Bu Shen Yi Sui Capsule Alleviates Neuroinflammation and Demyelination by Promoting Microglia toward M2 Polarization, Which Correlates with Changes in miR-124 and miR-155 in Experimental Autoimmune Encephalomyelitis.

Abstract

BACKGROUND:

Bu Shen Yi Sui capsule (BSYS) is a traditional Chinese medicine prescription that has shown antineuroinflammatory and neuroprotective effects in treating multiple sclerosis (MS) and its animal model of experimental autoimmune encephalomyelitis (EAE). Microglia play an important role in neuroinflammation. The M1 phenotype of microglia is involved in the proinflammatory process of the disease, while the M2 phenotype plays an anti-inflammatory role. Promoting the polarization of microglia to M2 in MS/EAE is a promising therapeutic strategy. This study is aimed at exploring the effects of BSYS on microglial polarization in mice with EAE.

METHODS:

The EAE model was established by the intraperitoneal injection of pertussis toxin and subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG)35-55 in C57BL/6J mice. The mice were treated with BSYS (3.02 g/kg), FTY720 (0.3 mg/kg), or distilled water by intragastric administration. H&E and LFB staining, transmission electron microscopy, qRT-PCR, immunofluorescence, ELISA, fluorescence in situ hybridization, and western blotting were used to detect the histological changes in myelin, microglial M1/M2 polarization markers, and the expression of key genes involved in EAE. Results and Conclusions. BSYS treatment of EAE mice increased the body weight, decreased the clinical score, and reduced demyelination induced by inflammatory infiltration. BSYS also inhibited the mRNA expression of M1 microglial markers while increasing the mRNA level of M2 markers. Additionally, BSYS led to a marked decrease in the ratio of M1 microglia (iNOS+/Iba1+) and an obvious increase in the number of M2 microglia (Arg1+/Iba1+). In the EAE mouse model, miR-124 expression was decreased, and miR-155 expression was increased, while BSYS treatment significantly reversed this effect and modulated the levels of C/EBP α, PU.1, and SOCS1 (target genes of miR-124 and miR-155). Therefore, the neuroprotective effect of BSYS against MS/EAE was related to promoting microglia toward M2 polarization, which may be correlated with changes in miR-124 and miR-155 in vivo.

• Authors: Zheng Zha, Yan-Fang Gao, Jing Ji, Ya-Qin Sun, Jun-Ling Li, Fang Qi, Nan Zhang, Liang-Yun Jin, Bing Xue, Tao Yang, Yong-Ping Fan, Hui Zhao, Lei Wang
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 5521503 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 33815654 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Zheng Zha et al.

Chemical References

• CCAAT-Enhancer-Binding Proteins
• CEBPA protein, mouse
• Capsules
• Cytokines
• Drugs, Chinese Herbal
• MicroRNAs
• Mirn124 microRNA, mouse
• Mirn155 microRNA, mouse
• Proto-Oncogene Proteins
• Trans-Activators
• bushen yisui
• proto-oncogene protein Spi-1

Topics

• Animals
• Body Weight (drug effects)
• Brain (pathology)
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Capsules
• Cell Differentiation (drug effects)
• Cell Polarity (drug effects)
• Cytokines (metabolism)
• Demyelinating Diseases (genetics)
• Drugs, Chinese Herbal (pharmacology)
• Encephalomyelitis, Autoimmune, Experimental (blood, genetics, pathology)
• Exosomes (metabolism)
• Female
• Inflammation (genetics, pathology)
• Mice, Inbred C57BL
• MicroRNAs (blood, genetics, metabolism)
• Microglia (pathology)
• Oligodendroglia (drug effects, pathology)
• Phenotype
• Proto-Oncogene Proteins (metabolism)
• Spinal Cord (pathology)
• Trans-Activators (metabolism)
• Up-Regulation (genetics)
• Mice