Liu Min, Cao Yan, Lv Diya, Zhang Wen, Zhu Zhenyu, Zhang Hai, Chai Yifeng
Department of Pharmacy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
J Pharm Anal. 2017 Jun;7(3):170-175. doi: 10.1016/j.jpha.2017.01.001. Epub 2017 Jan 7.
According to the Chinese Pharmacopoeia 2015, only processed tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in tubers. First, the chemical ingredients in unprocessed and processed tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids, monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats were used for validate the effect of processing on cardiac functions. After processing the tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diester-diterpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids. Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.
根据《中国药典》2015年版，仅炮制后的块茎可临床应用，且炮制效果尚不明确。本研究旨在探讨炮制对块茎中生物碱心脏功效的影响。首先，采用高效液相色谱-飞行时间质谱联用仪（HPLC-TOF/MS）及多元模式识别方法对未炮制和炮制后的块茎中的化学成分进行鉴定和比较。然后，选取块茎中分别属于二酯型二萜生物碱、单酯型二萜生物碱和胺型二萜生物碱的代表性生物碱乌头碱、苯甲酰乌头碱和乌头原碱，进一步验证炮制减毒机制。随后，在SD大鼠中进行乌头碱、苯甲酰乌头碱和乌头原碱的药理实验，以验证炮制对心脏功能的影响。对块茎进行炮制后发现，二酯型二萜生物碱含量降低，单酯型二萜生物碱和胺型二萜生物碱含量增加，表明二酯型二萜生物碱转化为单酯型二萜生物碱和胺型二萜生物碱。通过进一步将乌头碱在沸水中煎煮，证实这三种生物碱可逐步转化。在SD大鼠中进行的乌头碱、苯甲酰乌头碱和乌头原碱的药理实验表明，0.01mg/kg剂量的乌头碱和10mg/kg剂量的乌头原碱增强心脏功能，而2mg/kg剂量的苯甲酰乌头碱则减弱心脏功能。炮制的效果归因于毒性最强的二酯型二萜生物碱转化为毒性较小的单酯型二萜生物碱和胺型二萜生物碱。
