制黄草乌中滇乌碱及其转化产物8-去乙酰基滇乌头碱药效和毒性的初步研究

A Preliminary Research on the Efficacy and Toxicity of Yunaconitine and 8-deacetylyunaconitine Isolated from the Processed Products of Aconiti Knsnezoffii Radix

目的对比研究滇乌碱及其转化产物8-去乙酰基滇乌头碱的镇痛抗炎作用及急性毒性。方法采用热板致小鼠疼痛模型和醋酸致小鼠扭体模型观察二者的镇痛作用,采用二甲苯致小鼠耳肿胀模型观察其抗炎作用;采用Bliss法测定其半数致死量。结果滇乌碱和8-去乙酰基滇乌头碱对热致痛有镇痛作用趋势,但差异均无统计学意义;对醋酸引起的疼痛均有明显的镇痛作用,滇乌碱高、低剂量均能显著降低小鼠扭体次数和延长小鼠疼痛潜伏期,8-去乙酰基滇乌头碱仅在高剂量时作用较显著;二者对二甲苯致小鼠耳廓肿胀的抑制作用与溶媒组比较差异不明显,抗炎作用不确切。滇乌碱的毒性是其转化产物8-去乙酰基滇乌头碱的近20倍。结论制黄草乌中滇乌碱及其转化产物8-去乙酰基滇乌头碱应为外周镇痛作用药物,其中8-去乙酰基滇乌头碱的毒性较小,且对醋酸引起的小鼠疼痛作用显著,安全性高。

Objective To conduct comparative study on the analgesic and anti-inflammatory effects as well as the acute toxicity of yunaconitine and 8-deacetyl-yunaconitine isolated from the processed products of Aconiti Knsnezoffii Radix. Methods The methods of hot plate test and writhing test were used to evaluate the analgesic effect. Anti-inflammation action was observed by the models of auricle swelling caused by dimethylbenzene. LD50 was determined by the method of Bliss. Results Yunaconitine and 8-deacetyl-yunaconitine have analgesia effect on the pain caused by hot-plate, but there were no statistically significant difference. The pain caused by acetic acid had obvious analgesic action. High and low dose of yunaconitine could significantly reduce the number of mice body torsion and extend the incubation period of pain in mice. The effect of 8-deacetyl-yunaconitine was remarkable only in the high dose. Compared with solvent group, there were little differences in inhibiting effect of auricle swelling caused by dimethylbenzene, and anti-inflammatory action was not exact. The poisonousness of yunaconitine was nearly 20 times of 8-deacetyl-yunaconitine. Conclusion Yunaconitine and 8-deacetyl-yunaconitine may be the analgesic medicine for peripheral analgesic effect. The poisonousness of 8-deacetyl-yunaconitine is less than yunaconitine, the effect is remarkable to the pain caused by acetic acid, and the security is high.