Abstract
Background:
Ginsenosides are main active compounds of Panax ginseng with pharmacological effects on immunological/neurological diseases. Recently, ginsenoside-Re (G-Re) has been shown to exert neuroprotective effects on neurodegenerative diseases such as Alzheimer's disease. However, whether G-Re has an effect on multiple sclerosis (MS), a representative autoimmune disease of the central nervous system (CNS), has not been revealed yet.
Purpose and methods:
The purpose of this study was to investigate pharmacological effects of G-Re and related molecular mechanisms using a myelin oligodendrocyte glycoprotein peptide-immunized experimental autoimmune encephalomyelitis (EAE) animal model of MS and lipopolysaccharide (LPS)-stimulated bEND.3 cells as an in vitro model of the blood-brain barrier (BBB).
Results:
G-Re attenuated motor impairment of EAE, demyelination, and inflammation in spinal cords of EAE mice. G-Re reduced infiltration/activation of microglia/macrophages and decreased mRNA expression levels of pro-inflammatory cytokines (IL-1β and IL-6), chemokines (MIP-1α, MCP-1, and RANTES), and enzymes (iNOS) in spinal cords of EAE mice. G-Re inhibited alterations of BBB constituents (such as astrocytes, cell adhesion molecule (platelet endothelial cell adhesion molecule-1), and tight junctional molecules (occludin and zonula occludens-1)) and toll like receptor 4 (TLR4)/MyD88/nuclear factor kappa-B (NF-κB) signaling pathways in spinal cords of EAE mice and LPS-stimulated bEND.3 cells. Interestingly, combination treatment with G-Re and TLR4 inhibitor (TAK242) significantly inhibited the upregulation of TLR4/MyD88/NF-κB pathway in LPS-stimulated bEND.3 cells. TLR4 inhibitor- and activator-treated EAE mice showed conflicting behavior patterns.
Conclusion:
G-Re might alleviate motor impairment of EAE and its pathological/inflammatory events in the spinal cord by preventing BBB disruption via downregulation of TLR4/MyD88/NF-κB signaling pathways. These findings for the first time suggest that G-Re might be a potential therapeutic for MS through maintenance of BBB integrity.
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