Evaluation of metabolism-mediated herb-drug interactions

Abstract

As the use of herbal medicines increases, the public health consequences of drug-herb interactions are becoming more significant. Herbal medicines share the same drug metabolizing enzymes and drug transporters, including cytochrome P450 enzymes (CYPs), glucuronosyltransferases (UGTs), and P-glycoprotein, with several clinically important drugs. Interactions of several commonly used herbal medicines, such as Ginko biloba, milk thistle, and St. John's wort, with therapeutic drugs including warfarin, midazolam, alprazolam, indinavir, saquinavir, digoxin, nifedipine, cyclosporine, tacrolimus, irinotecan, and imatinib in humans have been reported. Many of these drugs have very narrow therapeutic indices. As the herb-drug interactions can significantly alter pharmacokinetic and pharmacodynamic properties of administered drugs, the drugs interacting with herbal medicines should be identified by appropriate in vitro and in vivo methods. A good understanding of the mechanisms of herb-drug interactions is also essential for assessing and minimizing clinical risks. In vitro methods are useful for providing mechanistic information and evaluating multiple components in herbal medicines. This review describes major factors affecting the metabolism of herbal medicines, mechanisms of herb-drug interactions mediated by CYPs and UGTs, and several in vitro methods to assess the herb-drug interactions. Finally, drug interactions of Ginkgo biloba and St. John's wort, as representative herbal medicines, are described.

Inhibitory Effects of Aschantin on Cytochrome P450 and Uridine 5′-diphospho-glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

“…Herbal medicines and their constituents may interact with cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferases (UGTs), increasing the possibility of herb-drug interactions [8][9][10][11][12][13]. Several medicinal herbs, including Allium sativum, Camellia sinensis, Ginkgo biloba, Glycyrrhiza glabra, Coptidis rhizoma,Silybi fructus, and St. John's wort are associated with herb-drug interactions attributable to inhibition and/or induction of drug-metabolizing enzymes [14][15][16][17].…”

“…It exhibits various biological activities including peroxynitrite scavenging capacity, inhibition of inducible NO synthetase, antiplasmodial activity, Ca 2+ -antagonistic activity, platelet activating factor-antagonistic activity, and chemo-preventative or therapeutic activity mediated via inhibition of mTOR kinase [2][3][4][5][6][7]. Herbal medicines and their constituents may interact with cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferases (UGTs), increasing the possibility of herb-drug interactions [8][9][10][11][12][13]. Several medicinal herbs, including Allium sativum, Camellia sinensis, Ginkgo biloba, Glycyrrhiza glabra, Coptidis rhizoma,Silybi fructus, and St. John's wort are associated with herb-drug interactions attributable to inhibition and/or induction of drug-metabolizing enzymes [14][15][16][17].…”

Inhibitory Effects of Cedrol, β-Cedrene, and Thujopsene on Cytochrome P450 Enzyme Activities in Human Liver Microsomes

“…Botanical drugs share eight human hepatic cytochrome P-450 enzymes (CYPs: 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) with commonly used drugs (Mukherjee et al, 2011;Na et al, 2011;Zhou et al, 2007). Several medicinal herbs, such as garlic, ginkgo, ginseng, milk thistle, licorice, and St. John's wort, reportedly induce herb-drug interactions due to inhibition and/or induction of drug-metabolizing enzymes (Haefeli and Carls, 2014;Kalmes and Blomeke, 2012;Russo et al, 2014;Unger, 2013;Wang et al, 2013; INHIBITORY EFFECTS OF CEDROL, β-CEDRENE, AND THUJOPSENE ON CYPs 1523 FIGURE 1.…”

Metabolism-mediated drug interaction potential of HS-23, a new herbal drug for the treatment of sepsis in human hepatocytes and liver microsomes

“…The underlying mechanisms of herbdrug interactions involve inhibition or induction of cytochrome P450 (CYP) enzymes, UDP-glucuronosyltransferase (UGT) enzymes, and drug transporters (Na et al 2011;Choi et al 2011;Mohamed and Frye 2011;Gouws et al 2012;Zhou et al 2007). Herbal drugs such as ginkgo (Ginkgo biloba), ginseng (Panax ginseng), garlic, licorice (Glycyrrhiza glabra), milk thistle (Silybum marianum), and St. John's wort (Hypericum perforatum) have been reported to cause drug interactions with anticoagulants, antiretroviral drugs, anticancer drugs, immunosuppressants, and antidepressants (He et al 2010;Chen et al 2011;Wu et al 2009;Russo et al 2014;Haefeli and Carls 2014;Unger 2013;Wang et al 2013).…”