Research, Universiti Sains Malaysia, 11800, Penang, Malaysia

2

Department of Clinical Pharmacology, Flinders University, Adelaide, Australia





*

Author to whom correspondence should be addressed.



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, 9.88 μg-mL for UGT1A7 and 15.66 μg-mL for UGT1A10. Both extracts showed less than 70% inhibition of UGT2B15, so the IC50 values were 50μg-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.

Keywords: UGT; inhibition; herbal extracts; Orthosiphon stamineus; Andrographis paniculata UGT; inhibition; herbal extracts; Orthosiphon stamineus; Andrographis paniculata





Autor: Sabariah Ismail 1,* , Nur Aziah Hanapi 1, Mohd Rohaimi Ab Halim 1, Verawan Uchaipichat 2 and Peter I. Mackenzie 2

Fuente: http://mdpi.com/



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