Search JIM Advanced Search

Journal of Integrative Medicine ›› 2023, Vol. 21 ›› Issue (3): 302-314.doi: 10.1016/j.joim.2023.04.001

• Original Experimental Research • Previous Articles    

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine

Yu-jie Wang a, Yan Wang b, Pei Tao b   

  1. a. School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China
    b. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China
  • Received:2022-02-25 Accepted:2022-06-27 Online:2023-05-15 Published:2023-05-15
  • Contact: Yu-jie Wang

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.

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.

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.

Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines.

Key words: 3-Acetylaconitine, Acute toxicity, Antiarrhythmic agents, 16-Epi-pyroacetylaconitine, Pyroacetylaconitine, Processing

[1] Ruo-lan Li, Qing Zhang, Jia Liu, Li-ying He, Qin-wan Huang, Wei Peng, Chun-jie Wu. Processing methods and mechanisms for alkaloid-rich Chinese herbal medicines: A review. Journal of Integrative Medicine, 2021, 19(2): 89-103.
[2] Sitthichai Iamsaard, Supatcharee Arun, Jaturon Burawat, Supataechasit Yannasithinon, Saranya Tongpan, Sudtida Bunsueb, Natthapol Lapyuneyong, Pannawat Choowong-in, Nareelak Tangsrisakda, Chadaporn Chaimontri, Wannisa Sukhorum. Evaluation of antioxidant capacity and reproductive toxicity of aqueous extract of Thai Mucuna pruriens seeds. Journal of Integrative Medicine, 2020, 18(3): 265-273.
[3] Jeremiah Oshiomame Unuofin, Gloria Aderonke Otunola, Anthony Jide Afolayan. Evaluation of acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. in Wistar rats. Journal of Integrative Medicine, 2018, 16(5): 335-341.
[4] Yin Fan Arthur, LixingLao, Rui-xin Zhang, An-nan Zhou, Brian M. Breman. Preclinical safety evaluation of the aqueous acetone extract of Chinese herbal formula Modified Huo Luo Xiao Ling Dan. Journal of Chinese Integrative Medicine, 2010, 8(5): 438-447.
[5] Chun-feng Chen, Yi-qin Wang, Jian-jun Yan, Yong Shen, Ling-yun Chen. Application of voice signal collection and analysis in traditional Chinese medicine syndrome differentiation of deficiency and excess. Journal of Chinese Integrative Medicine, 2010, 8(10): 944-948.
[6] Guo Li, De-feng Zhang, Run-min Ru, Wen-kai Wang. Review on the methods of processing rhubarb. Journal of Chinese Integrative Medicine, 2008, 6(11): 1184-1189.
[7] Bai Li, Li-feng Zhu, Ya-ni Zhang, Wei Gu. Comparison of acute toxicity of two preparations of norcantharidin in mice. Journal of Chinese Integrative Medicine, 2007, 5(1): 74-77.
[8] Feng-lan Zhu​, Chao Gu​, Zhi-feng Zhang​, Chang-le Zhou​, Jia-tuo Xu​, Xiao-gu Liu​, Wen-shu Li​, Hui-qing Zhu​. Evaluation of therapeutic effects of Chinese materia medica by tongue image analysis software 1.0 based on tongue colors. Journal of Chinese Integrative Medicine, 2006, 4(2): 152-155.
[9] Xiao-qiang Yue, Qing Liu. Analysis of studies on pattern recognition of tongue image in traditional Chinese medicine by computer technology. Journal of Chinese Integrative Medicine, 2004, 2(5): 326-329.
[10] Qing Liu, Xiao-qiang Yue, Rong-zheng Ren, Chuan-hong Ma, Chang-quan Ling. Characteristics of sublingual venae in primary liver cancer patients in different clinical stages. Journal of Chinese Integrative Medicine, 2004, 2(3): 175-177.
[11] Qing Liu, Xiao-qiang Yue, Wei-zhe Deng, Rong-zheng Ren, Chang-quan Ling. Quantitative study on tongue color in primary liver cancer patients by analysis system for comprehensive information of tongue diagnosis. Journal of Chinese Integrative Medicine, 2003, 1(3): 180-183.
Full text



No Suggested Reading articles found!