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The therapeutic potential of bilobalide on experimental autoimmune encephalomyelitis (EAE) mice

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Abstract

Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.

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Abbreviations

CNS:

Central nervous system

MS:

Multiple sclerosis

EAE:

Experimental autoimmune encephalomyelitis

BB:

Bilobalide

NO:

Nitric oxide

PPMS:

Primary progressive multiple sclerosis

MCAO:

Middle cerebral artery occlusion

BBB:

Blood-brain barrier

CPZ:

Cuprizone

MOG:

Myelin oligodendrocyte glycolipid

p.i.:

Post-immunization

NS:

Normal saline

PFA:

Paraformaldehyde

LFB:

Luxol fast blue

H&E:

Haematoxylin/eosin

MNCs:

Mononuclear cells

MTT:

3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide

DMEM:

Dulbecco’s modified Eagle medium

DMSO:

Dimethyl sulfoxide

TLR-4:

Toll-like receptor 4

TGF-β:

Transforming growth factor β

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81473577 and 81371414), and Research Project Supported by Shanxi Scholarship Council of China (2014-7).

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Authors and Affiliations

  1. 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, Taiyuan, 030024, China

    Qiang Miao, Xiao-Xue Zhang, Qing-Xian Han, Si-Si Ren, Ruo-Xuan Sui, Qing Wang & Cun-Gen Ma

  2. Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Disease, Shanxi Datong University, Datong, 037009, China

    Jing-Wen Yu, Jie-Zhong Yu & Cun-Gen Ma

  3. The First Clinical College, Shanxi Medical University, Taiyuan, 030001, China

    Jing Wang & Cun-Gen Ma

  4. Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang, 222002, China

    Liang Cao & Wei Xiao

  5. Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200025, China

    Bao-Guo Xiao

Authors
  1. Qiang Miao
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  2. Xiao-Xue Zhang
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  12. Bao-Guo Xiao
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  13. Cun-Gen Ma
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Contributions

Cun-Gen Ma and Bao-Guo Xiao designed the experiments and checked all experimental data and analyses; Qiang Miao, Ruo-Xuan Sui, Qing-Xian Han, Si-Si Ren, and Jing Wang are involved in the establishment of the animal model and drug intervention; Xiao-Xue Zhang and Jing Wang carried out western blot; Qing Wang, Jing-Wen Yu, and Jie-Zhong Yu carried out immunohistopathology and immunohistochemistry; Liang Cao and Wei Xiao have prepared and identified bilobalide for use in this experiment.

Corresponding authors

Correspondence to Bao-Guo Xiao or Cun-Gen Ma.

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Miao, Q., Zhang, XX., Han, QX. et al. The therapeutic potential of bilobalide on experimental autoimmune encephalomyelitis (EAE) mice. Metab Brain Dis 35, 793–807 (2020). https://doi.org/10.1007/s11011-020-00555-w

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