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Herbal Supplement-Based Interactions

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Enzyme- and Transporter-Based Drug-Drug Interactions

Abstract

As herbal supplements are purchased and used by more than 25% of the general population, herbal supplement-based interactions have become increasingly reported. The primary mechanism of herb–drug interactions is modulation of metabolizing enzymes and/or transporters. This chapter highlights the modulation effects of several top selling herbal supplements (St. John’s wort, garlic, ginseng, milk thistle, ginkgo, and others) and important herbal constituents (flavonoids and isothiocyanates) on metabolizing enzymes/transporters and the subsequent herb–drug interactions. Literature reports indicate that these herbal supplements/constituents modulate various phase I/II enzymes and/or transporters at both functional and expression levels and have an impact on the pharmacokinetics of co-administered drugs, which are mainly metabolized/transported by these enzymes/transporters. The alteration in enzyme/transporter function by an herbal product may vary markedly due to different manufacturers or lots of herbal products, doses, drug substrates, and experimental systems used to evaluate potential interactions. Many effects of herbal supplements/constituents on enzymes/transporters have been investigated only in vitro. Further in vivo animal studies and clinical trials need to be carried out to confirm these in vitro observations and determine the clinical relevance of herbal–drug interactions.

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Abbreviations

AhR:

aryl hydrocarbon receptor

BITC:

benzyl isothiocyanate

BCRP:

breast cancer resistance protein

CAR:

constitutive androstane receptor

CYP:

cytochrome P450

DNM:

daunomycin

ECG:

epicatechin gallate

EGCG:

epigallocatechin gallate

GBE:

Ginkgo biloba extract

GSH:

glutathione

GST:

glutathione S-transferase

INR:

International Normalized Ratio

ITC:

isothiocyanates

MCT:

monocarboxylic transporter

MRP:

multidrug resistance protein

Nrf2:

E2-related factor2

OATP:

organic anion-transporting polypeptide

OSCs:

organosulfur compounds

PEITC:

phenethyl isothiocyanate

P-gp:

P-glycoprotein

PXR:

pregnane X receptor

QR:

quinone reductase

SFN:

sulforaphane

SJW:

St. John’s wort

SULT:

sulfotransferase

UGT:

UDP-glucuronosyltransferase

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Acknowledgments

Funding by the Susan G. Komen Foundation BCTR138506 and NIH grants R01DA023223 and R03CA121404 is acknowledged.

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  1. Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY, USA

    Guohua An

  2. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY, USA

    Marilyn E. Morris

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  1. Leslie Dan Fac. Pharmacy, University of Toronto, College Street 144, Toronto, M5S 3M2, Canada

    K. Sandy Pang

  2. Bristol-Myers Squibb Company, Princeton, 08543, U.S.A.

    A. David Rodrigues

  3. AstraZeneca UK, Alderley Park, Macclesfield, Cheshire, SK10 4TF, United Kingdom

    Raimund M. Peter

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An, G., Morris, M.E. (2010). Herbal Supplement-Based Interactions. In: Pang , K., Rodrigues, A., Peter, R. (eds) Enzyme- and Transporter-Based Drug-Drug Interactions. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0840-7_22

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