Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway
Parkinson’s disease (PD) is a common neurodegenerative disorder with no cure. Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity. The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A. membranaceus (TFA) and their p...
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Tsinghua University Press
2024-01-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023001210 |
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author | Zitian Gao Gaorui Wang Yujie Chen Wuke Yuan Jun Cai Aiping Feng Jie Fang Qi Xu Xiaojun Wu |
author_facet | Zitian Gao Gaorui Wang Yujie Chen Wuke Yuan Jun Cai Aiping Feng Jie Fang Qi Xu Xiaojun Wu |
author_sort | Zitian Gao |
collection | DOAJ |
description | Parkinson’s disease (PD) is a common neurodegenerative disorder with no cure. Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity. The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A. membranaceus (TFA) and their protective mechanisms. TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse model of Parkinsonism, by improving behavior performance in the gait analysis and pole test, and inhibiting the decline of tyrosine hydroxylase (TH) positive neurons and TH protein expression in substantia nigra of mice. TFA also prevented 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in SH-SY5Y cells, by increasing GSH and GSH/GSSG ratio, and reducing reactive oxygen species. In addition, the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+ induced downregulation of SLC7A11 and glutathione peroxidase 4 (GPX-4). In conclusion, we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+ induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis, suggesting the use of TFA as a possible food supplement in the prevention of PD. |
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language | English |
publishDate | 2024-01-01 |
publisher | Tsinghua University Press |
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spelling | doaj-art-8fb47790c9b8440c9b8098c66d5ce1b52025-02-03T06:57:18ZengTsinghua University PressFood Science and Human Wellness2213-45302024-01-01131414420Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathwayZitian Gao0Gaorui Wang1Yujie Chen2Wuke Yuan3Jun Cai4Aiping Feng5Jie Fang6Qi Xu7Xiaojun Wu8School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaLonghua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding authors.Parkinson’s disease (PD) is a common neurodegenerative disorder with no cure. Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity. The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A. membranaceus (TFA) and their protective mechanisms. TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse model of Parkinsonism, by improving behavior performance in the gait analysis and pole test, and inhibiting the decline of tyrosine hydroxylase (TH) positive neurons and TH protein expression in substantia nigra of mice. TFA also prevented 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in SH-SY5Y cells, by increasing GSH and GSH/GSSG ratio, and reducing reactive oxygen species. In addition, the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+ induced downregulation of SLC7A11 and glutathione peroxidase 4 (GPX-4). In conclusion, we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+ induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis, suggesting the use of TFA as a possible food supplement in the prevention of PD.http://www.sciencedirect.com/science/article/pii/S2213453023001210Parkinson’s diseaseTotal flavonoids of Astragalus membranaceusFerroptosisSLC7A11 |
spellingShingle | Zitian Gao Gaorui Wang Yujie Chen Wuke Yuan Jun Cai Aiping Feng Jie Fang Qi Xu Xiaojun Wu Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway Food Science and Human Wellness Parkinson’s disease Total flavonoids of Astragalus membranaceus Ferroptosis SLC7A11 |
title | Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway |
title_full | Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway |
title_fullStr | Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway |
title_full_unstemmed | Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway |
title_short | Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway |
title_sort | total flavonoids of astragalus membranaceus protect against 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine induced neurotoxicity in mice by inhibiting ferroptosis through slc7a11 gpx 4 signaling pathway |
topic | Parkinson’s disease Total flavonoids of Astragalus membranaceus Ferroptosis SLC7A11 |
url | http://www.sciencedirect.com/science/article/pii/S2213453023001210 |
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