基于液质联用技术对大叶柴胡中多炔烯类化合物神经毒性的代谢组学研究

LC-MS based Metabolomics Study on Neurotoxicity of Polyacetylenes in Bupleurum Longiradiatum Turcz.

目的研究大叶柴胡中多炔烯类化合物的神经毒性机制,评价柴胡属植物的用药安全性。方法采用超高效液相色谱串联四级杆-飞行时间质谱技术并结合现代药理学的研究方法,对大叶柴胡中多炔烯类化合物给药后大鼠的脑脊液进行代谢组学研究,探讨多炔烯类化合物的可能毒性作用机制。结果结合模式识别和多元统计分析,最终共鉴定出4个潜在生物标志物,柴胡毒素给药组1-(3,4-二甲氧苯基)-1,2-乙二醇-1-氧基-b-D-糖苷和D(L)-鸟氨酸-L-丙氨酸的含量显著上升,3-氧代-3-脲基丙酸酯和辛胺含量显著下降,提示多炔烯类毒素可能作用于氧化应激与脂代谢通路继而引起毒性反应。结论本研究揭示了大叶柴胡中多炔烯类化合物神经毒性的潜在机制,为柴胡属及其他中药临床前毒性研究提供参考。

Objective To investigate the neurotoxic mechanism of polyacetylene compounds in Bupleurum longiradiatum Turcz.and evaluate the safety of Bupleurum as a drug.Methods Liquid chromatography-quadrupole-time of flight-mass spectrometry(LC-Q-TOF-MS)combined with modern pharmacological research methods was used to conduct metabolomics studies on the cerebrospinal fluid of rats administered with polyacetylene compounds in Bupleurum in order to explore the possible toxic mechanisms of polyacetylene compounds.Results The combination of pattern recognition with multivariate statistical analysis led to the identification of four potential biomarkers.The contents of 1-(3,4-dimethoxyphenyl)-1,2-ethanediol-1-o-beta-D-glucopyranoside and D(L)-ornithino-L-alanine increased significantly,while those of 3-oxo-3-ureido-propionic acid and octopamine decreased significantly in the experimental group,suggesting that polyacetylene toxins might act on oxidative stress and through lipid metabolism pathways,leading to toxic reactions.Conclusion This study has revealed the potential mechanism of neurotoxicity of polyacetylene compounds in Bupleurum,which can contribute to preclinical toxicity research on Bupleurum and other traditional Chinese medicines.