Toxicological risk assessment of Aristolochia species

Aristolochia species are known to contain aristolochic acids, nitrophenantrene derivatives responsible for their nephrotoxic and genotoxic effects [1]. There are numerous aristolochic acid analogues, including aristolactams, a group of compounds with even higher cytotoxic potency than aristolochic acid I [2]. Previous research mainly focused on Aristolochia species used in traditional Chinese medicine, but ethnopharmacological studies indicate that other members of the genus are frequently used medicinally [3]. The aim of our research is to assess the toxicological risk associated with the use of different Aristolochia species as herbal medicines. Metabolomic analysis allows us to take into account all compounds that might be responsible for the nephrotoxic effect. LC-DAD-MS analysis was carried out on A. manshuriensis Kom., A. kankauensis Sasaki, A. clematitis L., A. elegans Mast., A. baetica L., A. debilis Siebold & Zucc. and related species and AA I, AA II, AL I and AA C were quantified. A. kankauensis contained the highest levels of AA I and AA II, whereas A. manshuriensis contained the largest variety of different AA analogues (AA I, AA II, AA C, AA D, AA C-β-D-glucoside and AA D-β-D-glucoside). The results show that the content of aristolochic acid analogues varies greatly between different parts of the plant, with highest amounts found in the flowers. Extraction of the plant material with aqueous ethanol results in high yields of AA I and AL I, whereas extraction with hot water only yields in small amounts of AA I and AL I, and can therefore be associated with lower toxicological risk.