Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro

Wang, Xin; Cheung, Chi-Ngai; Lee, Wayne; Or, Penelope M.Y.; Yeung, John H.K.

doi:10.1016/j.phymed.2010.05.003

Cited by 70 publications

(47 citation statements)

References 39 publications

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“…The dose of TSA needed to cause a 66% inhibition of CYP1A2 activity was calculated as 40 mg/kg (Kuo et al, 2006), and this is equivalent to 20 g/kg Danshen. Moreover, weak or moderate inhibition of TSI, TSA, and CTS was observed for the CYP3A4 enzyme, whereas potent inhibition was observed for CYP1A, CYP2C9, and CYP2E1 (Wang et al, 2010a).…”

Section: Parametermentioning

confidence: 96%

“…In Caco-2 monolayer models and single pass rat intestinal perfusion models, TSA (Yu et al, 2007a), TSB (Yu et al, 2007b), and CTS (Zhang et al, 2006) are also substrates for P-gp and may also be reversing agents of P-gp. Moreover, TSI, TSA, dihydrotanshinone, and CTS are inhibitors of human CYP1A2, 2C9, 2E1, and 3A4, respectively, with different modes of inhibition (Qiu et al, 2008;Wang et al, 2010a). In addition, single-dose treatment with Danshen increased the clearance of tolbutamide, a CYP2C11 probe drug, and decreased the plasma exposure of 4-hydroxy-tolbutamide in rats (Wang et al, 2010b).…”

Section: Introductionmentioning

confidence: 99%

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Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb–drug interactions

Lee¹,

Shin²,

Kim³

et al. 2011

International Journal of Pharmaceutics

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Section: Parametermentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb–drug interactions

Lee¹,

Shin²,

Kim³

et al. 2011

International Journal of Pharmaceutics

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“…In some cases, an inhibitor can exhibit multiple modes of inhibition toward different CYP isoforms. Dihydrotanshinone, found in the Chinese herb Danshen, is a competitive inhibitor of human CYP1A2, CYP2C9, a non-competitive inhibitor of CYP3A4, and an uncompetitive inhibitor of CYP2E1 [27]. …”

Section: Inhibition Of Dmementioning

confidence: 99%

A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?

et al. 2016

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Pregnane X receptor (PXR, NR112) is a xenobiotic receptor whose primary function is to regulate the expression of drug-metabolizing enzymes (DMEs) and drug transporters. Drug-induced PXR activation and subsequent enzyme and transporter induction has been proposed to be an important mechanism for the drug-drug interactions. In addition to activating PXR, many pharmaceutical chemicals can also function as reversible or irreversible inhibitors of DMEs, which may also impact the pharmacokinetics and pharmacodynamics (PK/PD) of drugs. Therefore, we cannot simply conclude that the PXR-induced alteration in enzyme expression always reflects functional changes. We should consider both PXR activation and DMEs inhibition to improve drug safety in the clinic.

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“…Taesotikul et al [6] reported that ethanolic and aqueous extracts of Phyllanthus amarus inhibited CYP1A2, CYP2D6, CYP2E1 and CYP3A4 activity in a dose-dependent manner. Tanshinones of Salvia miltiorrhiza inhibit the metabolism of various cytochrome (CYP1A2, CYP2C9, CYP2E1, and CYP3A4) probe substrates in human liver microsomes and specific human CYP isoforms [7].…”

Section: Introductionmentioning

confidence: 99%

Effect of <b><i>Trigonella foenum-graecum</i></b> L. on Metabolic Activity of CYP2D6 and CYP3A4

et al. 2015

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Background: The present study investigated the effect of fenugreek seeds powder and its alcoholic extract on metabolic activity of drug-metabolizing enzymes CYP2D6 and CYP3A4. Materials and Methods: Dextromethorphan (DEX) was used as a probe for measuring metabolic activity, based on its CYP2D6- and CYP3A4-mediated metabolism to dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. For the in vitro investigations, DEX (25µM) was incubated with human liver microsomes and NADPH and tested with and without the fenugreek extract. For the in vivo study, phase I, 6 subjects received a single dose of DEX (30 mg); in phase II, after washout period, the fenugreek seeds powder was administered for 1 week and DEX was administered with its last dose. Results: In vitro, fenugreek extract inhibits CYP2D6-mediated O-demethylation of DEX. Higher concentrations (50 and 100µg/ml) of extract inhibit CYP2D6 and CYP3A4 activity. In vivo results indicated that fenugreek does not significantly inhibit CYP2D6 and CYP3A4 metabolic activity. There was no significant change in the levels of DEX metabolites (DOR 12% and 3-MM 9%) excreted in urine and their urine metabolic ratios (P values: 0.257 and 0.333 DEX/DOR and DEX/3-MM, respectively). Conclusion: In vitro and in vivo observations suggested that fenugreek may not have substantial effect on the metabolic activity of CYP2D6 and CYP3A4.

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Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro

Cited by 70 publications

References 39 publications

Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb–drug interactions

Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb–drug interactions

A Molecular Aspect in the Regulation of Drug Metabolism: Does PXR-Induced Enzyme Expression Always Lead to Functional Changes in Drug Metabolism?

Effect of <b><i>Trigonella foenum-graecum</i></b> L. on Metabolic Activity of CYP2D6 and CYP3A4

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