title: Identification and characterization of potent CYP2B6 inhibitors in Woohwangcheongsimwon suspension, an herbal preparation used in the treatment and prevention of apoplexy in Korea and China.
abstract: Woohwangcheongsimwon is a traditional medicine for treating hypertension, arteriosclerosis, coma, and stroke in China and Korea. To assess potential interactions of herb and drug metabolism, commercially available Woohwangcheongsimwon suspensions were examined for their potential to inhibit the activity of nine human cytochrome P450 enzymes. The Woohwangcheongsimwon suspensions showed strong inhibition of CYP2B6 activity. To identify individual constituents with inhibitory activity, the suspension was partitioned using hexane, ethyl acetate, and dichloromethane, and each fraction was tested for its inhibitory effect on CYP2B6-catalyzed bupropion hydroxylation. The hexane fraction possessed inhibitory activity, and gas chromatography/mass spectrometry analysis identified borneol and isoborneol as major constituents of the hexane fraction. These two terpenoids moderately inhibited CYP2B6-catalyzed bupropion hydroxylase activity in a competitive manner, with K(i) values of 9.5 and 5.9 microM, respectively, as well as efavirenz 8-hydroxylase activity, with K(i) values of 22 and 26 microM, respectively. Additionally, reconstituted mixtures of borneol and isoborneol, at the same concentrations as in the Woohwangcheongsimwon suspension, had comparable potency in inhibiting bupropion hydroxylation. These in vitro data indicate that Woohwangcheongsimwon preparations contain constituents that can potently inhibit the activity of CYP2B6 and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo.
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea.
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Kim
authors.forename: Kwon-Bok
authors.initials: KB
authors.lastname: Kim
authors.forename: Hei-Young
authors.initials: HY
authors.lastname: Ku
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Hoon
authors.initials: H
authors.lastname: Choi
authors.forename: Joon-Kwan
authors.initials: JK
authors.lastname: Moon
authors.forename: Byeoung-Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Yea
authors.forename: Choong-Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.forename: Kwang-Hyeon
authors.initials: KH
authors.lastname: Liu
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001892:Camphanes / Q000494:pharmacology*; D002681:China; D065702:Cytochrome P-450 CYP2B6; D041743:Herb-Drug Interactions; D006801:Humans; D007723:Korea; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy / Q000517:prevention & control; D013535:Suspensions
chemical_list: D001892:Camphanes; D028321:Plant Preparations; D013535:Suspensions; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C022871:isoborneol