Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry
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 n...
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| Format: | Article |
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Elsevier
2023-01-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177922001204 |
| _version_ | 1797938106337329152 |
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| author | Yingrui Zhang Shiyu Chen Fangfang Fan Ning Xu Xian-Li Meng Yi Zhang Jin-Ming Lin |
| author_facet | Yingrui Zhang Shiyu Chen Fangfang Fan Ning Xu Xian-Li Meng Yi Zhang Jin-Ming Lin |
| author_sort | Yingrui Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T18:54:30Z |
| format | Article |
| id | doaj.art-471492e8fca94c8185da7e0ba4f37390 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-04-10T18:54:30Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-471492e8fca94c8185da7e0ba4f373902023-02-01T04:25:43ZengElsevierJournal of Pharmaceutical Analysis2095-17792023-01-011318898Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometryYingrui Zhang0Shiyu Chen1Fangfang Fan2Ning Xu3Xian-Li Meng4Yi Zhang5Jin-Ming Lin6State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing, 100084, ChinaEthnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, ChinaBeijing Key Laboratory of Microanalytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing, 100084, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, ChinaEthnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; Corresponding author.Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Department of Chemistry, Tsinghua University, Beijing, 100084, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2095177922001204AconitineNeurotoxicity mechanismHT22 cellsExcitatory amino acidsMicrofluidic chip-mass spectrometry |
| spellingShingle | 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 Journal of Pharmaceutical Analysis Aconitine Neurotoxicity mechanism HT22 cells Excitatory amino acids Microfluidic chip-mass spectrometry |
| title | Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry |
| title_full | Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry |
| title_fullStr | Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry |
| title_full_unstemmed | Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry |
| title_short | Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry |
| title_sort | neurotoxicity mechanism of aconitine in ht22 cells studied by microfluidic chip mass spectrometry |
| topic | Aconitine Neurotoxicity mechanism HT22 cells Excitatory amino acids Microfluidic chip-mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S2095177922001204 |
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