title: In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity.
abstract: This study was designed to investigate eight herbal active constituents (andrographolide, asiaticoside, asiatic acid, madecassic acid, eupatorin, sinensetin, caffeic acid, and rosmarinic acid) on their potential inhibitory effects on human cytochrome P450 1A2 (CYP1A2) activity. A fluorescence-based enzyme assay was performed by co-incubating human cDNA-expressed CYP1A2 with its selective probe substrate, 3-cyano-7-ethoxycoumarin (CEC), in the absence or presence of various concentrations of herbal active constituents. The metabolite (cyano-hydroxycoumarin) formed was subsequently measured in order to obtain IC50 values. The results indicated that only eupatorin and sinensetin moderately inhibited CYP1A2 with IC50 values of 50.8 and 40.2 μM, while the other active compounds did not significantly affect CYP1A2 activity with IC50 values more than 100 μM. Ki values further determined for eupatorin and sinensetin were 46.4 and 35.2 μM, respectively. Our data indicated that most of the investigated herbal constituents have negligible CYP1A2 inhibitory effect. In vivo studies however may be warranted to ascertain the inhibitory effect of eupatorin and sinensetin on CYP1A2 activity in clinical situations.
authors.affiliation: Department of Biomedical Science, The University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor Darul Ehsan, Malaysia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: School of Medical Sciences, International Medical University, 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
authors.forename: Kai Hung
authors.initials: KH
authors.lastname: Tiong
authors.affiliation: Herbal Medicine Research Unit, Division of Biochemistry, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
authors.forename: Badrul Amini
authors.initials: BA
authors.lastname: Abd-Rashid
authors.affiliation: Herbal Medicine Research Unit, Division of Biochemistry, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
authors.forename: Zakiah
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Centre of Excellence for Research in AIDS (CERiA), Universiti Malaya, Level 17 Wisma R&D, Jalan Pantai Baru, 59990 Kuala Lumpur, Malaysia.
authors.forename: Rusli
authors.initials: R
authors.lastname: Ismail
authors.affiliation: School of Medical Sciences, International Medical University, 126, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
authors.forename: Joon Wah
authors.initials: JW
authors.lastname: Mak
authors.affiliation: School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: ceong98@hotmail.com.
authors.forename: Chin Eng
authors.initials: CE
authors.lastname: Ong
mesh_terms: D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065609:Cytochrome P-450 CYP1A2 Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D005419:Flavonoids; D010936:Plant Extracts; C059295:sinensetin; C103110:eupatorin; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2
keywords: CYP1A2; Fluorescence-based enzyme assay; Herbal active constituents; Inhibitory effect