Study on the acute neurotoxicity of Aconite in mice

Abstract: Objective To study the acute toxicity of salt aconite (SAC) on the nervous system of mice. Methods The spontaneous activity, climbing rod and Morris water maze test were used in the mice. The SAC crude drug 7.68, 3.84, 1.92g·kg ^-1 group was administered, ig was administered, and the negative control and positive control group were set. The number of spontaneous activities of the mice in 10 min was measured by spontaneous activity meter at 15 and 60 min after single administration. After 30 min of single administration, the mice were placed on the glass rod of the climbing frame, and the crawling time of the mice was recorded. The drug was administered for 4 days, and the water maze test was performed 30 minutes after the last administration, and the time when the mouse found the hidden platform was the escape latency. Results There were no significant differences in the number of spontaneous activities, climbing time and escape latency between the high, medium and low dose groups of the SAC group (P>0.05). Conclusion When SAC concentrations were 7.68, 3.84, 1.92g·kg ^-1 , no acute toxic effects on the nervous system of mice were observed.

Key words: salt aconite; number of spontaneous activities; climbing time; escape latency; neurotoxicity

Aconite Aconitumcarmichaeli is a processed product of the Aconite root of the Ranunculaceae plant, named after its epiphytic aconite. The toxic component of aconite is aconitine, soluble in water and ethanol, and is extremely toxic. People can take 0.22mg orally to produce symptoms of poisoning, and its crystallized 2~4mg can cause death. The salt aconite is made from the muddy immersion of Danba liquid and dried by air drying. It is a kind of artefact used in clinical practice. To provide a basis for its clinical safe drug use, the mouse spontaneous activity test, climbing rod test, Morris water maze test were used to study the acute neurotoxicity of salt aconite.

1 Experimental part

111 Test drugs, instruments and animals

Salt aconite (SAC, crude drug 1.09 g·ml ^-1 ) is a dark brown liquid, which is processed by salt-dip processing of mud aconite; diazepam injection (Tianjin Jinyao Amino Acid Co., Ltd., 5mg·ml ^-1 ); hydrogen Scopolamine bromide injection (Shanghai Hefeng Pharmaceutical Co., Ltd., 0.3 mg·ml ^-1 ). JXDH-I spontaneous activity instrument (Hebei Haoxing Test Instrument Company); Morris water maze system (Beijing Xintiandi Technology Co., Ltd.); mouse climbing frame (homemade). Ordinary healthy adult Kunming mice [Sichuan Experimental Animals Special Committee Farm, Production License No. SCXK (Chuan) 2004-014] a total of 150, weighing 20 to 26g, both use. The mice were housed in a small common animal room in the center, 5 per cage, temperature 20 ° C to 26 ° C, humidity 55% ± 15%, illumination time 12h / 12h. The mice were randomly divided into a negative control group, a positive control group, and a high, medium, and low dose group of aconite.

112 statistical methods

The results were expressed as x±s, and each group of data was analyzed by SPSS11.0 statistical software for one-way analysis of variance.

1. 3 Methods and results

A total of 50 spontaneously tested mice were randomly divided into 5 groups. The rats in the high, middle and low dose groups of SAC were given distilled water in the negative control group of 7168, 3184 and 1192g·kg ^-1 , respectively; the positive control group was given diazepam injection 5mg·kg ^-1 . The number of spontaneous activities in mice within 10 min was measured at 15 and 60 min after administration [1]. The results in Table 1 showed that there was no significant difference in the number of spontaneous activities between the SAC high, medium and low dose groups and the corresponding negative control group (P>0.05). The SAC high-dose group was compared with the middle and low-dose groups, but the difference was not statistically significant. 11312 The climbing rod experiment was grouped and administered according to the method of “1.3.1”. The mice were trained for two days before the test to learn to climb the rod. After 30 minutes of administration, the mice were placed on the glass rod of the climbing frame to make the muscles in a static state, and the time when the mice fell from the stick due to muscle fatigue was recorded, and the total climbing time was 3 times as the total climbing. Rod time. There was no significant difference in the climbing time between the SAC high, medium and low dose groups and the corresponding negative control group (P>0.05). The SAC high-dose group was compared with the middle and low-dose groups, but the difference was not statistically significant.

The 11313 Morris water maze test divides the Morris water maze into four quadrants, with the first quadrant of the platform about 1 cm from the water surface. The mice were first placed on the platform to familiarize them with the platform for 30 s, and then the mice were placed into the maze from the quadrant wall opposite to the platform, and the time for the mice to find the hidden platform was to escape the incubation period. If the platform is still not found in the 120 s mouse, the mouse is directed to the platform and the escape latency is counted as 120 s. The measurement was repeated once and the average value was taken. Except for the positive control group ip scopolamine hydrobromide injection 3mg·kg ^-1 , the other groups were grouped and administered according to the method of “1.3.1”, and each group was administered continuously for 4 days. The water maze test was performed 30 minutes after each administration, and the result of the fourth day was the official test result. The results showed that there was no significant difference in the escape latency between the SAC high, medium and low dose groups and the corresponding negative control group (P>0.05).

2 Discussion

Aconite has strong heart, anti-inflammatory, analgesic, anti-tumor, immune function, but it is also one of the common toxic Chinese medicines. Its main toxic component is a fat-soluble dilipid alkaloid, which is characterized by severe damage to the nervous and cardiovascular systems. Yanfuzi, Heshun tablets and Baifu tablets are the artillery products commonly used in clinical aconite. Among them, salt aconite is the most commonly used. Therefore, salt aconite is used to study its acute neurotoxicity. The salt aconite is a crude processed product of aconite. Its toxicity and pharmacological effects are not changed much compared with the aconite. Therefore, the experimental results also reflect the acute neurotoxicity of the aconite. The experiment used a combination of neurobehavioral tests to study the effects of salt aconite on neurobehavioral function in mice. There was no significant difference between the drug-administered group and the negative control group. However, the number of spontaneous activities and the time of climbing in the high-dose group of Yanfuzi were decreased compared with other groups, and the difference was not statistically significant. The possible reason is that the acute neurotoxicity of the salt aconite is low, and the short-term administration has little effect on the number of spontaneous activities and the climbing time of the mice, so the toxicity is less at a higher dose. The results showed that the acute toxic effects on the nervous system of mice were not observed when the concentration of crude aconite was 7168, 3184, and 1192 g·kg ^-1 .