Metabonomic study on the toxicity of Hei-Shun-Pian, the processed lateral root of Aconitum carmichaelii Debx. (Ranunculaceae)

The purpose of this paper was to study the effects of Hei-Shun-Pian, the processed lateral root of Aconitum carmichaelii Debx. (Ranunculaceae), on the metabolic profile of rats, to discuss the mechanism of toxicology and to find out the potential biomarkers of the toxic effects. Twenty male Wistar rats were divided into four groups (n = 5) and each group were administered orally with the decoction of Hei-Shun-Pian (88.1 g/kg per day, 35.6 g/kg per day, 17.6 g/kg per day) or equal volume of drinking water respectively for 14 days. Urine of every 24-h and the plasma of the last day were collected for NMR experiments, and then analyzed by multivariate analysis methods. Decreases in urinary excretion of taurine and trimethylamine-N-oxide (TMAO) and increases in urinary levels of citrate, 2-oxoglutarate (2-OG), succinate and hippurate were observed in the high and medium dosed groups at the early stage of the dosing period. Taurine level increased at the later stage of the dosing period to the normal value, and then even to a value higher than that of the control group at the end of the experiment. No metabolic differences were observed between low dosed and control groups until the later stage of the dosing period when a slight increase in urinary taurine level was observed, suggesting a cumulative effect. These results suggest the toxic effect of Hei-Shun-Pian on rat heart in a dose dependent manner. (C) 2008 Elsevier Ireland Ltd. All rights reserved.