Zhang Ding-Kun, Han Xue, Tan Peng, Li Rui-Yu, Niu Ming, Zhang Cong-En, Wang Jia-Bo, Yang Ming, Xiao Xiao-He
Provincial and State Key Laboratory Breeding Base of System Research, Development and Utilization of Chinese Herbal Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China; Sichuan Good Doctor Panxi Pharmaceutical Co., Ltd., Xichang 610031, China.
Provincial and State Key Laboratory Breeding Base of System Research, Development and Utilization of Chinese Herbal Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing 100039, China.
Chin J Nat Med. 2017 Jan;15(1):49-61. doi: 10.1016/S1875-5364(17)30008-0.
Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.
附子是一种名贵药材，但也是有毒物质，需经过解毒处理后才能使用。传统炮制方法虽能达到预期解毒效果，但存在明显弊端，包括生物碱大量损失和质量一致性差。因此，有必要开发新的解毒方法。在本研究中，我们设计了一种通过快速干燥鲜切附子颗粒的新型一步解毒方法。为评估该技术优势，采用高效液相色谱法（HPLC）和超高效液相色谱/四极杆飞行时间质谱联用仪（UHPLC/Q-TOF-MS）测定了中乌头碱、乌头碱、次乌头碱、苯甲酰中乌头碱、苯甲酰乌头碱、苯甲酰次乌头碱、新乌头碱、伏毛铁棒锤碱、松果碱和塔拉地萨敏的含量。应用聚类分析和主成分分析等多变量分析方法来确定样品之间的质量差异。我们的结果表明，传统工艺虽能按预期降低毒性，但导致超过85.2%的生物碱损失。然而，我们的新型一步法能够达到几乎相同的解毒效果，生物碱损失仅约30%。聚类分析和主成分分析表明，生附片和新型产品与各种传统产品有显著差异。急性毒性试验表明，新型产品具有良好的解毒效果，其最大耐受剂量相当于成人用量的20倍。心脏效应试验也表明，新型产品的活性强于传统产品。此外，颗粒规格极大地提高了新型产品的质量一致性，大大优于传统产品。这些结果将有助于指导附子加工技术的合理优化，为临床治疗提供更好的药物。
