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...

Full description

Saved in:
Bibliographic Details
Main Authors: Zitian Gao, Gaorui Wang, Yujie Chen, Wuke Yuan, Jun Cai, Aiping Feng, Jie Fang, Qi Xu, Xiaojun Wu
Format: Article
Language:English
Published: Tsinghua University Press 2024-01-01
Series:Food Science and Human Wellness
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213453023001210
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832546410559438848
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.
format Article
id doaj-art-8fb47790c9b8440c9b8098c66d5ce1b5
institution Kabale University
issn 2213-4530
language English
publishDate 2024-01-01
publisher Tsinghua University Press
record_format Article
series Food Science and Human Wellness
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
work_keys_str_mv AT zitiangao totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT gaoruiwang totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT yujiechen totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT wukeyuan totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT juncai totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT aipingfeng totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT jiefang totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT qixu totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway
AT xiaojunwu totalflavonoidsofastragalusmembranaceusprotectagainst1methyl4phenyl1236tetrahydropyridineinducedneurotoxicityinmicebyinhibitingferroptosisthroughslc7a11gpx4signalingpathway