2. Academic Validation
  3. Analysis of pyrrolizidine alkaloids in Eupatorium fortunei Turcz. and their in vitro neurotoxicity

Analysis of pyrrolizidine alkaloids in Eupatorium fortunei Turcz. and their in vitro neurotoxicity

  • Food Chem Toxicol. 2021 May;151:112151. doi: 10.1016/j.fct.2021.112151.
Yan Zhang 1,  Fei-Fei Yang 2,  Huan Chen 2,  Yao-Dong Qi 2,  Jian-Yong Si 2,  Qing Wu 3,  Yong-Hong Liao 4
Affiliations

Affiliations

  • 1 Beijing University of Chinese Medicine, Yangguang South Street, Fangshan District, Beijing, 102488, PR China; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, PR China.
  • 2 Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, PR China.
  • 3 Beijing University of Chinese Medicine, Yangguang South Street, Fangshan District, Beijing, 102488, PR China. Electronic address: qwu@vip.sina.com.
  • 4 Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, PR China. Electronic address: yhliao@implad.ac.cn.
PMID: 33774095 DOI: 10.1016/j.fct.2021.112151
Abstract

This study was to analyze the Pyrrolizidine Alkaloids (PAs) in Eupatorium fortunei herbs and its derived finished products with a view to evaluating their effects on the proliferation and oligodendrogenesis of neural progenitor cells (NPCs). Using a LC-MS/MS method with 32 PAs Reference Standards, 8 PAs including intermedine, intermedine N-oxide, lycopsamine, lycopsamine N-oxide, retronecine, seneciphylline and senkirkine and 7-acetylintermedine N-oxide were identified with intermedine N-oxide and lycopsamine N-oxide being most abundant. The total PA amounts were found to vary from 0.18 to 61.81 μg/g in 30 batches of herbs and from 0.86 to 36.96 μg/g in 4 commercial finished products, respectively. Risk assessments indicated that the short-term intake seemed unlikely lead to acute toxic effects but the chronic use warranted cautions. Using NPCs derived from mouse induced pluripotent stem cells as an in vitro testing model, intermedine, intermedine N-oxide and lycopsamine N-oxide appeared to decrease cell viability at 30 μM whereas intermedine N-oxide inhibited oligodendrogenesis of NPCs at 10 μM. The present results suggested that the PAs in the majority of E. fortunei herbs and the derived products not only resulted in their exposure far exceeding the acceptable intake limit (i. e. 1.0 μg PA per day for adults) in herbal medicinal products recommended by the European Medicines Agency but also induced neurotoxicity to NPCs in vitro.

Keywords

Eupatorium fortunei; Neural progenitor cells; Neurotoxicity; Oligodendrogenesis; Pyrrolizidine alkaloids.

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