<b><i>In vitro</i></b>metabolism of eupatilin by multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes

Lee, H S; Ji, Hye Young; Park, E J; Kim, S Y

doi:10.1080/00498250701534877

Cited by 27 publications

(11 citation statements)

References 23 publications

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“…The UGT1A7 isoform is not expressed in the liver but in several extrahepatic tissues (ie lung, upper gastrointestinal tract), mostly devoted to the front‐line glucuronidation of numerous xenobiotics, including some molecules (ie dietary components) that display anticancer, anti‐inflammation and anti‐oxidative proprieties as flavones . From the present findings, the low‐activity UGT1A7*3 allele appeared to protect towards HCC development, independent of viral status.…”

Section: Discussionmentioning

confidence: 55%

UGT1A polymorphisms as genetic biomarkers for hepatocellular carcinoma risk in Caucasian population

Mattia

Cecchin

Polesel

et al. 2017

Liver International

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Section: Discussionmentioning

confidence: 55%

UGT1A polymorphisms as genetic biomarkers for hepatocellular carcinoma risk in Caucasian population

Mattia

Cecchin

Polesel

et al. 2017

Liver International

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“…Eupatilin, a pharmacologically active flavone of the Artemisia species, is metabolized to jaceosidin by CYP1A2 and CYP2C8-mediated O-demethylation, and further metabolized to eupatilin glucuronide and jaceosidin glucuronide by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 ( Fig. 1) (Lee et al, 2007;Song et al, 2010). Curcumin is metabolized by UGT1A8, UGT1A9, UGT1A10, and UGT2B7 (Hoehle et al, 2007).…”

Section: Metabolism By Cytochrome P450 and Uridine Diphosphate Glucurmentioning

confidence: 98%

Evaluation of metabolism-mediated herb-drug interactions

Park

et al. 2011

Arch. Pharm. Res.

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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.

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“…The major enzymes catalyzing resveratrol-3-O and 4'-O conjugation are members of UGT 1A sub family and include UGT1A1 and 1A9, with minor contributions by UGT1A10 [26][27]. The glucuronidation of eupatilin, active flavone derived from Artemisia plants, was catalyzed from UGT1A1, 1A3, 1A7, 1A8, 1A9, and 1A10 [28]. The phenolic glucuronidation of the curcuminoids was predominantly catalyzed by hepatic UGT1A1 and intestinal UGT1A8 and 1A10, whereas UGT1A9, 2B7, and 1A8 exhibited high activities for hexahydro-curcuminoids [22].…”

Section: Uridine Diphosphate Glucuronosyltransferase (Ugt)-mediated Cmentioning

confidence: 99%

Disposition Pathways and Pharmacokinetics of Herbal Medicines in Humans

He¹,

Li²,

Liu³

et al. 2012

CMC

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Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. To retrieve relevant data, the authors have searched through computer-based literatures by full text search in Medline (via Pubmed), ScienceDirect, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO), CrossRef Search and Embase (all from inception to May 2010). Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein (P-gp) which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger. The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action. Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a full understanding of their pharmacokinetic profiles. To optimize the use of herbal remedies, further clinical studies to explore their biological fate including the disposition pathways and kinetics in the human body are certainly needed.

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In vitrometabolism of eupatilin by multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes

Cited by 27 publications

References 23 publications

UGT1A polymorphisms as genetic biomarkers for hepatocellular carcinoma risk in Caucasian population

UGT1A polymorphisms as genetic biomarkers for hepatocellular carcinoma risk in Caucasian population

Evaluation of metabolism-mediated herb-drug interactions

Disposition Pathways and Pharmacokinetics of Herbal Medicines in Humans

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