Effects of dietary phenolics and botanical extracts on hepatotoxicity-related endpoints in human and rat hepatoma cells and statistical models for prediction of hepatotoxicity

Toxicity assessment of botanical materials is difficult because they are typically complex mixtures of phytochemicals. In the present study, 16 phenolics were tested in both human (HepG2/C3A) and rat (MH1C1) hepatoma cells using a battery of eight toxicity endpoints. Cluster analysis was used to group the phenolics into four clusters for each cell type. Comparison of overall and individual liver activity of phenolics on both human and rat hepatoma cell lines showed significant differences for some endpoints. However, the cluster membership was similar across both cell types with the majority of phenolics clustering with the solvent control group (cluster 1). Each cell type produced a cluster of compounds with reported in vivo liver toxicity (cluster 2). Five herbal extracts were prepared and then tested as above. Using the cluster model developed with the phenolics, in the HepG2/C3A cells green tea was assigned to cluster 2 and the remaining four extracts to cluster 1. In the MH1C1 cells, green tea and thyme were assigned to cluster 2, cinnamon to cluster 4, and juniper berry and peppermint to cluster 1. The data suggest that this in vitro model may be useful for identifying hepatotoxic phenolics and botanical preparations rich in phenolics.