Objective:The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified.This study investigated the structural changes that ...Objective:The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified.This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.Methods:The diterpenoid alkaloid 3-acetylaconitine was heated at 180°C for 15 min to simulate the process of sand frying.The pyrolysis products were separated using column chromatography,and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy.Further,in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared,and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.Results:Two new diterpenoid alkaloids,pyroacetylaconitine and 16-epi-pyroacetylaconitine,a pair of epimers at C-16,were isolated.After comparing the structures of these compounds,possible transformation pathways were proposed.Compared with the prototype compound,3-acetylaconitine,the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased.In the biological activity assay,the two pyrolysis products exhibited an effective increase in ventricular premature beat latency,a reduction in the occurrence of ventricular tachycardia,as well as an increase in the rate of arrhythmia inhibition,implying strong antiarrhythmic activity.Conclusion:Compared with 3-acetylaconitine,its pyrolysis products displayed lower toxicity and good antiarrhythmic effects;thus,they have potential for being developed into antiarrhythmic medicines.展开更多
基金supported by the National Natural Science Foundation of China(No.81403104)the Sichuan Science and Technology Program(No.2020YJ0131)Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine,China(No.QNXZ2018042,No.QJRC2022046).
文摘Objective:The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified.This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.Methods:The diterpenoid alkaloid 3-acetylaconitine was heated at 180°C for 15 min to simulate the process of sand frying.The pyrolysis products were separated using column chromatography,and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy.Further,in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared,and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.Results:Two new diterpenoid alkaloids,pyroacetylaconitine and 16-epi-pyroacetylaconitine,a pair of epimers at C-16,were isolated.After comparing the structures of these compounds,possible transformation pathways were proposed.Compared with the prototype compound,3-acetylaconitine,the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased.In the biological activity assay,the two pyrolysis products exhibited an effective increase in ventricular premature beat latency,a reduction in the occurrence of ventricular tachycardia,as well as an increase in the rate of arrhythmia inhibition,implying strong antiarrhythmic activity.Conclusion:Compared with 3-acetylaconitine,its pyrolysis products displayed lower toxicity and good antiarrhythmic effects;thus,they have potential for being developed into antiarrhythmic medicines.
