title: In vitro determination of the effect of Andrographis paniculata extracts and andrographolide on human hepatic cytochrome P450 activities.
abstract: We investigated the effects of Andrographis paniculata (AP) extracts and andrographolide on the catalytic activity of three human cDNA-expressed cytochrome P450 enzymes: CYP2C9, CYP2D6 and CYP3A4. In vitro probe-based high performance liquid chromatography assays were developed to determine CYP2C9-dependent tolbutamide methylhydroxylation, CYP2D6-dependent dextromethorphan O-demethylation and CYP3A4-dependent testosterone 6β-hydroxylation activities in the presence and absence of AP extracts and andrographolide. Our results indicate that AP ethanol and methanol extracts inhibited CYP activities more potently than aqueous and hexane extracts across the three isoforms. Potent inhibitory effects were observed on CYP3A4 and CYP2C9 activities (K (i) values below 20 μg/ml). Andrographolide was found to exclusively but weakly inhibit CYP3A4 activity. In conclusion, data presented in this study suggest that AP extracts have the potential to inhibit CYP isoforms in vitro. There was, however, variation in the potency of inhibition depending on the extracts and the isoforms investigated.
authors.affiliation: School of Pharmacy and Health Sciences, International Medical University, 57000, Kuala Lumpur, Malaysia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.forename: Badrul Amini
authors.initials: BA
authors.lastname: Abd-Rashid
authors.forename: Zakiah
authors.initials: Z
authors.lastname: Ismail
authors.forename: Rusli
authors.initials: R
authors.lastname: Ismail
authors.forename: Joon Wah
authors.initials: JW
authors.lastname: Mak
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Pook
authors.forename: Hui Meng
authors.initials: HM
authors.lastname: Er
authors.forename: Chin Eng
authors.initials: CE
authors.lastname: Ong
mesh_terms: D035685:Andrographis / Q000737:chemistry*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004224:Diterpenes; D010936:Plant Extracts; C030419:andrographolide; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human