短柄乌头砂炒工艺优化及其急性毒性、抗心律失常活性研究  

Optimization of stir-frying with sand process for Aconitum brachypodum and its acute toxicity,anti-arrhythmic activity

作　　者：刘丛改 郑清洋 陈佳佳 王毓杰[1] LIU Cong-gai;ZHENG Qing-yang;CHEN Jia-jia;WANG Yu-jie(Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学,四川成都611137

出　　处：《中成药》2024年第12期3938-3945,共8页Chinese Traditional Patent Medicine

基　　金：四川省自然科学基金项目(2024NSFSC0702);四川省中医药管理局科学技术研究专项课题(2024MS178);成都中医药大学“杏林学者”学科人才科研提升计划(QJRC2022046)。

摘　　要：目的优化短柄乌头砂炒工艺,并考察其急性毒性、抗心律失常活性。方法以炒制温度、炒制时间、药砂比为影响因素,双酯型生物碱(乌头碱、滇乌碱)、单酯型生物碱(苯甲酰乌头原碱、16-epi-pyroaconitine、8-去乙酰滇乌碱和pyroyunaconitine)总含量的综合评分为评价指标,Box-Behnken响应面法优化砂炒工艺。采用急性毒性实验,计算生品、砂炒品LD_(50)。建立大鼠心律失常模型,测定室性早搏潜伏期、室性心动过速发生率。结果最优条件为炒制温度210℃,炒制时间15 min,药砂比1∶15,综合评分为93.932分。生品、砂炒品LD50分别为0.076、0.799 g/kg。与模型组比较,不同剂量(5、8、12、16 mg/kg)砂炒品组室性早搏潜伏期延长(P<0.05);与5 mg/kg剂量组比较,12~16 mg/kg剂量组室性心动过速发生率降低(P<0.05)。结论砂炒后短柄乌头急性毒性降低,并且在高剂量下表现出较强的抗心律失常活性。AIM To optimize the stir-frying with sand process forAconitum brachypodumDiels.,and to investigate its acute toxicity,anti-arrhythmic activity.METHODS With frying temperature,frying time and drug-sand ratio as influencing factors,comprehensive score for total contents of diester alkaloids( aconitine,yunaconitine) and monoester alkaloids( benzoylaconitine,16-epi-pyroaconitine,8-deacetylyunaconitine,pyroyunaconitine) as evaluation indices,the stir-frying with sand process was optimized by Box-Behnken response surface method.Acute toxicity test was adopted in the calculation of LD50of raw product and stir-frying with sandprocessed product.The model for rat arrhythmia was established,after which ventricular premature beat latency and incidence of ventricular tachycardia were determined.RESULTS The optimal conditions were determined to be210 ℃ for frying temperature,15 min for frying time was,and 1 ∶ 15 for drug-sand ratio,the comprehensive score was 93.932.The LD_(50) of raw product,stir-frying with sand-processed product were 0.076,0.799 g/kg,respectively.Compared with the model group,different doses(5,8,12,16 mg/kg) of stir-frying with sandprocessed product groups demonstrated prolonged ventricular premature beat latencies(P<0.05).Compared with the 5 mg/kg dose group,the 12-16 mg/kg dose group displayed decreased incidence of ventricular tachycardia(P<0.05).CONCLUSION Reduced acute toxicity ofA.brachypodumis observable after stir-frying with sand,which exhibits strong anti-arrhythmic activity at high dose.

关 键 词：短柄乌头 砂炒工艺 急性毒性 抗心律失常活性 Box-Behnken响应面法 

分 类 号：R283[医药卫生—中药学]