Investigation of cytochrome P450-mediated toxicity of extracts of Polygonum multiflorum and Chelidonium majus

Botanical dietary supplements are commonly used throughout the world, and adverse hepatic reactions have been reported following their intake. In several cases, hepatic toxicity of botanical dietary supplements is the result of cytochrome P450 (CYP450) – mediated mechanisms leading to the formation of reactive metabolites (herbal bioactivation). These reactive metabolites covalently bind to cellular macromolecules such as DNA and protein, leading to toxicity via multiple mechanisms. In our investigation, metabolism-mediated toxicity of extracts of Polygonum multiflorum, Chelidonium majus and Symphytum spp. was studied using an in vitro assay. Human hepatocarcinoma (HepG2) cells were incubated with plant extracts in the presence and absence of an external metabolizing system (rat liver S9 fraction and NADPH) for 6h and the cytotoxicity was assessed as lowered mitochondrial activity (reduction of MTT). The potential reactive metabolites formed during the incubation will be identified by using mass spectrometric methods.