Multiple sclerosis (MS) treatment has received much attention,
yet there is still no certain cure. We herein investigate the therapeutic
effect of olean-12-en-28-ol, 3β-pentacosanoate (OPCA) on a preclinical
model of MS. First, OPCA was synthesized semisynthetically and characterized.
Then, the mice with MOG35–55-induced experimental
autoimmune/allergic encephalomyelitis (EAE) were given OPCA along
with a reference drug (FTY720). Biochemical, cellular, and molecular
analyses were performed in serum and brain tissues to measure anti-inflammatory
and neuroprotective responses. OPCA treatment protected EAE-induced
changes in mouse brains maintaining blood–brain barrier integrity
and preventing inflammation. Moreover, the protein and mRNA levels
of MS-related genes such as HLD-DR1, CCL5, TNF-α, IL6, and TGFB1
were significantly reduced in OPCA-treated mouse brains. Notably,
the expression of genes, including PLP, MBP, and MAG, involved in
the development and structure of myelin was significantly elevated
in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included
a substantial reduction in pro-inflammatory cytokines in the serum
of treated EAE animals. Lastly, following OPCA treatment, the promoter
regions for most inflammatory regulators were hypermethylated. These
data support that OPCA is a valuable and appealing candidate for human
MS treatment since OPCA not only normalizes the pro- and anti-inflammatory
immunological bias but also stimulates remyelination in EAE.
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