Toxicity Assessment of Nine Types of Decoction Pieces from the Daughter Root ofAconitum carmichaeli(Fuzi) Based on the Chemical Analysis of their Diester Diterpenoid Alkaloids

Abstract

Various processed types of FUZI (the daughter roots of the highly toxic plant Aconitum carmichaeli Debx, FZ) decoction pieces (the herbal materials processed according to the specifications of Chinese medicine manuals; " YINPIAN" in Chinese transliteration) are widely used in traditional medicine to treat various diseases, but their toxicities are not known. Nine types of FZ decoction pieces, including one raw slice and eight processed forms, were therefore prepared, each in 7 to 10 batches, to assess for their toxicity. Altogether 84 FZ samples were quantified on the amount of highly toxic diester diterpenoid alkaloids, i.e., aconitine, mesaconitine and hypaconitine by a newly developed HPLC method with HPLC-DAD and LC-MS techniques. The comparison of the processed FZ to raw slices of the root showed that the amount of each analyte in the processed FZ was drastically decreased. The sum of the three toxic compounds in the 8 types of processed FZ was only 3.91-34.80 % of this value in the FZ raw slice. This implies that the toxicity of processed FZ was decreased significantly. The amounts of toxic components in the 8 types of processed FZ varied significantly, often by a power of ten, indicating that the dosage of these herbs, when prescribed for clinical uses, should be cautiously set in order to avoid poisoning incidents.

Investigations of diterpene alkaloids isolated from Aconitum anthora L. and A. moldavicum L., and of aconitine-derived lipo-alkaloids

“…by a recent investigation on Radix aconiti lateralis preparata in which the sum of aconitine, mesaconitine and hypaconitine measured in 8 drug sample types was found to be 3.91-34.8% of that to be found in the corresponding crude drugs. 143 Nonetheless, this latest demonstration of significant variation in the toxic alkaloid contents is in line with practically all other previous studies conducted with the same purpose of DA content comparison in commercial TCM aconite samples. 4 However, it is interesting to note that there are several papers dealing with the detection of the toxic DA alkaloids aconitine, hypaconitine and mesaconitine in human body fluids (urine and blood/plasma samples) by different highly sensitive methods.…”

“…4 The number of victims of aconite poisonings 143 ; and unfortunately, the number of forensic case reports is constantly increasing. 48,[137][138][139][140][141][142] The main causes of death are refractory ventricular arrhythmias and asystole and the overall in-hospital mortality is 5.5%.…”

Case reports of aconite poisoning in mainland China from 2004 to 2015: A retrospective analysis

“…From 2001 to 2010, roughly 5000 cases of aconite poisoning were reported in China, Japan, Germany, and other countries [32].…”

Multi-composition analysis inRadix Aconiti Lateralisby single marker quantitation

“…Four major groups of alkaloids were found in the roots of Aconitum carmichaeli, which are monoester diterpene alkaloids (MDAs), amine diterpenoid alkaloids (ADAs), diester diterpene alkaloids (DDAs), and lipoalkaloids. The toxicity of Aconitum carmichaeli mainly derives from the DDAs, including aconitine, mesaconitine, and hypaconitine [5][6][7][8]. As we know, traditional Chinese medicine (TCM) herbal processing approaches, namely, "Paozhi," by means of the transformation of secondary plant metabolites, help to reduce the toxicity of the crude drug and might exert a large maximal therapeutic efficacy with minimal adverse effects.…”