Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide |
| |
Authors: | Pekthong D Martin H Abadie C Bonet A Heyd B Mantion G Richert L |
| |
Institution: | 1. Laboratoire de Toxicologie Cellulaire, EA 3921 “Optimisation Métabolique et Cellulaire”, UFR des Sciences Médicales et Pharmaceutiques, Besançon, France;2. KaLy-Cell, Temis Innovation, Besançon, France;3. Service de Chirurgie Viscérale et Digestive, Centre de Transplantation Hépatique, EA 3921 “Optimisation Métabolique et Cellulaire”, Hôpital Jean Minjoz, Besançon, France |
| |
Abstract: | The inhibitory effect of Andrographis paniculata extract (APE) and andrographolide (AND), the most medicinally active phytochemical in the extract, on hepatic cytochrome P450s (CYPs) activities was examined using rat and human liver microsomes. For this purpose, CYP1A2-dependent ethoxyresorufin-O-deethylation, CYP2B1-dependent benzyloxyresorufin-O-dealkylation, CYP2B6-dependent bupropion hydroxylation, CYP2C-dependent tolbutamide hydroxylation, CYP2E1-dependent p-nitrophenol hydroxylation and CYP3A-dependent testosterone 6 beta-hydroxylation activities, were determined in the presence and absence of APE or AND (0-200 microM). APE inhibited ethoxyresorufin-O-deethylation activity in rat and human liver microsomes, with apparent Ki values of 8.85 and 24.46 microM, respectively. In each case, the mode of inhibition was noncompetitive. APE also inhibited tolbutamide hydroxylation both in rat and human microsomes with apparent Ki values of 8.21 and 7.51 microM, respectively and the mode of inhibition was mixed type. In addition, APE showed a competitive inhibition only on CYP3A4 in human microsomes with Ki of 25.43 microM. AND was found to be a weak inhibitor of rat CYP2E1 with a Ki of 61.1 microM but did not affect human CYP2E1. In conclusion, it cannot be excluded from the present study that APE could cause drug-drug interactions in humans through CYP3A and 2C9 inhibition. |
| |
Keywords: | BROD benzyloxyresorufin-O-deethylation BuOH bupropion hydroxylation CYP cytochrome P450 EROD ethoxyresorufin-O-deethylation HLM human liver microsome PNP-OH paranitrophenol hydroxylation TolOH tolbutamide hydroxylation 6βTesto-OH testosterone 6β-hydroxylation |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|