Aristolochic Acids and Aristoloxazines Are Widespread in the Soil of Aristolochiaceae Herb Cultivation Fields

Abstract

The cancer risk associated with aristolochic acid (AA) exposure through the consumption of AA-containing herbal medicine has received tremendous attention in the past decades. However, environmental exposure routes from the associated medicinal herb cultivation fields have received little attention. We reveal through liquid chromatography-tandem mass spectrometry analysis of over 400 soil samples collected from three different Aristolochiaceae herb cultivation fields that AAs, which are nephrotoxic and carcinogenic, and aristoloxazines (AXs), a family of recently identified neurotoxic and genotoxic AA analogues, are widespread pollutants in these areas. In particular, aristoloxazine C was detected for the first time in the environment and was found in 318 out of 320 soil samples, at concentrations as high as 2.8 mg/kg, from an Asarum heterotropoides cultivation field. We show that in fact AXs are ecotoxic, inhibiting plant growth and significantly reducing the soil microorganism population. With the extensive cultivation of Aristolochiaceae herbs in order to meet their market demand, we believe our study points to an important environmental hazard that may place food crops and non-AA/AX-producing medicinal herbs at risk of AA/AX contamination. While previous research focused primarily on the health risks associated with exposure to AAs, this study uncovers environmental exposure as a new human exposure pathway that warrants the attention of both the general public and regulatory agencies.

Keywords: aristolochic acid; aristolochic acid nephropathy; aristoloxazine C; herbal medicines; terrestrial contaminants.