Establishment Of The Quality Assessment Model Of Aconitum Toxic Herbs Based On Bioassay

Aconitum herbs are widely used in traditional Chinese medicines (TCM). They have similar pharmacologic actions and are commonly applied for various diseases, such as collapse, syncope, rheumatic fever, painful joints, bronchial asthma, and various tumors. But there is a common characteristic for all Aconitum herbs. They are all highly toxic, and have a narrow margin of safety between a therapeutic and toxic dose. The cardiotoxicity and neurotoxicity of these herbs are potentially lethal, and the cases of poisoning and even death are usually reported owing to the improper use of Aconitum herbs in Asian countries. Therefore, the safety assessment is a top priority for the quality assessment of Aconitum herbs. However, the existing safety assessment methods and standards for Aconitum herbs can not meet the needs of clinical practice and production of traditional medicines. In order to make up for the shortages of the existing safety assessment methods, this study tried to establish the quality assessment model of Aconitum herbs based on bioassay to reduce the occurrence of aconite poisoning in clinic. The main results are summarized below:1. For the safety assessment of Aconitum herbs, a direct bioassay was designed for the first time to determine the toxic potency of Aconitum herbs by comparing the minimum lethal doses (MLD) of test sample in animals with that of standard.2. In order to improve the precision and reliability of the bioassay, the effects of experimental conditions were investigated with the MLD as target and finally the standardized bioassay was established based on the optimized experimental conditions. This method was simple and rapid with better repeatability, and required neither elaborate equipment nor special skills.3. UPLC method for the quantitative analysis of the three major toxic alkaloids (aconitine, mesaconitine and hypaconitine) in Aconitum herbs was established. The analysis speed was improved significantly compared with the common liquid chromatography method.4. The comparative analysis suggested that the bioassay as a new method offered unique advantages over the chemical analysis method. The chief advantage of the bioassay was that it could characterize the total toxicity of Aconitum herbs, resulting in more reliable safety assessment.5. Finally the quality assessment model of Aconitum herbs was developed, which was that the bioassay method and chemical analysis method were used together for the quality control of Aconitum herbs with the bioassay as chief method and the chemical analysis as accessorial method. In addition, the quality assessment standard, with the bioassay method as the core content and General-Chemical-Biological test as the whole method, were established preliminarily for the quality assessment of Aconitum herbs.According to above results, it can be concluded that the bioassay method established in this study was of advantage to the quality control of Aconitum herbs. And the development of the model for the quality assessment of Aconitum herbs offered a new way and technical support for the quality assessment of other toxic TCM.