Hepatotoxic assessment of Chelidonium majus L. and its alkaloids in primary hepatocyte cultures of different species

Herbal extracts of Chelidonium majus have been widely used in European countries and in Chinese herbal medicines for different applications, based on their anti-viral, anti-inflammatory and anti-microbial properties and their use against various liver disorders including cancer. Recently, several cases of liver disease have been related to C. majus intake. Therefore, we have used primary hepatocyte cultures of human, rat, canine and monkey to elucidate the potential hepatotoxicity of C. majus.

Water-soluble extracts were prepared and incubated with primary hepatocytes. Cellular viability and functions were analyzed by means of lactate dehydrogenase (LDH) and urea release and via the MTT assay. The amounts of different alkaloids present in C. majus extracts were determined by HPLC analysis.

The liquid extract showed a significant concentration-dependent toxicity in human hepatocytes and at concentrations of 7.5mg/ml for animal hepatocytes. In addition, C. majus lead to a decrease in urea release. The decline in urea production varied between the different species with regard to cellular sensitivity and to its maximal extent.

The data suggest that human hepatocytes seemed to be more sensitive to C. majus extracts than canine, rat and monkey hepatocytes, with rat hepatocytes being the most insensitive cells. In addition, these results demonstrate the necessity to use human hepatocytes in order to evaluate possible toxicological effects of complex plant extracts in humans.