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.

MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization

“…In a recent study of EAE mice, CNS microglia switched toward the M2 phenotype after BSYS (a traditional Chinese medicine) treatment. Concurrently, the upregulation of miR-124, but reduction of C/EBP-α/PU.1, were observed in vivo [43]. Thus, we assumed that miR-124 supplementation reduced C/EBP-α/PU.1 signaling, which regulated the expression of inflammatory associated genes and subsequently mediated microglial activation and polarization.…”

Microglia Polarization from M1 toward M2 Phenotype Is Promoted by Astragalus Polysaccharides Mediated through Inhibition of miR‐155 in Experimental Autoimmune Encephalomyelitis

“…Related studies have shown that naringenin, an active ingredient in the traditional Chinese medicine orange-red, could regulate the M1/M2 phenotype of microglia through the MAPK signaling pathway and produced antineuritis effects [30]. Another related study showed that Bu Shen Yi Sui Capsule could alleviate neuroinflammation and demyelination by promoting microglia toward M2 polarization by regulating miR-124 and miR-155 in EAE [31]. Therefore, we speculated that the effective treatment of EAE by APS is likely to be through the regulation of microglia M1/M2 polarization phenotype.…”

Profile of the RNA in exosomes from astrocytes and microglia using deep sequencing: implications for neurodegeneration mechanisms

“…Antibody binding to the membranes was visualized by an enhanced chemiluminescence western detection system (Beyotime Biotechnology) and captured by a digital chemiluminescence scanner (C-Digit, LI-COR Biosciences, Lincoln, NE, USA). The intensities of the immunoblot bands were determined with Image Studio Version software (version 5.2, LI-COR Biosciences) (Zha et al, 2021).…”