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Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells

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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.

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Authors and 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

    Qing Wang, Yang-yang Chen, Zhi-chao Yang, Hai-jun Yuan, Yi-wei Dong, Qiang Miao, Yan-qing Li, Jing Wang, Jie-zhong Yu, Bao-guo Xiao &  Cun-gen Ma

  2. Department of Neurology, the First Affiliated Hospital, Shanxi Medical University, Taiyuan, 030001, China

    Jing Wang

  3. Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong, Shanxi Province, 037009, China

    Jie-zhong Yu &  Cun-gen Ma

  4. Department of Neurology, Datong Fifth People’s Hospital, Datong, Shanxi Province, 037009, China

    Jie-zhong Yu

  5. Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200000, China

    Bao-guo Xiao

Authors
  1. Qing Wang
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  2. Yang-yang Chen
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  3. Zhi-chao Yang
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  7. Yan-qing Li
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  8. Jing Wang
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  11. Cun-gen Ma
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Contributions

Wang Q and Yang ZC completed most of the work together and wrote the manuscript. Ma CG and Xiao BG helped coordinate and draft the manuscript. Miao Q, Chen YY and Dong YW mainly assisted in cell experiment. Li YQ and Wang J mainly assisted in animal experiments. Yuan HJ and Yu JZ were involved in the revisions. Ma CG and Xiao BG revised and finalized the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Cun-gen Ma.

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The authors declare that they have no conflicts of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 81903596), Science and Technology Innovation Project of Shanxi Colleges (No. 2019L0728), Leading Team of Medical Science and Technology of Shanxi Province (No. 2020TD05), Funds for Construction of Key Disciplines from Shanxi University of Chinese Medicine (No. 030200117), Cultivation Project of Shanxi University of Chinese Medicine (Nos. 2019PY130 and 2020PY-JC-14)

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Wang, Q., Chen, Yy., Yang, Zc. et al. Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells. Chin. J. Integr. Med. 29, 394–404 (2023). https://doi.org/10.1007/s11655-022-3587-7

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  • DOI: https://doi.org/10.1007/s11655-022-3587-7

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