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.
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.
Food Chem Toxicol. 2021 May;151:112151. doi: 10.1016/j.fct.2021.112151. Epub 2021 Mar 25.
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.
本研究旨在分析佩兰药材及其衍生制品中的吡咯里西啶生物碱（PAs），以评估其对神经祖细胞（NPCs）增殖和少突胶质细胞发生的影响。采用LC-MS/MS 法结合 32 种 PAs 对照品，鉴定出 8 种 PAs，包括 Intermedine、Intermedine N-氧化物、Lycopsamine、Lycopsamine N-氧化物、Retronecine、Seneciphylline 和 Senkirkine 以及 7-Acetylintermedine N-氧化物，其中以 Intermedine N-氧化物和 Lycopsamine N-氧化物含量最高。在 30 批药材中，总 PA 含量范围为 0.18-61.81μg/g，4 种商业成品中总 PA 含量范围为 0.86-36.96μg/g。风险评估表明，短期内摄入不太可能导致急性毒性作用，但长期使用需要谨慎。以诱导多能干细胞分化的 NPCs 作为体外检测模型，结果显示 30μM 的 Intermedine、Intermedine N-氧化物和 Lycopsamine N-氧化物会降低细胞活力，而 10μM 的 Intermedine N-氧化物会抑制 NPCs 的少突胶质细胞发生。本研究结果表明，佩兰药材及其衍生制品中的 PAs 不仅导致其暴露量远远超过欧洲药品管理局推荐的草药药品中可接受的摄入量限值（即 1.0μg 每日每成人），而且还会导致 NPCs 发生体外神经毒性。
