Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry

Yingrui Zhang; Shiyu Chen; Fangfang Fan; Ning Xu; Xian-Li Meng; Yi Zhang; Jin-Ming Lin

doi:10.1016/j.jpha.2022.11.007

Volume 13 Issue 1

Jan. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(1): 88-98

Yingrui Zhang, Shiyu Chen, Fangfang Fan, Ning Xu, Xian-Li Meng, Yi Zhang, Jin-Ming Lin. Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry[J]. Journal of Pharmaceutical Analysis, 2023, 13(1): 88-98. doi: 10.1016/j.jpha.2022.11.007

Citation:

Yingrui Zhang, Shiyu Chen, Fangfang Fan, Ning Xu, Xian-Li Meng, Yi Zhang, Jin-Ming Lin. Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry[J]. Journal of Pharmaceutical Analysis, 2023, 13(1): 88-98. doi: 10.1016/j.jpha.2022.11.007

Citation:

Yingrui Zhang, Shiyu Chen, Fangfang Fan, Ning Xu, Xian-Li Meng, Yi Zhang, Jin-Ming Lin. Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry[J]. Journal of Pharmaceutical Analysis, 2023, 13(1): 88-98. doi: 10.1016/j.jpha.2022.11.007

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Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry

doi: 10.1016/j.jpha.2022.11.007

a. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China;
b. Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing, 100084, China;
c. Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

Funds:

This research was supported the National Natural Science Foundation of China (Grant Nos.: 81973569, 82130113, and 22034005), the National Key R&

D Program of China (Grant No.: 2021YFF0600700), and the “Xinglin Scholars” Research Promotion Program of Chengdu University of Traditional Chinese Medicine (Grant No.: BSH2021009).

Received Date: Sep. 27, 2022
Accepted Date: Nov. 21, 2022
Rev Recd Date: Nov. 19, 2022
Publish Date: Nov. 23, 2022

Abstract

Abstract

Aconitine, a common and main toxic component of Aconitum, is toxic to the central nervous system. However, the mechanism of aconitine neurotoxicity is not yet clear. In this work, we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine. HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system. Meanwhile, to confirm the metabolic mechanism of aconitine toxicity on HT22 cells, the levels of lactate dehydrogenase, intracellular Ca²⁺, reactive oxygen species, glutathione and superoxide dismutase, and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology. Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid, which was followed by the accumulation of lactic acid and reduction of glucose. The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca²⁺ overload and oxidative stress, and eventually result in cell apoptosis. In general, we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.
- Aconitine,
- Neurotoxicity mechanism,
- HT22 cells,
- Excitatory amino acids,
- Microfluidic chip-mass spectrometry

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References(42)

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