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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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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

Show Author's information Zitian Gaoa,b,1Gaorui Wangb,1Yujie Chena,b,Wuke YuanaJun CaicAiping FengaJie FangaQi Xua( )Xiaojun Wub( )
School 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, China
Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

1 These authors contribute to the work equally.

Peer review under responsibility of Tsinghua University Press.

Abstract

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.

Keywords: Parkinson’s disease, Ferroptosis, Total flavonoids of Astragalus membranaceus, SLC7A11

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Received: 14 April 2022
Revised: 13 June 2022
Accepted: 28 July 2022
Published: 01 June 2023
Issue date: January 2024

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© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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