Evaluation of the cytotoxicity and genotoxicity of aristolochic acid I - a component of Aristolochiaceae plant extracts used in homeopathy.

The medicinal plants Aristolochia clematitis L. as well as Asarum europaeum L., representatives of the plant family Aristolochiaceae and mentioned in the German Homeopathic Pharmacopeia, contain aristolochic acid. We found that the mother tinctures of A. clematitis and A. europaeum inhibited DNA synthesis in human hepatoma HepG2 cells in a dose-dependent manner. One of the components of the plant extract, aristolochic acid I (AAI), is linked to the development of nephropathy and urothelial cancer in humans. Therefore, we also evaluated the cytotoxicity and genotoxicity of AAI in HepG2 cells. Cell proliferation was inhibited concentration-dependently by AAI using BrdU-ELISA and colony forming assay. AAI formed DNA adducts (measured by (32)P-postlabeling), induced chromosomal aberrations (micronuclei) and DNA strand breaks. DNA damage induced by AAI led to an arrest of cells in the S-phase which was associated with the increased expression of p53 and p21 proteins. The results are discussed under consideration of former studies.