title: Inhibitory and inductive effects of Phikud Navakot extract on human cytochrome P450.
abstract: Effects of the hydroethanolic extract of Phikud Navakot (PN), a Thai traditional remedy, on human cytochrome P450s (CYPs) were investigated in vitro. Selective substrates of CYPs were used to investigate the effects and kinetics of PN on CYP inhibition using human liver microsomes. Primary human hepatocytes were used to assess the inductive effects of PN on CYP enzyme activities and protein expressions. The results showed that PN inhibited the activities of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 with half maximal inhibitory concentration (IC50) values of 13, 62, 67, and 88 μg/mL, respectively. Meanwhile, it had no effect on the activities of CYP2C19 and CYP2E1 (IC50 > 1 mg/mL). PN exhibited competitive inhibition of CYP1A2 (Ki = 34 μg/mL), mixed type inhibition of CYP2C9 and CYP2D6 (Ki = 80 and 12 μg/mL, respectively), and uncompetitive inhibition of CYP3A4 (Ki = 150 μg/mL). PN did not have an inductive effect on CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in primary human hepatocytes, which is an advantageous characteristic of the extract. However the extract may cause herb-drug interactions via inhibition of CYP1A2, CYP2C9, CYP2D6 and CYP3A4, and precautions should be taken when PN is coadministered with drugs that are metabolized by these CYP enzymes.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Abhiruj
authors.initials: A
authors.lastname: Chiangsom
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: somsong.l@chula.ac.th.
authors.forename: Somsong
authors.initials: S
authors.lastname: Lawanprasert
authors.affiliation: Department of Drug Safety Sciences, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Oda
authors.affiliation: National Nanotechnology Center, National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand.
authors.forename: Kornphimol
authors.initials: K
authors.lastname: Kulthong
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Rataya
authors.initials: R
authors.lastname: Luechapudiporn
authors.affiliation: Department of Drug Safety Sciences, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
authors.affiliation: National Nanotechnology Center, National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, Thailand. Electronic address: rawiwan@nanotec.or.th.
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Maniratanachote
mesh_terms: D002478:Cells, Cultured; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D010936:Plant Extracts / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; C000603668:phikud navakot; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Drug interaction; Induction; Inhibition; Phikud Navakot