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 M, respectively, as well as efavirenz 8-hydroxylase activity, with K i values of 22 and 26 M, 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.Herbal medicines have received much attention as alternatives to conventional clinical therapy, and consumption of herbal medicines in Asian, North American, and European countries has increased dramatically in recent years (Eisenberg et al., 1998;De Smet and Debeer, 2002). A recent report indicates that as many as 16% of prescription drug users consume herbal dietary supplements (Kaufman et al., 2002). With the widespread use of herbal medicines, the risk of herb-drug interactions is a growing medical issue, and physicians and pharmacists are concerned about adverse effects such as hepatotoxicity and drug interactions (Kaplowitz, 1997;Suchard et al., 2004). Several medicinal herbs, including St. John's wort (Henderson et al., 2002;Mills et al., 2004), ginkgo biloba (Yin et al., 2004), and kava (Anke and Ramzan, 2004), have been reported to cause herb-drug interactions. Interactions among therapeutic drugs as well as interactions of drugs with food and herbal medicines have attracted attention.The modulation of drug-metabolizing enzymes is one of the main mechanisms of drug interactions (Guengerich, 1997). Cytochrome P450 (P450) monooxygenases are probably the most important enzymes in the detoxification and bioactivation of a number of therapeutic drugs. The P450 family comprises a group of enzymes with broad substrate specificity, which leads to herb-induced drug interactions with some P450 substrates (Ueng et al., 2002). In recent years, in vitro systems using human liver microsome...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.