An Extract of Chinpi, the Dried Peel of the Citrus Fruit Unshiu, Enhances Axonal Remyelination via Promoting the Proliferation of Oligodendrocyte Progenitor Cells

Abstract

The aging-induced decrease in axonal myelination/remyelination is due to impaired recruitment and differentiation of oligodendrocyte progenitor cells (OPCs). Our previous studies have shown that a monoclonal antibody to DEAD (Asp-Glu-Ala-Asp) box polypeptide 54 (Ddx54), a member of the DEAD box family of RNA helicases, (1) specifically labels oligodendrocyte lineages, (2) binds to mRNA and protein isoforms of myelin basic proteins (MBP), and (3) regulates migration of OPCs from ventricular zone to corpus callosum in mice. It has also been demonstrated that specific loss of a 21.5 kDa MBP isoform (MBP21.5) reflects demyelination status, and oral administration of an extract of Chinpi, citrus unshiu peel, reversed the aging-induced demyelination. Here, we report that Chinpi treatment induced a specific increase in the MBP21.5, led to the reappearance of Ddx54-expressing cells in ventricular-subventricular zone and corpus callosum of aged mice, and promoted remyelination. Treatment of in vitro OPC cultures with Chinpi constituents, hesperidin plus narirutin, led to an increase in 5-bromo-2′-deoxyuridine incorporation in Ddx54-expressing OPCs, but not in NG2- or Olig2-expressing cell populations. The present study suggests that Ddx54 plays crucial role in remyelination. Furthermore, Chinpi and Chinpi-containing herbal medicines may be a therapeutic option for the aging-induced demyelination diseases.

Extracts of Immature Orange (Aurantii fructus immaturus) and Citrus Unshiu Peel (Citri unshiu pericarpium) Induce P-Glycoprotein and Cytochrome P450 3A4 Expression via Upregulation of Pregnane X Receptor

“…Flavonoids included in IO and CP have various pharmacological effects ( Tokunaga et al, 2016 ). Ethanol extracts of crude drugs include both hydrophilic and hydrophobic flavonoids.…”

“…However, a previous study reported that kampo containing IO or CP decreased the blood concentration of concomitantly administered CYP3A4 substrates via upregulation of CYP3A4 although the mechanism was unclear ( Kinoshita et al, 2011 ). IO and CP include some flavonoids that have pharmacological effects ( Tokunaga et al, 2016 ). Some flavonoids have been indicated to alter P-gp and CYP3A4 activity via changes in PXR activity ( Hiura et al, 2014 ).…”

DDX54 Plays a Cancerous Role Through Activating P65 and AKT Signaling Pathway in Colorectal Cancer

“…DDX54, a member of the DEAD-box RNA helicase protein family, has been identified as a hormone-dependent interacting protein of estrogen receptors (ERs) ( 12 ) and CAR-binding protein ( 13 ). In addition, DDX54 also had a role on DNA damage repair ( 14 ) and myelination in oligodendrocytes ( 15 ). Recently, it was reported that the association of DDX54 to SNHG10 and PBX3 led to co-stability of each other and the complex could facilitate cell growth and motility in gastric cancer ( 16 ).…”

CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4‑activated MEK/ERK and PI3K/AKT pathways

“…However, the extent and quality of endogenous remyelination is suboptimal ( 6 ). Therefore, numerous studies have aimed to promote the maturation, proliferation and differentiation of OPCs in order to improve remyelination ( 7 – 10 ). In addition, efforts have also been made to enhance oligodendrocyte replacement through cell transplantation by the authors of the present study and others ( 11 – 14 ).…”