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Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells
- Chinese Journal of Integrative Medicine Vol. 29, Issue 5, Pages: 394-404(2023)
- Affiliations：
1.Research Center of Neurobiology, the Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong, Shanxi Province (030619), China
2.Department of Neurology, the First Affiliated Hospital, Shanxi Medical University, Taiyuan (030001), China
3.Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong, Shanxi Province (037009), China
4.Department of Neurology, Datong Fifth People's Hospital, Datong, Shanxi Province (037009), China
5.Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai (200000), China
- Author bio：
Prof. MA Cun-gen, E-mail: macungen@sxtcm.edu.cn
- Funds：
DOI：10.1007/s11655-022-3587-7
CLC：Published：2023-05，
Published Online：6 January 2023，
Accepted：29 May 2022
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WANG Qing, CHEN Yang-yang, YANG Zhi-chao, et al. Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells. [J]. Chinese Journal of Integrative Medicine 29(5):394-404(2023)
WANG Qing, CHEN Yang-yang, YANG Zhi-chao, et al. Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells. [J]. Chinese Journal of Integrative Medicine 29(5):394-404(2023) DOI： 10.1007/s11655-022-3587-7.
摘要
Abstract
Objective:
2
To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.
Methods:
2
This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization
in vitro
. Based on the
in vitro
results
the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia
the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor-α (TNF-α)
interleukin-1β (IL-1β)
IL-6
IL-12
IL-17 and interferon-γ (IFN-γ) secreted by them were detected
in vitro
and
in vivo
by flow cytometry
enzyme linked immunosorbent assay (ELISA)
immunofluorescence staining and Western blot
respectively.
Results:
2
GSE reduced the secretion of TNF-α
IL-1β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (
P
<
0.01)
inhibited the secretion of TNF-α
IL-1β
IL-6
IL-12
IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (
P
<
0.05 or
P
<
0.01)
and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (
P
<
0.01). GSE significantly improved the clinical symptoms of EAE mice
and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally
GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKⅡ
P
<
0.05 or
P
<
0.01)
and inhibited the secretion of inflammatory factors (
P
<
0.01 or
P
<
0.05). In the central nervous system
GSE inhibited the infiltration of CD45
+
CD11b
+
and CD45
+
CD4
+
cells
and weakened the differentiation of Th1 and Th17 (
P
<
0.05). Moreover
it reduced the secretion of inflammatory factors (
P
<
0.01)
and prevented the activation of microglia (
P
<
0.05).
Conclusion:
2
GSE hada beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.
关键词
Keywords
grape seed extractexperimental autoimmune encephalomyelitisdemyelinationinflammatory cellinflammatory factor
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