Establishment of a bioassay for the toxicity evaluation and quality control of Aconitum herbs.

Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs.

[1]  C. Herzog,et al.  Bidirectional ventricular tachycardia resulting from herbal aconite poisoning. , 2005, Annals of emergency medicine.

[2]  Zhong-Zhen Zhao,et al.  Toxicity assessment of nine types of decoction pieces from the daughter root of Aconitum carmichaeli (Fuzi) based on the chemical analysis of their diester diterpenoid alkaloids. , 2010, Planta medica.

[3]  Thomas Y. K. Chan,et al.  Incidence of Herb-Induced Aconitine Poisoning in Hong Kong , 2002, Drug safety.

[4]  B. Wilffert,et al.  Mode of antinociceptive and toxic action of alkaloids of Aconitum spec. , 1997, Naunyn-Schmiedeberg's Archives of Pharmacology.

[5]  E. Randell,et al.  A Case of Fatal Aconitine Poisoning by Monkshood Ingestion * , 2008, Journal of forensic sciences.

[6]  W. Poon,et al.  Hidden aconite poisoning: identification of yunaconitine and related aconitum alkaloids in urine by liquid chromatography-tandem mass spectrometry. , 2006, Journal of Analytical Toxicology.

[7]  Jan van der Greef,et al.  Quality and safety of Chinese herbal medicines guided by a systems biology perspective. , 2009, Journal of ethnopharmacology.

[8]  Y. Dong,et al.  [Comparison of arrhythmic effects of aconitine and its 5 analogues (author's transl)]. , 2016, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[9]  T. Chan,et al.  Clinical features and management of herb-induced aconitine poisoning. , 2004, Annals of emergency medicine.

[10]  R. Bauer,et al.  Qualitative and quantitative analysis of aconitine-type and lipo-alkaloids of Aconitum carmichaelii roots. , 2009, Journal of chromatography. A.

[11]  Liang Liu,et al.  Quantification of Aconitum alkaloids in aconite roots by a modified RP-HPLC method. , 2005, Phytochemical analysis : PCA.

[12]  C. China Pharmacopoeia,et al.  Pharmacopoeia of the People's Republic of China , 2010 .

[13]  Juei-Tang Cheng,et al.  Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products. , 2005, Journal of ethnopharmacology.

[14]  Hideyuki Hayakawa,et al.  Effects of long-term administrations of aconitine on electrocardiogram and tissue concentrations of aconitine and its metabolites in mice. , 2005, Forensic science international.

[15]  J. Chan,et al.  Aconitine poisoning due to Chinese herbal medicines: a review. , 1994, Veterinary and human toxicology.

[16]  S. Kanba,et al.  Aconiti tuber increases plasma nitrite and nitrate levels in humans. , 2005, Journal of ethnopharmacology.

[17]  Ming Zhu,et al.  Aconitum in traditional Chinese medicine: a valuable drug or an unpredictable risk? , 2009, Journal of ethnopharmacology.

[18]  M. Wu,et al.  Toxicological mechanisms of Aconitum alkaloids. , 2006, Die Pharmazie.

[19]  Liang Liu,et al.  Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography. , 2005, Journal of chromatography. A.

[20]  C. Lai,et al.  Aconite poisoning in camouflage. , 2006, Hong Kong medical journal = Xianggang yi xue za zhi.

[21]  J. Hoogsteen,et al.  Salade malade: malignant ventricular arrhythmias due to an accidental intoxication with Aconitum napellus , 2008, Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation.

[22]  Maw-rong Lee,et al.  Determination of aconitine-type alkaloids as markers in fuzi (Aconitum carmichaeli) by LC/(+)ESI/MS(3). , 2008, Journal of pharmaceutical and biomedical analysis.

[23]  B. Wilffert,et al.  Aconitum sp. alkaloids: the modulation of voltage-dependent Na+ channels, toxicity and antinociceptive properties. , 1997, European journal of pharmacology.

[24]  Ckh Au,et al.  Three Cases of Aconite Root Poisoning Due to Bikhama in a Hong Kong Nepalese Family , 2010 .

[25]  S P Elliott,et al.  A case of fatal poisoning with the aconite plant: quantitative analysis in biological fluid. , 2002, Science & justice : journal of the Forensic Science Society.

[26]  A. Ameri The effects of Aconitum alkaloids on the central nervous system , 1998, Progress in Neurobiology.

[27]  R. Witkamp,et al.  Metabolomics in the context of systems biology: bridging traditional Chinese medicine and molecular pharmacology , 2005, Phytotherapy research : PTR.

[28]  N. Bisset Arrow poisons in China. Part II. Aconitum--botany, chemistry, and pharmacology. , 1981, Journal of ethnopharmacology.

[29]  Zhao Wang,et al.  Disruption of the intracellular Ca2+ homeostasis in the cardiac excitation-contraction coupling is a crucial mechanism of arrhythmic toxicity in aconitine-induced cardiomyocytes. , 2007, Biochemical and biophysical research communications.

[30]  T. Y. Chan Aconite poisoning , 2009, Clinical toxicology.