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Bu Shen Yi Sui capsule promotes remyelination correlating with Sema3A/NRP-1, LIF/LIFR and Nkx6.2 in mice with experimental autoimmune encephalomyelitis.
- Source :
-
Journal of ethnopharmacology [J Ethnopharmacol] 2018 May 10; Vol. 217, pp. 36-48. Date of Electronic Publication: 2018 Feb 08. - Publication Year :
- 2018
-
Abstract
- Ethnopharmacological Relevance: Bu Shen Yi Sui capsule (BSYSC), based on traditional Chinese formula Liu Wei Di Huang pill, is effective for the treatment of multiple sclerosis (MS) in clinical experience and trials. Our previous studies confirmed that BSYSC had the neuroprotective effect in MS and its animal model, experimental autoimmune encephalomyelitis (EAE); however, its mechanism of action was not clear. Thus, the effect of BSYSC on remyelination and the underlying mechanisms were investigated in the EAE mice.<br />Materials and Methods: The EAE model was established by injecting subcutaneously myelin oligodendrocyte protein (MOG) <subscript>35-55</subscript> in mice. Mice were treated with BSYSC (3.02 g/kg) or vehicle daily by oral gavage for 40 days. The body weight and clinical score of mice were evaluated. Brain was observed by magnetic resonance imaging. The inflammation infiltrate of brain and spinal cord was determined by hematoxylin-eosin staining, while the structure of myelin sheath was visualized by transmission electron microscopy on days 23 and 40 post immunization (dpi), respectively. The protein and mRNA levels of platelets-derived growth factor receptor (PDGFR) α and 2', 3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) were measured by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction. The protein expressions of semaphorins (Sema) 3A, Neuropilin (NRP) - 1, leukemia inhibitory factor (LIF), LIF receptor (LIFR) and Nkx6.2 were further investigated by western blot.<br />Results: BSYSC treatment improved the body weight and clinical score of EAE mice, alleviated inflammatory infiltration and nerve fiber injuries. It also protected the ultrastructural integrity of myelin sheath. BSYSC significantly increased expressions of PDGFRα and CNPase in mice with EAE on 40 dpi. Furthermore, BSYSC treatment increased the expressions of LIF, LIFR and Nkx6.2 and reduced Sema3A and NRP-1 in EAE mice on 40 dpi.<br />Conclusions: The data demonstrated that BSYSC exhibited the neuroprotective effect against EAE by promoting oligodendrocyte progenitor cells (OPCs) proliferation and differentiation, thus facilitating remyelination. Sema3A/NRP-1, LIF/LIFR and Nkx6.2 are likely contributed to the effects of BSYSC on OPCs.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- 2',3'-Cyclic-Nucleotide Phosphodiesterases metabolism
Administration, Oral
Animals
Brain metabolism
Brain ultrastructure
Capsules
Cell Differentiation drug effects
Cell Proliferation drug effects
Drugs, Chinese Herbal administration & dosage
Encephalomyelitis, Autoimmune, Experimental chemically induced
Encephalomyelitis, Autoimmune, Experimental metabolism
Encephalomyelitis, Autoimmune, Experimental pathology
Female
Mice, Inbred C57BL
Myelin Sheath metabolism
Myelin Sheath ultrastructure
Myelin-Oligodendrocyte Glycoprotein
Neuroprotective Agents administration & dosage
Oligodendrocyte Precursor Cells drug effects
Oligodendrocyte Precursor Cells metabolism
Oligodendrocyte Precursor Cells pathology
Peptide Fragments
Receptor, Platelet-Derived Growth Factor alpha metabolism
Signal Transduction drug effects
Spinal Cord metabolism
Spinal Cord ultrastructure
Time Factors
Brain drug effects
Drugs, Chinese Herbal pharmacology
Encephalomyelitis, Autoimmune, Experimental drug therapy
Homeodomain Proteins metabolism
Leukemia Inhibitory Factor metabolism
Leukemia Inhibitory Factor Receptor alpha Subunit metabolism
Myelin Sheath drug effects
Neuropilin-1 metabolism
Neuroprotective Agents pharmacology
Semaphorin-3A metabolism
Spinal Cord drug effects
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 217
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29428242
- Full Text :
- https://doi.org/10.1016/j.jep.2018.02.014