Publication: Inhibition effects of Vernonia cinerea active compounds against cytochrome P450 2A6 and human monoamine oxidases, possible targets for reduction of tobacco dependence
Issued Date
2015-01-04
Resource Type
ISSN
18800920
13474367
13474367
Other identifier(s)
2-s2.0-84926306459
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Drug Metabolism and Pharmacokinetics. Vol.30, No.2 (2015), 174-181
Suggested Citation
Aruna Prasopthum, Phisit Pouyfung, Songklod Sarapusit, Ekaruth Srisook, Pornpimol Rongnoparut Inhibition effects of Vernonia cinerea active compounds against cytochrome P450 2A6 and human monoamine oxidases, possible targets for reduction of tobacco dependence. Drug Metabolism and Pharmacokinetics. Vol.30, No.2 (2015), 174-181. doi:10.1016/j.dmpk.2014.12.005 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/36528
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Inhibition effects of Vernonia cinerea active compounds against cytochrome P450 2A6 and human monoamine oxidases, possible targets for reduction of tobacco dependence
Other Contributor(s)
Abstract
Copyright © 2014, The Japanese Society for the Study of Xenobiotics. Abstract The human cytochrome P450 2A6 (CYP2A6) and monoamine oxidases (MAO-A and MAO-B), catalyzing nicotine and dopamine metabolisms, respectively, are two therapeutic targets of nicotine dependence. Vernonia cinerea, a medicinal plant commonly used for treatment of diseases such as asthma and bronchitis, has been shown reducing tobacco dependence effect among tobacco users. In the present study, we found eight active compounds isolated from V. cinerea that comprise inhibitory activity toward CYP2A6 and MAO-A and MAO-B enzymes using activity-guided assays, with coumarin as substrate of CYP2A6 and kynuramine of MAOs. These compounds were three flavones (apigenin, chrysoeriol, luteolin), one flavonol (quercetin), and four hirsutinolide-type sesquiterpene lactones (8α-(2-methylacryloyloxy)-hirsutinolide-13-O-acetate, 8α-(4-hydroxymethacryloyloxy)-hirsutinolide-13-O-acetate, 8α-tigloyloxyhirsutinolide-13-O-acetate, and 8α-(4-hydroxytigloyloxy)-hirsutinolide-13-O-acetate). Modes and kinetics of inhibition against the three enzymes were determined. Flavonoids possessed strong inhibitory effect on CYP2A6 in reversible mode, while inhibition by hirsutinolides was mechanism-based (NADPH-, concentration-, and time-dependence) and irreversible. Inhibition by hirsutinolides could not be reversed by dialysis and by addition of trapping agents or potassium ferricyanide. Flavonoids inhibited MAOs with variable degrees and were more prominent in inhibition toward MAO-A than hirsutinolides, while two of hirsutinolides inhibited MAO-B approximately comparable to two flavonoids. These results could have implications in combination of drug therapy for smoking cessation.