Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells.
10.1007/s11655-022-3587-7
- Author:
Qing WANG
1
;
Yang-Yang CHEN
1
;
Zhi-Chao YANG
1
;
Hai-Jun YUAN
1
;
Yi-Wei DONG
1
;
Qiang MIAO
1
;
Yan-Qing LI
1
;
Jing WANG
1
;
Jie-Zhong YU
1
;
Bao-Guo XIAO
1
;
Cun-Gen MA
2
Author Information
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. 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. macungen@sxtcm.edu.cn.
- Publication Type:Journal Article
- Keywords:
demyelination;
experimental autoimmune encephalomyelitis;
grape seed extract;
inflammatory cell;
inflammatory factor
- MeSH:
Mice;
Animals;
Encephalomyelitis, Autoimmune, Experimental/pathology*;
Grape Seed Extract/therapeutic use*;
Interleukin-17;
Interleukin-1beta;
Tumor Necrosis Factor-alpha/metabolism*;
Interleukin-6/metabolism*;
Th1 Cells;
Mice, Inbred C57BL;
Interferon-gamma/therapeutic use*;
Th17 Cells/metabolism*;
Interleukin-12/therapeutic use*;
Cytokines/metabolism*
- From:
Chinese journal of integrative medicine
2023;29(5):394-404
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.
METHODS: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-1 β (IL-1 β), 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:GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, 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:GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.
