Herbal supplement-based interactions

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.