Abstract
The disruption of myelin causes severe neurological diseases. An understanding of the mechanism of myelination and remyelination is essential for the development of therapeutic strategies for demyelination diseases. Our previous findings indicated that the FcRγ/Fyn cascade is a potential therapeutic target for remyelination caused by the Chinese/Japanese traditional herbal (Kampo) medicine ninjin'youeito (Ninjin-youei-to, NYT), which is a hot-water extract made from 12 medicinal herbs. To identify which constituents of NYT are involved in the reversal of demyelination and to examine the potential therapeutic effect, we tested several of the chemical constituents of NYT. Here, we report that Chinpi, a constituent of NYT, upregulates the FcRγ/Fyn signaling cascade resulting in a potentially therapeutic effect against age-induced demyelination. In addition, we observed that phosphorylated (activated) FcRγ/Fyn upregulated the expression of the 21.5 kDa isoform of myelin basic protein, inducing rapid morphological differentiation, when oligodendrocyte precursor cells (OPCs) were cultured in the presence of hesperidin and/or narirutin (the major active constituents of Chinpi). These results suggest that hesperidin and narirutin participate in the FcRγ/Fyn signaling pathway in OPCs causing these cells to differentiate into myelinating oligodendrocytes.
Highlights
The myelin sheath of the central nervous system (CNS) is formed by oligodendrocytes wrapping layer upon layer of their own membranes around axons in a tight spiral, forming an electrically insulating sheath around each axon
These results suggest that hesperidin and narirutin participate in the FcRγ/Fyn signaling pathway in oligodendrocyte precursor cells (OPCs) causing these cells to differentiate into myelinating oligodendrocytes
To elucidate the active constituent herbs of NYT, which is a hot-water extract of a combination of 12 medicinal plants, the constituents of NYT were grouped into four mixtures and these mixtures were administered to elderly mice for 2 months
Summary
The myelin sheath of the central nervous system (CNS) is formed by oligodendrocytes wrapping layer upon layer of their own membranes around axons in a tight spiral, forming an electrically insulating sheath around each axon. The destruction of this myelin sheath in the CNS causes severe neurological disorders [1,2,3]. Elucidating the mechanism of demyelination/remyelination should provide new insight for future therapeutic strategies against dysmyelinating or demyelinating human diseases such as multiple sclerosis (MS), no therapy has yet been established to prevent such disease progression [4,5,6]. Further elucidation of the processes involved in OPC maturation may lead to new therapeutic strategies for MS and other related diseases [11]
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