Interaction of Herbal Constituents with Cytochrome P450 Enzymes

Abstract

This article provides a review of the many facets of interactions between herbal constituents and cytochrome P450 (CYP450) enzymes. While stressing potential drug—herb interactions, the article also reviews information about how CYP450 enzymes participate in activating (for better or for worse) botanical constituents, and suggests circumstances in which the individual expression of patients’ CYP450 enzymes can influence the activity of botanical medicines affected by these enzymes.

The article reviews the effect of Hypericum perforatum (St. John’s wort) and Citrus decumana (grapefruit) on CYP3A4, and the potential influence of this effect on the metabolism of certain drugs. The article discusses the toxic activation by CYP3A4 of unsaturated pyrrolizidine alkaloids from plants such as Symphytum officinale (comfrey) and of alkylbenzenes such as safrole from Sassafras spp. (sassafras) and Areca catechu (areca or betel nut), and estragole from Foeniculum vulgare (fennel), Pimpinella anisum (anise), Ocimum basilicum (basil), and Artemisia dracunculus (tarragon). The effects of piperine from Piper nigrum (black pepper) and Piper longum (long pepper) on CYP3A4, as well as its interactions with Curcuma longa (turmeric), are surveyed. The effect of cruciferous vegetables, including Nasturtium officinale (watercress), and their isothiocyanate constituents (sulforaphane, phenylethyl isothiocyanate [PEITC], and most notably indole-3-carbinole) with CYP1A1, 1A2, and 2E1 are discussed in the context of carcinogenesis, induction of beneficial estrogen metabolism, and the ways in which the individual patient’s glutathione enzyme systems can alter the efficacy of these vegetables and isothiocyanates. The pharmacokinetics of Artemisia annua (sweet Annie, qing hao) and artemisinin are discussed in light of CYP450 interactions. The article also presents minor relationships involving plants and plant constituents and CYP450 enzymes, such as that of grapefruit with CYP2A6, the activation of resveratrol to its more active metabolite piceatannol, and interactions of artemisinin and Ginkgo biloba with CYP2C19.