粉防己与其主要组分粉防己碱效、毒作用及关系初探

Toxicity and Efficacy Research About Aqueous Extract of Stephania tetrandra and Tetrandrine

目的:结合粉防己碱在生药及水提物中含量的测定,从效、毒两个维度来阐释粉防己与其主要生物碱粉防己碱的作用差异及两者之间的关系。方法:HPLC测定粉防己水提物中粉防己碱的含量的基础上,确定粉防己碱给药剂量,分别采用热板法、小鼠耳肿胀法对粉防己与粉防己碱的镇痛、抗炎作用进行比较研究;同时,选取给药12,24 d以及停药12 d 3个不同时间点实验动物总蛋白(TP),白蛋白(ALB),丙氨酸氨基转氨酶(ALT),天冬氨酸氨基转氨酶(AST),总胆红素(TBIL)作为观测指标,对粉防己与粉防己碱的肝脏毒性进行探查和比较。结果:1防己药材中粉防己碱的含量8.99 mg·g-1,粉防己水提液中粉防己碱的转移率为30.03%;2粉防己与粉防己碱均有明显的镇痛作用,但从短期镇痛效果而言,以粉防己碱为佳,从长期镇痛效果而言,以粉防己水提物为佳。粉防己碱的抗炎效果相对优于粉防己水提物的抗炎效果,但两者相比无显著性差异。3粉防己水提物和粉防己碱给药均可以造成一定程度的肝细胞受损,但两者的作用机制不同,且粉防己水提物造成的肝脏损伤停药后具有可逆性,而粉防己碱造成的肝脏损伤在停药后则继续发展。结论:粉防己碱作为粉防己的主要组分,并不能够完全表征粉防己的药效及毒性,同样的,粉防己中的其他组分也对粉防己碱的毒性作用没有明显的监制作用。粉防己碱与粉防己的效、毒作用表现及机制并不相同。

Objective： Based on the detection of tetrandrine in aqueous extract of Stephania tetrandra, this study aired to elucidate the function discrepency of S. tetrandra and its main alkaloids-tetrandrinein effectiveness and toxicity, and to discover the relationship between them. Method： Tetrandrine content in the aqueous extract of S. tetrandra was determined by HPLC to define corresponding dose, then, analgesic and anti- inflammatory effects of tetrandrine and aqueous extract of S. tetrandra were studied by the method of hot plate and ear swelling in mice. Meanwhile, the contents of alanine transaminase （ALT） , aspartate transaminase （AST） , total protein （TP） , albumin （ALB） and total bilirubin （TBIL） in plasma of rats at the different time points drug treatment of 12 days, 24 days and 12 days after drug discontinuation were determined to detect the liver toxicity. Result： （1）The content of tetrandrine in S. tetrandra was 8.99 mg·g^-1, the transferring rate of tetrandrine was 30.03% in the aqueous extract of S. tetrandra. （2）Aqueous extract of S. tetrandra and tetrandrine both have obvious analgesic action, but as to the short-term analgesic effect, tetrandrine was better than aqueous extract of S. tetrandra, while as for the lone-term analgesic effect, aqueous extract of S. tetrandra was better than tetrandrine. Referring to the anti-inflammatory effect, tetrandrine was relatively better than aqueous extract of S. tetrandra, but there was no significant difference. （3） Both aqueous extract of S. tetrandraa and tetrandrine caused liver cell damage, but the mechanism was different. After drug discontinuation, the liver damage caused by aqueous extract of S. tetrandra was reversible while continuly deteriorated in the case of tetrandrine. Conclusion：As the major component of S. tetrandra, tetrandrine is not able to fully express the efficacy and toxicity of S. tetrandra, similarly, the other components of S. tetrandra could not prevent the toxic effects of tetrandrine. The function and mechanism are both different between the aqueous extract of S. tetrandra and tetrandrine.