Bioactivation of herbal constituents: simple alerts in the complex system.

INTRODUCTION: The elucidation of the toxicological mechanisms of herbal medicines is becoming more and more important with the increasing application of herbal medicines, for treatment of various diseases and the promotion of health. Furthermore, it is widely recognized that as herbal components undergo bioactivation, there is a critical need for a greater understanding of herbal toxicity induction. AREAS COVERED: This article summarizes the current understanding of structural alerts present in herbal remedies as well as the herbs' and individuals' factors, complicating the interpretation of herbal toxicity via bioactivation. Medline (by means of PubMed up to July 2010) has been searched using proper relevant terms. The reader is provided with reported examples of herbal bioactivation based on toxicophores, which are summarized in an extended list. The article also discusses the factors which influence the herbal bioactivation study, including herbal complexity, competitive detoxification metabolism pathways as well as the individual and species difference of drug metabolizing enzymes and intestinal factors. EXPERT OPINION: The early evaluation of the bioactivation potential of herbal components is helpful for providing alerts of herbal toxicity. However, the potential toxic effects should be considered in the context of the complex systems of herbs and the individual patient.