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Ginsenoside Rg1 Plays a Neuroprotective Role in Regulating the Iron-Regulated Proteins and Against Lipid Peroxidation in Oligodendrocytes

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Progressive loss of dopaminergic neurons in the substantia nigra (SN) is one of the major pathological changes. However, the reasons for the dopaminergic neuron loss are still ambiguous and further studies are needed to evaluate the in-depth mechanisms of neuron death. Oxidative stress is a significant factor causing neuronal damage. Dopaminergic neurons in the SN are susceptible to oxidative stress, which is closely associated with iron dyshomeostasis in the brain. Ginsenoside Rg1 from ginseng plays a crucial role in neuroprotective effects through anti-inflammation and attenuating the aggregation of abnormal α-synuclein. In our study, we established a chronic PD mouse model by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine combined with probenecid and explored the effect of Rg1 on the oxidative stress and brain iron homeostasis. Rg1 was verified to improve the level of tyrosine hydroxylase and anti-oxidant stress. In addition, Rg1 maintained the iron-regulated protein homeostasis by increasing the expression of ferritin heavy chain and decreasing ferritin light chain in oligodendrocytes, especially the mature oligodendrocytes (OLs). Furthermore, Rg1 had a positive effect on the myelin sheath protection and increased the number of mature oligodendrocytes, proved by the increased staining of myelin basic protein and CC-1. In conclusion, Rg1 could play a neuroprotective role through remitting the iron-regulated protein dyshomeostasis by ferritin and against lipid peroxidation stress in oligodendrocytes.

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Enquiries about data availability should be directed to the authors.

Abbreviations

BBB:

Blood–brain barrier

BCA:

Bicinchoninic acid

BSA:

Bovine serum albumin

CNS:

Central nervous system

DA:

Dopamine

DAB:

3,3′-Diamino-benzidine

DHE:

Dihydroethidium

ECL:

Chemiluminescence

ELISA:

Enzyme-linked immunosorbent assay

FTH:

Ferritin heavy chain

FTL:

Ferritin light chain

IHC:

Immunohistochemistry

IF:

Immunofluorescence

LBs:

Lowy bodies

MAO-B:

Monoamine oxidase B

MBP:

Myelin basic protein

MPP+ :

1-Methyl-4-phenylpyridinium

MRI:

Magnetic resonance imaging

aOPCs:

Adult oligodendrocyte precursor cells

OS:

Oxidative stress

PBS:

Phosphate buffer saline

PD:

Parkinson’s disease

PVDF:

Polyvinylidene difluoride

PFA:

Paraformaldehyde

ROS:

Reactive oxygen species

SNpc:

Substantia nigra pars compacta

SPNs:

Spiny projection neurons

TEM:

Transmission electron microscopy

4-HNE:

4-Hydroxynonenal

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Acknowledgements

The authors acknowledge the support from the National Natural Science Foundation of China (81773925), the Beijing Natural Science Foundation (7212156) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-026), the Fundamental Research Funds for the Central Universities (3332019154), NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, China (2020DAMOP-008).

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  1. Ying Chen and Yan-Yan Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, I Xiannongtan Street, Xicheng District, Beijing, 100050, China

    Ying Chen, Yan-Yan Li, Shuo Wang, Tiantian Zhou, Nai-hong Chen & Yu-he Yuan

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  1. Ying Chen
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Contributions

YY and NC designed the experiments; YL and YC wrote the manuscript and prepared the figures; YC, YL and SW performed the animal model and behavior tests; YC and TZ performed western blotting assays, IHC and IF assays. All authors reviewed the manuscript.

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Correspondence to Nai-hong Chen or Yu-he Yuan.

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Chen, Y., Li, YY., Wang, S. et al. Ginsenoside Rg1 Plays a Neuroprotective Role in Regulating the Iron-Regulated Proteins and Against Lipid Peroxidation in Oligodendrocytes. Neurochem Res 47, 1721–1735 (2022). https://doi.org/10.1007/s11064-022-03564-6

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